Conditions: Thrombocytopenia
Keywords: ITP
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 66
Healthy volunteers: no

Brief summary:
The primary objective of the study is to check if an subcutaneous (sc) infusion of UCB7665 is safe and tolerated in subjects with primary immune thrombocytopenia.

Detailed description:

Arms:
arm 1: Participants in this arm received 5 subcutaneous (sc) doses of UCB7665 (rozanolixizumab) 4 milligram per kilograms (mg/kg) at 1-week intervals. arm 2: Participants in this arm received 3 sc doses of UCB7665 (rozanolixizumab) 7 mg/kg at 1-week intervals. arm 3: Participants in this arm received 2 sc doses of UCB7665 (rozanolixizumab) 10 mg/kg at 1-week intervals. arm 4: Participants in this arm received 1 sc dose of UCB7665 (rozanolixizumab) 15 mg/kg. arm 5: Participants in this arm received 1 sc dose of UCB7665 (rozanolixizumab) 20 mg/kg.

Interventions: intervention 1: UCB7665
Intervention descriptions: intervention 1: * Intervention Type: Biological/Vaccine
* Pharmaceutical Form: Powder for solution for infusion
* Concentration: 100 mg/ml - Route of Administration:

Subcutaneous infusion

Protocol document:
Prot_000.pdf: 
UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 1 of 353
PROTOCOL TP0001 AMENDMENT 3
A MULTICENTER, OPEN-LABEL, MULTIPLE-DOSE STUDY TO 
EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF 
UCB7665 IN SUBJECTS WITH PRIMARY IMMUNE 
THROMBOCYTOPENIA
PHASE 2
EudraCT Number: 2015-003984-12
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
B-1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
09 Nov 2015
Not applicable
Protocol Amendment 1
19 May 2016
Substantial
Protocol Amendment 2 (not 
implemented)
21 Oct 2016
Substantial –
Not 
implemented
Protocol Amendment 3
15 Feb 2017
Substantial
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 2 of 353
STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60
B-1070 Brussels
BELGIUM
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporation Drive, Suite 175
Raleigh
NC 27617, USA
Phone:
Fax:
Clinical Project Manager
Name:
Address:
UCB BioSciences GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Clinical Trial Biostatistician
Name:
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Straße 10
40789 Monheim 
GERMANY
Phone:
Fax:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 3 of 353
Clinical Monitoring Contract Research Organization
Name:
PAREXEL International GmbH
Address:
Early Product Development
Spandauer Damm 130
D-14050 Berlin
GERMANY
Phone:
+49 (0) 30 30 685 0
Fax:
+49 (0) 30 30 685 7113
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 4 of 353
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 65 61
Email
Global: safetyreportingUCB7665@ucb.com
REDACTED COPY 
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or


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 5 of 353
TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................12
1
SUMMARY.....................................................................................................................15
2
INTRODUCTION ...........................................................................................................18
3
STUDY OBJECTIVE(S).................................................................................................20
3.1 Primary objective.............................................................................................................20
3.2 Secondary objectives .......................................................................................................20
3.3 Exploratory objectives .....................................................................................................20
4
STUDY VARIABLES.....................................................................................................21
4.1 Primary variable...............................................................................................................21
4.2 Others and exploratory variables .....................................................................................21
4.2.1
Safety variables....................................................................................................21
4.2.2
Efficacy variables ................................................................................................21
4.2.3
Pharmacokinetic variable.....................................................................................22
4.2.4
Pharmacodynamic variables ................................................................................23
4.2.5
Other immunological variables............................................................................23
5
STUDY DESIGN.............................................................................................................23
5.1 Study description .............................................................................................................23
5.1.1
Exploratory genomic analyses.............................................................................25
5.1.2
Study duration per subject ...................................................................................26
5.1.3
Planned number of subjects and sites ..................................................................26
5.1.4
Anticipated regions and countries .......................................................................26
5.2 Schedule of study assessments.........................................................................................26
5.3 Schematic diagram...........................................................................................................55
5.4 Rationale for study design and selection of dose.............................................................56
5.4.1
Pathophysiology of ITP .......................................................................................56
5.4.2
Mechanism of action of UCB7665......................................................................56
5.4.3
Choice of study design and endpoints .................................................................56
5.4.4
Safety of UCB7665..............................................................................................56
5.4.5
Rationale for dose selection.................................................................................57
5.4.6
Justification for additional genomic analyses......................................................58
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................58
6.1 Inclusion criteria ..............................................................................................................58
6.2 Exclusion criteria .............................................................................................................60
6.2.1
Exclusion criteria related to health status ............................................................60
6.2.2
Exclusion criteria related to medical history .......................................................61
6.2.3
Exclusion criteria related to concomitant medications/procedures .....................62
6.3 Rescreening......................................................................................................................64
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
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6.4 Withdrawal criteria ..........................................................................................................64
6.4.1
Potential drug induced liver injury IMP discontinuation criteria ........................65
6.5 Study stopping rules.........................................................................................................66
7
STUDY TREATMENT...................................................................................................66
7.1 Description of investigational medicinal product............................................................66
7.2 Treatment to be administered...........................................................................................67
7.3 Packaging.........................................................................................................................67
7.4 Labeling ...........................................................................................................................67
7.5 Handling and storage requirements..................................................................................67
7.6 Drug accountability..........................................................................................................68
7.7 Procedures for monitoring subject compliance................................................................68
7.8 Concomitant medication/treatment..................................................................................68
7.8.1
Permitted immunosuppressant medications ........................................................68
7.8.2
Prohibited concomitant treatments (medications and therapies).........................69
7.8.3
Rescue medication...............................................................................................70
7.9 Blinding............................................................................................................................70
7.10 Randomization and numbering of subjects......................................................................70
8
STUDY PROCEDURES BY VISIT ...............................................................................70
8.1 Screening Period ..............................................................................................................71
8.1.1
Visit 1 (Day -28 to -1) Screening Visit (all Dose Arms).....................................71
8.2 Dosing Period for all Dose Arms.....................................................................................72
8.2.1
Visit 2 (Week 1/Day 1) Baseline Visit ................................................................72
8.2.2
Visit 3 (Week 1/Day 4) [UCB7665 4mg/kg, UCB7665 7mg/kg, and UCB7665 
10mg/kg]..............................................................................................................74
8.2.3
Visit 4 (Week 2/Day 8) [UCB7665 4mg/kg, UCB7665 7mg/kg and UCB7665 
10mg/kg]..............................................................................................................74
8.2.4
Visit 5 (Week 3/Day 15) [UCB7665 4mg/kg and UCB7665 7mg/kg] ...............76
8.2.5
Visit 6 for Dose Arm 1 (Week 4/Day 22) [UCB7665 4mg/kg only] ..................77
8.2.6
Visit 7 for Dose Arm 1 (Week 5/Day 29) [UCB7665 4mg/kg only] ..................78
8.3 Telephone Contacts..........................................................................................................79
8.3.1
Telephone Contact 1 (Week 1/Day 2) [UCB7665 10mg/kg, UCB7665 15mg/kg, 
UCB7665 20mg/kg].............................................................................................79
8.3.2
Telephone Contact 2 (Week 1/Day 3) [UCB7665 10mg/kg, UCB7665 15mg/kg, 
UCB7665 20mg/kg].............................................................................................79
8.3.3
Telephone Contact 3 (Week 2/Day 9) [UCB7665 10mg/kg only]......................80
8.3.4
Telephone Contact 4 (Week 2/Day 10) [UCB7665 10mg/kg only]....................80
8.4 Observation Period...........................................................................................................80
8.4.1
Visit 8 (Week 5/Day 32) [UCB7665 4mg/kg]/ 
Visit 6 (Week 3/Day 18) [UCB7665 7mg/kg]/ Visit 5 (Week 2/Day 11) 
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 7 of 353
[UCB7665 10mg/kg] Visit 3 (Week 1/Day 4) [UCB7665 15mg/kg and 
UCB7665 20mg/kg].............................................................................................80
8.4.2
Visit 9 (Week 6/Day 36) [UCB7665 4mg/kg ]/ 
Visit 7 (Week 4/Day 22) [UCB7665 7mg/kg]/ 
Visit 6 (Week 3/Day 15) [UCB7665 10mg/kg] Visit 4 (Week 2/Day
8) [UCB7665 15mg/kg and UCB7665 20mg/kg]................................................81
8.4.3
Visit 10 (Week 7/Day 43) [UCB7665 4mg/kg]/ 
Visit 8 (Week 5/Day 29) [UCB7665 7mg/kg]/ 
Visit 7 (Week 4/Day 22) [UCB7665 10mg/kg] Visit 5 (Week 3/Day
15) [UCB7665 15mg/kg and UCB7665 20mg/kg]..............................................82
8.4.4
Visit 11 (Week 8/Day 50) [UCB7665 4mg/kg]/ 
Visit 9 (Week 6/Day 36) [UCB7665 7mg/kg]/ 
Visit 8 (Week 5/Day 29) [UCB7665 10mg/kg] Visit 6 (Week 4/Day
22) [UCB7665 15mg/kg and UCB7665 20mg/kg]..............................................83
8.4.5
Visit 12 (Week 9/Day 57) [UCB7665 4mg/kg]/ 
Visit 10 (Week 7/Day 43) [UCB7665 7mg/kg]/ 
Visit 9 (Week 6/Day 36) [UCB7665 10mg/kg] Visit 7 (Week 5/Day
29) [UCB7665 15mg/kg and UCB7665 20mg/kg]..............................................84
8.4.6
Visit 13 (Week 10/Day 64) [UCB7665 4mg/kg]/ 
Visit 11 (Week 8/Day 50) [UCB7665 7mg/kg]/ 
Visit 10 (Week 7/Day 43) [UCB7665 10mg/kg] Visit 8 (Week 6/Day
36) [UCB7665 15mg/kg and UCB7665 20mg/kg]..............................................85
8.4.7
Visit 14 (Week 11/Day 71) [UCB7665 4mg/kg]/ 
Visit 12 (Week 9/Day 57) [UCB7665 7mg/kg]/ 
Visit 11 (Week 8/Day 50) [UCB7665 10mg/kg] Visit 9 (Week 7/Day
43) [UCB7665 15mg/kg and UCB7665 20mg/kg]..............................................86
8.4.8
End-of-Study Visit: Visit 15 (Week 13/Day 85) [UCB7665 4mg/kg]/ 
Visit 13 (Week 11/Day 71) [UCB7665 7mg/kg]/ 
Visit 12 (Week 10/Day 64) [UCB7665 10mg/kg] Visit 10 (Week 9/Day
57) [UCB7665 15mg/kg and UCB7665 20mg/kg]..............................................87
8.5 Early Withdrawal Visit ....................................................................................................88
8.6 Unscheduled Visit............................................................................................................88
9
ASSESSMENT OF EFFICACY......................................................................................88
9.1 Platelet counts ..................................................................................................................88
9.2 ITP bleeding score ...........................................................................................................90
9.3 Patient reported outcomes................................................................................................90
9.3.1
NFI-MS................................................................................................................90
9.4 Subject exit interview ......................................................................................................91
10
ASSESSMENT OF PHARMACOKINETIC/ PHARMACODYNAMIC VARIABLES91
10.1 Pharmacokinetic variables ...............................................................................................91
10.2 Pharmacodynamic variables ............................................................................................91
11
ASSESSMENT OF OTHER IMMUNOLOGICAL VARIABLES.................................91
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UCB7665
TP0001
Confidential
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12
ASSESSMENT OF SAFETY..........................................................................................92
12.1 Adverse events.................................................................................................................92
12.1.1
Definition of adverse event..................................................................................92
12.1.2
Procedures for reporting and recording adverse events.......................................93
12.1.3
Description of adverse events..............................................................................93
12.1.4
Follow up of adverse events ................................................................................93
12.1.5
Rule for repetition of an adverse event................................................................93
12.1.6
Pregnancy ............................................................................................................94
12.1.7
Suspected transmission of an infectious agent via a medicinal product..............95
12.1.8
Overdose of investigational medicinal product ...................................................95
12.1.9
Safety signal detection.........................................................................................95
12.1.10
Hypersensitivity and adverse reactions ...............................................................95
12.1.11
Management of severe headache.........................................................................96
12.1.12
Management of moderate or severe diarrhea.......................................................96
12.2 Serious adverse events .....................................................................................................96
12.2.1
Definition of serious adverse event .....................................................................96
12.2.2
Procedures for reporting serious adverse events .................................................97
12.2.3
Follow up of serious adverse events....................................................................98
12.3 Adverse events of special interest....................................................................................98
12.4 Adverse events of interest................................................................................................98
12.5 Immediate reporting of adverse events............................................................................99
12.6 Anticipated serious adverse events ..................................................................................99
12.7 Laboratory measurements................................................................................................99
12.7.1
Evaluation of PDILI ..........................................................................................101
12.7.1.1
Consultation with Medical Monitor and local hepatologist ....................104
12.7.1.2
Immediate action: determination of IMP discontinuation.......................104
12.7.1.3
Testing: identification/exclusion of alternative etiology.........................105
12.7.1.4
Follow-up evaluation...............................................................................106
12.8 Other safety measurements............................................................................................106
12.8.1
Assessment and management of TB and TB risk factors..................................106
12.8.1.1
TB Tests at Screening..............................................................................107
12.8.1.2
Monitoring for TB during the study........................................................107
12.8.1.3
TB tests at Final /End of Study Visit.......................................................107
12.8.1.4
Signs and symptoms of Tuberculosis......................................................107
12.8.2
Pregnancy testing...............................................................................................108
12.8.3
Vital signs ..........................................................................................................108
12.8.4
Body weight and height.....................................................................................109
12.8.5
Physical examination.........................................................................................109
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TP0001
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12.8.6
12-Lead ECG.....................................................................................................110
13
STUDY MANAGEMENT AND ADMINISTRATION...............................................110
13.1 Adherence to protocol....................................................................................................110
13.2 Monitoring .....................................................................................................................110
13.2.1
Definition of source data ...................................................................................111
13.2.2
Source data verification .....................................................................................111
13.3 Data handling.................................................................................................................111
13.3.1
Case Report form completion............................................................................111
13.3.2
Database entry and reconciliation......................................................................112
13.3.3
Subject Screening and Enrollment log/Subject Identification Code list............112
13.4 Termination of the study................................................................................................112
13.5 Archiving and data retention..........................................................................................112
13.6 Audit and inspection ......................................................................................................113
13.7 Good Clinical Practice ...................................................................................................113
14
STATISTICS .................................................................................................................113
14.1 Definition of analysis sets..............................................................................................113
14.2 General statistical considerations...................................................................................114
14.3 Planned safety analyses..................................................................................................114
14.3.1
Analysis of the primary safety variable.............................................................114
14.3.2
Other safety analyses .........................................................................................115
14.4 Planned efficacy and other analyses ..............................................................................115
14.4.1
Efficacy analyses ...............................................................................................115
14.4.2
Pharmacokinetic analyses..................................................................................116
14.4.3
Pharmacodynamic analyses...............................................................................116
14.4.4
Immunologic variables ......................................................................................117
14.4.5
Other analyses....................................................................................................117
14.4.5.1
Subject disposition ..................................................................................117
14.4.5.2
Subject characteristics .............................................................................117
14.4.5.3
Baseline disease characteristics...............................................................117
14.4.5.4
Subject exit interview..............................................................................117
14.5 Handling of protocol deviations.....................................................................................117
14.6 Handling of dropouts or missing data............................................................................118
14.7 Planned interim analysis and data monitoring...............................................................118
14.8 Determination of sample size.........................................................................................119
15
ETHICS AND REGULATORY REQUIREMENTS....................................................120
15.1 Informed consent ...........................................................................................................120
15.2 Subject identification cards............................................................................................120
15.3 Institutional Review Boards and Independent Ethics Committees................................120
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
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Page 10 of 353
15.4 Subject privacy...............................................................................................................121
15.5 Protocol amendments.....................................................................................................122
16
FINANCE, INSURANCE, AND PUBLICATION.......................................................122
17
REFERENCES ..............................................................................................................122
18
APPENDICES ...............................................................................................................124
18.1 Karnofsky Performance Status Scale.............................................................................124
18.2 ITP – Bleeding Assessment Tool (ITP-BAT)................................................................125
18.3 Neurological Fatigue Index for Multiple Sclerosis (NFI-MS) ......................................135
18.4 Suggested management guidelines for infusion reactions.............................................137
18.5 Diagnosis of anaphylactic reactions...............................................................................138
18.6 Headache Questionnaire ................................................................................................139
18.7 Protocol Amendment 1 ..................................................................................................143
18.8 Protocol Amendment 2 (not implemented)....................................................................185
18.9 Protocol Amendment 3 ..................................................................................................247
19
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................352
20
SPONSOR DECLARATION ........................................................................................353
LIST OF TABLES
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm 
(Dose Arm 1) ...................................................................................................27
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm 
(Dose Arm 2) ...................................................................................................33
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose 
arm (Dose Arm 3)............................................................................................38
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose 
Arm 4)..............................................................................................................43
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose 
Arm 5)..............................................................................................................48
Table 5‒6:
Schedule of investigations on the dosing days ................................................53
Table 6‒1:
Washout periods for immunosuppressants, biologics and other therapies ......63
Table 7‒1:
Permitted immunosuppressant medications.....................................................69
Table 12‒1: Anticipated serious adverse events for ITP population.......................................99
Table 12‒2: Laboratory measurements..................................................................................100
Table 12-3: Required investigations and follow up for PDILI..............................................102
Table 12-4:
PDILI laboratory measurements....................................................................105
Table 12-5: PDILI information to be collected......................................................................106
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Clinical Study Protocol
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Table 18‒1: Karnofsky Performance Status Scale Definitions Rating (%) Criteria..............124
Table 18‒2: ITP-Bleeding Assessment Tool.........................................................................125
Table 18‒3: Reporting of bleeding after hemostatic challenges or surgery°.........................134
Table 18‒4: NFI-MS..............................................................................................................135
Table 18‒5: Suggested management guidelines for infusion reactions.................................137
Table 18‒6: Headache Questionnaire ....................................................................................139
LIST OF FIGURES
Figure 5‒1:
Schematic diagram...........................................................................................55
REDACTED COPY 
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Clinical Study Protocol
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TP0001
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Page 12 of 353
LIST OF ABBREVIATIONS
ADA
anti-drug antibodies 
ADL
activities of daily living
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUEC
area under the effect curve
BAFF
B cell activating factor
BP
blood pressure
CDMS
clinical data management system
CHMP
Committee for Medicinal Products for Human Use
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRO
contract research organization
CSF
cerebrospinal fluid 
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DCP
Data Cleaning Plan
DNA
deoxyribonucleic acid
DMC
Data Monitoring Committee
ECG
electrocardiogram
EDC
electronic data capture
EMA
European Medicines Agency
eCRF
electronic Case Report form
ES
Enrolled Set
EOS
End of Study
FAS
Full Analysis Set
FcRn
neonatal Fc receptor for IgG
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 13 of 353
HbA1c
glycosylated hemoglobin 
HIV
human immunodeficiency virus
HLA
human leukocyte antigen
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
Ig
immunoglobulin 
IGRA
interferon-gamma release assay
IMP
investigational medicinal product
INR
International Normalized Ratio
IRB
Institutional Review Board
ITP
immune thrombocytopenia 
ITP-BAT
ITP-specific Bleeding Assessment Tool
iv
intravenous
IVIg
intravenous immunoglobulin
IXRS
interactive voice/web response system
LTB
latent tuberculosis
LLOQ
lower limit of quantification
LP
lumbar puncture 
MCID
minimal clinically important difference
MedDRA
Medical Dictionary for Regulatory Activities
MHC
major histocompatibility complex
MRI
magnetic resonance imaging
mRNA
messenger ribonucleic acid
miRNA
micro ribonucleic acid
NFI-MS
Neurological Fatigue Index for Multiple Sclerosis
NTMBI
nontuberculosis myobacterial infection
NOAEL
no observed adverse effect level 
PD
pharmacodynamic(s)
PDILI
potential drug-induced liver injury
PD-PPS
Pharmacodynamic Per Protocol Set
PEF
peak expiratory flow
PK
pharmacokinetic(s)
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UCB7665
TP0001
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PK-PPS
Pharmacokinetic Per Protocol Set
PLEX
plasma exchange
PPS
Per Protocol Set
PRO
Patient Reported Outcome
PS
Patient Safety
PTT
partial thromboplastin time
QTc
corrected QT interval
RNA
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous
SD
standard deviation
SMOG
skin (S), visible mucosae (M), and organs (O), with gradation of severity
SOP
Standard Operating Procedure
SS
Safety Set
TB
tuberculosis
TEAE
treatment-emergent adverse event
TPO-R
thrombopoietin-receptor
ULN
upper limit of normal 
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1
SUMMARY
Primary immune thrombocytopenia (ITP) is a disease which is characterized by an isolated low 
platelet count (thrombocytopenia) and the absence of other causes of thrombocytopenia. It is an 
autoimmune disease which is characterized by specific autoantibodies directed against platelets. 
There is no causal treatment. Treatment options include immunosuppressive therapy, 
immunoglobulin therapy, and splenectomy. There is an unmet medical need for new treatment 
options due to significant side effects, significant risks, and significant complexity of existing
therapy.
The neonatal major histocompatibility complex (MHC)-class-I-like neonatal Fc receptor for IgG 
(FcRn) binds immunoglobulin G (IgG), thereby preventing IgG from intracellular lysosomal 
degradation. UCB7665 is a humanized IgG4 monoclonal antibody that has been specifically 
designed to inhibit IgG binding to FcRn with the aim to reduce the concentration of pathogenic 
IgG in patients with IgG autoantibody mediated diseases, including ITP. Thereby, it represents a 
potential new mode of action to target the underlying pathomechanism of ITP and could enhance 
the still limited treatment options.
TP0001 is a Phase 2, multicenter, open-label, multiple-dose, multiple-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 administered as subcutaneous (sc) doses of 
4mg/kg, 7mg/kg, 10mg/kg, 15mg/kg, and 20mg/kg (resulting in cumulative doses of 20mg/kg, 
21mg/kg, 20mg/kg, 15 mg/kg and 20mg/kg respectively), in subjects ≥18 years of age with 
persistent (>3 months up to 12 months after diagnosis) or chronic (more than 12 months after
diagnosis) primary ITP. 
The study is planned to be conducted at up to approximately 45 sites in Europe and Australia. A 
total of approximately 48 to 66 subjects (dependent on emerging safety data and corresponding 
DMC recommendation) are planned to enter the Dosing Period in the study. The maximum study
duration for study participation for an individual subject is approximately 16 weeks.
The study is intended to evaluate 5 dose arms of UCB7665. Subjects in Dose Arm 1 will receive 
5 doses of UCB7665 4mg/kg sc at 1 week intervals, subjects in Dose Arm 2 will receive 3 doses 
of UCB7665 7mg/kg sc at 1 week intervals, subjects in Dose Arm 3 will receive 2 doses of 
UCB7665 10mg/kg sc at 1 week intervals, Dose Arm 4 will receive 1 dose of UCB7665
15mg/kg sc and Dose Arm 5 will receive 1 dose of UCB7665 20mg/kg sc.
The study consists of a Screening Period (up to 4 weeks), Dosing Period of 1 day to 4 weeks
where dosing arms are introduced sequentially, and an Observation Period of 8 weeks. The 
Screening Visit corresponds to Visit 1 of the study. The Dosing Period will commence at Visit 2
(Baseline Visit), with dosing visits scheduled at weekly intervals for Dose Arms 1, 2 and 3 and
only one visit scheduled for Dose Arms 4 and 5. The Observation Period will start after the last
dose administration (or only dose administration for Dose Arms 4 and 5) with a visit scheduled 3 
days after the last dosing and weekly visits thereafter (ie, weekly after last or only dose) for a 
period of 8 weeks. The End-of-Study Visit will be performed at the end of the Observation 
Period, ie, 8 weeks after the last or only dose of investigational medicinal product (IMP).
The first 6 subjects will be enrolled in Dose Arm 1 only. While recruitment is ongoing, safety
data for the first 3 subjects up to 7 days after the last dose of the third subject will be reviewed by 
the Data Monitoring Committee (DMC). During a second DMC meeting, all available safety 
data up to cut off date defined as 7 days after the last dose of the sixth subject will be reviewed. 
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UCB
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Clinical Study Protocol
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TP0001
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Following this review, the DMC will make a recommendation on whether to open Dose Arm 2 
for enrollment. Once the DMC has advocated the initiation of Dose Arm 2, the subsequent 
subjects for the first 2 arms will be randomly assigned in 1:1 ratio to either Dose Arm 1 or Dose 
Arm 2 using an interactive voice/web response system (IXRS). Once 15 subjects are enrolled in 
Dose Arm 1, the subsequently enrolled subjects will be enrolled in Dose Arm 2.
After the safety data review of at least 6 subjects in Dose Arm 2 is done, the DMC will make a 
recommendation on whether to open Dose Arm 3 for enrollment. Once the DMC has advocated
the initiation of Dose Arm 3 and the enrollment of 15 subjects into Dose Arm 2 has been 
completed, the subsequent subjects will be assigned to Dose Arm 3 only. After every third 
subject has been enrolled, DMC will review all available safety data up to cut off date defined as 
7 days after the last dose of the respective subject. Depending on the emerging safety data of 
6 subjects in Dose Arm 3, the DMC will recommend whether to open Dose Arm 4 for enrollment 
or to include additional subjects in Dose Arm 3. If applicable, this procedure is planned to be 
repeated stepwise in groups of 3 subjects. A maximum of 12 subjects are planned for Dose Arm 
3. The DMC will recommend to open Dose Arm 4 for enrollment in a subsequent DMC meeting, 
if applicable.
Once the DMC has advocated the initiation of Dose Arm 4, the enrollment of Dose Arm 3 will 
be closed and all subsequently enrolled subjects will be assigned to Dose Arm 4. After every
third subject that has been enrolled, DMC will review all available safety data up to cut off date 
defined as 7 days after the last dose of the respective subject. Depending on the emerging safety 
data of 6 subjects in Dose Arm 4, the DMC will recommend whether to open Dose Arm 5 for 
enrollment or to include additional subjects in Dose Arm 4. If applicable, this procedure is 
planned to be repeated stepwise in groups of 3 subjects. A maximum of 12 subjects are planned 
for Dose Arm 4. The DMC will recommend to open Dose Arm 5 for enrollment in a subsequent 
meeting, if applicable.
Once the DMC has advocated the initiation of Dose Arm 5, the enrollment of Dose Arm 4 will 
be closed and the subsequently enrolled subjects will be assigned to Dose Arm 5. After every
third subject is enrolled, the DMC will review all available safety data up to the cutoff date 
defined as 7 days after the dosing of the third subject in Dose Arm 4. Depending on the emerging 
safety data of 6 subjects in Dose Arm 5, the DMC will recommend to include additional subjects 
in Dose Arm 5. If applicable, this procedure is planned to be done stepwise in groups of 
3 subjects. A maximum of 12 subjects may be enrolled in Dose Arm 5.
The DMC may also decide to reduce the number of doses dose arms, to stop a dose arm or not to 
open a dose arm based on review of safety data during the study. Safety data will also be 
reviewed on an ongoing basis by clinical research organization (CRO) medical monitor and UCB 
physician during the study so as to continuously evaluate the safety of subjects.
The primary objective of the study is to evaluate the safety and tolerability of UCB7665 
administered by sc infusion in subjects with ITP. 
The secondary objective of the study is to assess the clinical efficacy of UCB7665 as measured 
by the change in platelet count and to assess the pharmacodynamic (PD) effect of UCB7665 as 
measured by the change in total IgG concentrations in serum. The exploratory objectives include 
the following:
to evaluate the clinical efficacy as measured by 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 17 of 353
the change in ITP bleeding score; to evaluate the effect of UCB7665 on the concentrations of 
total protein, albumin, α-globulin and β-globulin, IgG subclasses, IgM, IgA, and IgE, and serum
and plasma complement levels; to evaluate the emergence of anti-drug antibodies (ADA), ie, 
anti-UCB7665 antibodies with respect to immunogenicity and pharmacokinetics (PK)/PD; to 
evaluate the relationship between changes in platelet count and total IgG, IgG subclasses, 
ITP-specific autoantibodies; and to assess the plasma concentrations of UCB7665 administered 
by sc infusion.
The primary safety variable is the occurrence of treatment-emergent adverse events (TEAEs). 
Other safety variables are TEAEs leading to withdrawal of IMP, vital signs, 12-lead 
electrocardiogram (ECG), laboratory parameters (hematology including coagulation parameters, 
clinical chemistry, and urinalysis), and concentrations of total protein, albumin, α-globulin, and 
β-globulin in serum. 
Other safety assessments are evaluation of potential drug-induced liver injury (PDILI), using 
pre-specified criteria for managing any PDILI events in accordance with the Drug 
Administration (FDA) Guidance for Industry, Drug-Induced Liver Injury: Premarketing Clinical 
Evaluation (Jul 2009).
The following efficacy variables will be assessed: Response (platelet count ≥30x109/L and at 
least 2-fold increase of the Baseline count) during the study and by visit; Complete Response
(platelet count ≥100x109/L) during the study and by visit; platelet count ≥50x109/L during the 
study and by visit; the maximum value and maximum increase from Baseline in platelet count 
during the study; value and change from Baseline in platelet count over time; Baseline-corrected 
area under the effect curve (AUEC) for platelet count; time to Response (time from starting 
treatment to achievement of Response); time to Complete Response (time from starting treatment 
to achievement of Complete Response); time to achieving platelet count ≥50x109/L; duration of 
Response (measured from achievement of Response to loss of Response [defined as platelet 
count below 30x109/L or less than 2-fold increase of Baseline platelet count]); duration of 
Complete Response (measured from achievement of Complete Response to loss of Complete 
Response [defined as platelet count below 100x109/L]); duration of platelet count ≥50x109/L
(measured from achievement of platelet count ≥50x109/L to reduction of platelet count below 
50x109/L); Clinical Response (defined as platelet count ≥30x109/L and at least 2-fold increase 
from Baseline value and absence of bleeding); time to Clinical Response (time from starting 
treatment to achievement of Clinical Response); duration of Clinical Response (measured from 
achievement of Clinical Response to loss of Clinical Response [loss of Clinical Response 
defined as platelet count <30x109/L or less than 2-fold increase from Baseline platelet count or 
presence of bleeding]); Complete Clinical Response (defined as platelet count ≥100x109/L and 
absence of bleeding); time to Complete Clinical Response (time from starting treatment to 
achievement of Complete Clinical Response); duration of Complete Clinical Response 
(measured from achievement of Complete Clinical Response to loss of Complete Clinical 
Response [loss of Complete Clinical Response defined as platelet count <100x109/L or presence 
of bleeding]); no Clinical Response (defined as platelet count <30x109/L and less than 2-fold 
increase from Baseline or presence of bleeding); ITP bleeding score over time; and Patient 
Reported Outcome (PRO), ie, Neurological Fatigue Index for Multiple Sclerosis (NFI-MS) 
summary score over time. Plasma concentration of UCB7665 over time will be assessed as the 
PK variable. The PD variables are minimum value and maximum decrease in total IgG
concentration during the study; IgG subclass concentrations; and ITP-specific autoantibody 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 18 of 353
in serum over time. Other immunological variables to be 
evaluated are total IgA, IgE, and IgM levels; serum (C3 and C4) and plasma (C3a and C5a)
complement levels; ADA status (negative/positive) and relative mass units; exploratory safety
biomarkers
and B cell activating 
factor (BAFF) levels; B and T lymphocytes; and cytokines (for subjects experiencing infusion
reactions).
During this study, subjects will also have the option of providing additional informed consent for 
exploratory deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) (ie, messenger RNA 
[mRNA] and micro RNA [miRNA]) analyses. Participation in this additional portion of the study
is optional and does not preclude subject’s eligibility for participation in the main study. The 
additional genomic samples must not be collected if the subject has not consented to participate 
in this exploratory genomic substudy.
Prior to this amendment, a protocol amendment 2 with a dose arm 4mg/kg twice weekly was 
planned, however the corresponding protocol amendment 2 was not implemented. These changes 
are highlighted in Section 18.8.
2
INTRODUCTION
The neonatal MHC-class-I-like FcRn recycles immunoglobulin and albumin from most cells and 
transports it bi-directionally across epithelial barriers to affect systemic and mucosal immunity. 
It was shown that FcRn rescues both IgG and albumin from intracellular lysosomal degradation 
by recycling it from the sorting endosome to the cell surface (Anderson et al, 2006). With respect 
to IgG, this is achieved by interaction of IgG with the receptor, FcRn. Thus, in effect FcRn 
salvages IgG, saving it from degradation and returning it to circulation. Albumin is similarly
recycled by FcRn, though via a different binding site on the FcRn molecule. It has been shown 
that knockout or blockade of FcRn removes this recycling resulting in endosomal catabolism of 
IgG and a marked reduction of IgG concentrations in both the vascular and extravascular (tissue) 
compartments. In effect, blockade of FcRn accelerates removal of endogenous IgG and, if the 
albumin binding site is also blocked, potentially of albumin. 
Immune thrombocytopenia is a clinical disorder in which thrombocytopenia manifests as a 
bleeding tendency, purpura, or petechiae. Autoantibodies against platelet antigens are considered 
to be a hallmark of ITP. Production of pathogenic IgG autoantibodies by plasma cells is accepted 
as the central underlying pathophysiological mechanism in a number of IgG-mediated 
autoimmune diseases, which includes ITP. In some patients, antibodies recognize antigens 
derived from a single glycoprotein, whereas in others, antibodies recognize multiple 
glycoproteins. The spleen is the key organ in the pathophysiology of ITP, not only because 
platelet autoantibodies are formed in the white pulp, but also because mononuclear macrophages 
in the red pulp destroy immunoglobulin-coated platelets (Sandler, 2000).
Recently, new definitions for the phases of the disease were introduced (Rodeghiero et al, 2009). 
Based on the time from diagnosis, the first phase (up to 3 months) is the “newly-diagnosed ITP,” 
phase 2 (>3 months up to 12 months) is the “persistent phase,” and after 12 months the “chronic 
phase” starts. These phases also reflect the line of treatment.
The major goal for treatment of ITP is to achieve a platelet count that prevents major bleeding 
rather than correcting the platelet count to normal levels. The management of ITP should be 
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tailored to the individual patient and it is rarely indicated in those with platelet counts above 
50x109/L in the absence of bleeding, trauma, surgery, or high risk factors (eg, patients on 
anticoagulation therapy) (EMA/CHMP/153191/2013, 2014). However, there is general 
agreement that adults with a count of <30x109/L with bleeding at diagnosis require treatment. 
The first line of treatment for newly-diagnosed ITP is generally agreed and based on the use of 
corticosteroids and intravenous immunoglobulin (IVIg). Patients who fail to respond or who 
relapse face the options of treatment with second line drug therapy or splenectomy but there is no 
clear evidence to support the best approach. Splenectomy can provide long-term efficacy in 
around 60% of cases and recent guidelines suggest considering a splenectomy after 12 months. 
Splenectomy is an invasive procedure associated with acute complications due to 
thrombocytopenia (like bleeding events) and long-term complications from loss of splenic 
functions. Asplenic subjects are at increased risk of life-threatening infections. Splenectomy may
increase morbidity from venous thromboembolism or atherosclerosis (Ghanima et al, 2012). 
Second line drug therapies include high-dose dexamethasone or methylprednisolone; high-dose 
IVIg or anti-D Ig; vinca alkaloids; dapsone and danazol; the immunosuppressants 
cyclophosphamide, azathioprine, and cyclosporine; or mycophenolate mofetil and Helicobacter 
pylori eradication if applicable. The anti-CD20 monoclonal antibody rituximab - even if not 
licensed for the treatment of ITP - and the thrombopoietin-receptor (TPO-R) agonists are 
considered as second line as well as third line options.
Treatment-related morbidity is also a significant contributing factor; long-term courses of 
corticosteroids, other immunosuppressive medications, or splenectomy may be required to 
maintain a platelet count in a safe range in patients with chronic treatment-resistant ITP and 
morbidity and mortality can be related to treatment, reflecting the complications of therapy with 
corticosteroids or splenectomy. There thus remains a considerable unmet medical need for new 
therapeutic options in the treatment of ITP. UCB7665 may become the first targeted therapy to 
remove the autoantibodies to platelets providing a safe and tolerable alternative for patients with 
persistent or chronic ITP in acute or maintenance therapy.
UCB7665 is a humanized anti-FcRn monoclonal antibody that has been specifically designed to 
inhibit IgG binding to FcRn without inhibiting albumin binding to FcRn. UCB7665 is being 
developed as an inhibitor of FcRn activity with the aim to reduce the concentration of pathogenic 
IgG in patients with IgG autoantibody mediated diseases. UCB7665 was derived from a rat 
antibody with specificity for human FcRn by engineering the rat antibody into a humanized 
IgG4P format. The construct encoding UCB7665 was created by grafting the 
complementarity-determining region (CDRs) from the parental rat heavy and light chain variable 
regions onto a human IgG4P and kappa chain genetic background, respectively. The resulting 
UCB7665 contains only the original rat sequences that comprise the antigen binding site; all 
other sequences are human in origin.
UCB7665 is being evaluated in a study in healthy subjects (UP0018) with escalation of single 
intravenous (iv) and sc dosing. The outcomes are safety, tolerability, PK, and the PD effect on 
total IgG levels. Doses of UCB7665 1, 4, and 7mg/kg have been administered in 3 cohorts for 
the iv route and in 3 cohorts for the sc route. Preliminary information from the study is 
summarized below.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 20 of 353
In the iv cohorts, the maximum tolerated dose was reached at UCB7665 4mg/kg. The most 
common TEAEs in all iv cohorts were mild to moderate gastrointestinal disturbances (nausea, 
vomiting, and diarrhea) and mild to severe headaches. 
In the sc cohorts, a comparable tolerability profile was seen with UCB7665 7mg/kg sc and
4mg/kg iv. Adverse events of mild to moderate severity for headaches and gastrointestinal 
disturbances were observed. There were fewer cases of headache and gastrointestinal
disturbances in the overall sc cohorts compared to overall iv cohorts.
In 4-week and 13-week toxicity studies with 8-week, treatment-free recovery periods in 
Cynomolgus monkeys, UCB7665 induced the expected large decreases (75% to 90%) in plasma 
IgG in all animals which was maintained for the duration of both studies in the majority of the 
animals, with only minor effects on albumin levels. UCB7665 was well tolerated at the highest 
dose levels tested of UCB7665 150mg/kg sc and UCB7665 150mg/kg iv administered every
3 days (there was no observed adverse effect level [NOAEL]).
Further information on the PK, PD, and safety profiles for UCB7665 from nonclinical studies, 
and preliminary safety information from clinical studies (including data from this study), can be 
obtained from the current version of the UCB7665 Investigator’s Brochure.
Subjects will also have the option of providing additional informed consent for exploratory
DNA and RNA (mRNA and miRNA) analyses as described in Section 5.1.1.
3
STUDY OBJECTIVE(S)
3.1
Primary objective
The primary objective of the study is:

To evaluate the safety and tolerability of UCB7665 administered by sc infusion in subjects
with ITP
3.2
Secondary objectives
The secondary objectives of this study are:

To assess the clinical efficacy of UCB7665 as measured by the change in platelet count

To assess the PD effect of UCB7665 as measured by the change in total IgG concentration in 
serum
3.3
Exploratory objectives
The exploratory objectives of this study are:


To evaluate the clinical efficacy as measured by the change in ITP bleeding score

To evaluate the effect of UCB7665 on the concentrations of total protein, albumin, 
α-globulin and β-globulin, IgG subclasses, IgM, IgA, and IgE, and serum and plasma 
complement levels

To evaluate the emergence of ADA with respect to immunogenicity and PK/PD
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UCB
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 21 of 353

To evaluate the relationship between changes in platelet count and total IgG, IgG subclasses, 
ITP-specific autoantibodies

To assess the plasma concentrations of UCB7665 administered by sc infusion

To evaluate the genomic components of ITP to understand the molecular etiology, 
progression, and treatment of the disease, applicable only for subjects consenting to 
participate in the optional genomic analyses substudy. 

4
STUDY VARIABLES
4.1
Primary variable
The primary safety variable is:

Occurrence of TEAEs
4.2
Others and exploratory variables
4.2.1
Safety variables
The other safety variables are:

Vital sign values and change from Baseline over time (systolic and diastolic blood pressure, 
temperature, pulse rate, respiratory rate, and body weight)

12-Lead ECG parameters and change from Baseline over time

Laboratory values and change from Baseline over time (hematology including coagulation 
parameters, clinical chemistry, and urinalysis)

Values and change from Baseline in concentrations of total protein, albumin, α-globulin, and 
β-globulin over time

Change from Baseline in exploratory safety biomarkers over time

TEAEs leading to withdrawal of IMP
4.2.2
Efficacy variables
The efficacy variables are:

Response during the study: platelet count ≥30x109/L and at least 2-fold increase of the 
Baseline count

Complete Response during the study: platelet count ≥100x109/L

Platelet count ≥50x109/L during the study

Response by visit

Complete Response by visit

Platelet count ≥50x109/L by visit
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UCB
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Clinical Study Protocol
UCB7665
TP0001
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Page 22 of 353

The maximum value and maximum increase from Baseline in platelet count during the study

Value and change from Baseline in platelet count over time

Baseline-corrected AUEC for platelet count

Time to Response: time from starting treatment to achievement of Response

Time to Complete Response: time from starting treatment to achievement of Complete 
Response

Time to achieving platelet count ≥50x109/L

Duration of Response: measured from achievement of Response to loss of Response (loss of 
Response defined as platelet count below 30x109/L or less than 2-fold increase of Baseline 
platelet count)

Duration of Complete Response: measured from achievement of Complete Response to loss 
of Complete Response (loss of Complete Response defined as platelet count below 
100x109/L)

Duration of platelet count ≥50x109/L: measured from achievement of platelet count 
≥50x109/L to reduction of platelet count below 50x109/L

Clinical Response: platelet count ≥30x109/L and at least 2-fold increase from Baseline value 
and absence of bleeding

Time to Clinical Response: time from starting treatment to achievement of Clinical Response

Duration of Clinical Response: measured from achievement of Clinical Response to loss of 
Clinical Response (loss of Clinical Response defined as platelet count <30x109/L or less than 
2-fold increase from Baseline platelet count or presence of bleeding)

Complete Clinical Response: platelet count ≥100x109/L and absence of bleeding

Time to Complete Clinical Response: time from starting treatment to achievement of 
Complete Clinical Response

Duration of Complete Clinical Response: measured from achievement of Complete Clinical 
Response to loss of Complete Clinical Response (loss of Complete Clinical Response defined 
as platelet count <100x109/L or presence of bleeding)

No Clinical Response: platelet count <30x109/L or less than 2-fold increase from Baseline or 
presence of bleeding

ITP bleeding score over time

Value and change from Baseline in NFI-MS summary score over time
4.2.3
Pharmacokinetic variable
The PK variable is:

Plasma concentration of UCB7665 over time
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UCB
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 23 of 353
4.2.4
Pharmacodynamic variables
The PD variables are:

Minimum value and maximum decrease from Baseline in total IgG concentration during the 
study

Value and change from Baseline in total IgG concentrations over time

Change from Baseline in ITP-specific autoantibody in serum over time:

Change from Baseline in IgG subclass concentrations over time
4.2.5
Other immunological variables
Other immunological variables are:

Change from Baseline in serum immunoglobulin concentrations (total IgA, IgE, and IgM) 
over time

Change from Baseline in serum (C3 and C4) and plasma (C3a and C5a) complement levels 
over time

Change from Baseline in exploratory biomarkers relating to mechanism of action, disease 
activity, treatment response, and clinical outcome

ADA (anti-UCB7665 antibodies) status (negative/positive) and change from Baseline in
relative mass units over time

Change from Baseline in cytokines over time (for subjects experiencing infusion reactions)

Change from Baseline in serum BAFF levels over time

Lymphocyte counts (B and T)
5
STUDY DESIGN
5.1
Study description
This is a Phase 2, multicenter, open-label, multiple-dose, multiple-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 in subjects with primary persistent or chronic ITP.
Dose Arm 1 (15 subjects): UCB7665 4mg/kg sc (5 doses at an interval of 1 week)
Dose Arm 2 (15 subjects): UCB7665 7mg/kg sc (3 doses at an interval of 1 week)
Dose Arm 3 (6 to 12 subjects): UCB7665 10mg/kg sc (2 doses at an interval of 1 week)
Dose Arm 4 (6 to 12 subjects): UCB7665 15mg/kg sc (1 dose)
Dose Arm 5 (6 to 12 subjects): UCB7665 20mg/kg sc (1 dose)
The maximum duration of the study per subject is approximately 16 weeks, consisting of a 
Screening Period (1 to 28 days), a Dosing Period of 1 to 4 weeks, and an Observation Period of 
8 weeks.
Screening Period: The purpose of the Screening Period is to evaluate and confirm the subject’s 
eligibility. During the Screening Visit (Visit 1), subjects will sign a written Informed Consent 
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UCB
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 24 of 353
form prior to the conduct of any study-related procedures. The use of concomitant medication 
while in the study will be discussed, and the subject’s eligibility will be determined on the basis 
of the inclusion/exclusion criteria. The Screening Period should not exceed 28 days.
Dosing Period: The first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in 
the Dose Arm 1 will not be randomized. While recruitment is still ongoing, safety data for the
first 3 subjects up to 7 days after the last dose of the third subject in Dose Arm 1 will be 
reviewed by the DMC. During a second DMC meeting, all available safety data up to cut off date 
defined as 7 days after the last dose of the sixth subject in Dose Arm 1 will be reviewed. During 
these reviews recruitment in the dose arm will not be stopped. Following this review, the DMC 
will make a decision on whether to open Dose Arm 2 for enrollment. Once DMC has advocated 
the initiation of Dose Arm 2, the subsequent subjects will be randomly assigned in 1:1 ratio to 
either Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in the Dose 
Arm 1, the remaining subjects will be enrolled in Dose Arm 2.
After the safety data review of at least 6 subjects in Dose Arm 2 is done, the DMC will make a 
recommendation on whether to open Dose Arm 3 for enrollment. Once the DMC has advocated 
the initiation of Dose Arm 3 and the enrollment of 15 subjects in Dose Arm 2 has been 
completed, the subsequent subjects will be assigned to Dose Arm 3 only. After every third 
subject has been enrolled, the DMC will review all available safety data up to cut off date 
defined as 7 days after the dosing. Depending on the emerging safety data of 6 subjects in Dose 
Arm 3, the DMC will recommend whether to open Dose Arm 4 for enrollment or to include 
additional subjects in Dose Arm 3. If applicable, this step is planned to be done stepwise in 
groups of 3 subjects. A maximum, 12 subjects will be enrolled in Dose Arm 3. The DMC will 
recommend to open Dose Arm 4 for enrollment in a subsequent DMC meeting, if applicable.
Once the DMC has advocated the initiation of Dose Arm 4, the enrollment of Dose Arm 3 will 
be closed and all subsequent subjects will be assigned to Dose Arm 4. After every third subject is 
enrolled, the DMC will review all available safety data up to the cutoff date defined as 7 days 
after the dosing. Depending on the emerging safety data of 6 subjects in Dose Arm 4, the DMC 
will recommend to include additional subjects in Dose Arm 4 or not. If applicable, this step is 
planned to be done stepwise in groups of 3 subjects. A maximum of 12 subjects may be enrolled 
in Dose Arm 4. The DMC will recommend to open Dose Arm 5 for enrollment in a subsequent 
meeting, if applicable.
Once the DMC has advocated the initiation of Dose Arm 5, the enrollment of Dose Arm 4 will 
be closed and all subsequent subjects will be assigned to Dose Arm 5. After every third subject is 
enrolled, the DMC will review all available safety data up to the cutoff date defined as 7 days 
after the dosing. Depending on the emerging safety data of 6 subjects in Dose Arm 5, the DMC 
will recommend to include additional subjects in Dose Arm 5. If applicable, this step is planned 
to be done stepwise in groups of 3 subjects. A maximum of 12 subjects may be enrolled in Dose 
Arm 5.
At least 11 interim analyses will be performed. Based on the interim analyses, the DMC will 
assess the safety of UCB7665, determine whether to initiate subsequent dose arms and may
decide to adapt the dose regimen. Planned dosing may be discontinued for all subjects in a dose 
arm (see Section 6.5). Refer to Section 14.7 for details. 
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Clinical Study Protocol
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TP0001
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In case the DMC recommends reducing the number of doses (infusions) for any of the
predefined dose arms (as applicable) based on review of safety data, then the additional dose 
arms receiving a reduced number of doses will be considered as additional new dose arms for the 
study.
Observation Period: Following the last dose (or only dose administration for Dose Arms 4 and 
5), a visit will be scheduled 3 days postdose and weekly thereafter for 8 weeks to collect safety
and efficacy data.
5.1.1
Exploratory genomic analyses
During this study, subjects will also have the option of providing additional informed consent for 
exploratory DNA and RNA analyses. Participation in this additional portion of the study is 
optional and does not preclude subject’s eligibility for participation in the main study. The 
additional genomic samples must not be collected if the subject has not consented to participate 
in this exploratory genomic substudy.
Once subject provides consent, through a separate informed consent form, blood samples will be 
drawn as follows:
For DNA: Blood samples will be collected at Baseline (Visit 2) for all dose arms. Subsequent 
blood sample will be collected prior to the last dose (ie, Visit 7 for Dose Arm 1, Visit 5 for Dose 
Arm 2, and Visit 4 for Dose Arm 3).
For RNA: Blood samples will be collected at the following time points for different dose arms: 

Dose Arm 1: Baseline (Visit 2), 3 days after dose 1 (Visit 3), prior to the last dose (Visit 7),
and End of Study Visit (Visit 15).

Dose Arm 2: Baseline (Visit 2), 3 days after dose 1 (Visit 3), prior to the last dose (Visit 5), 
and End of Study Visit (Visit 13).

Dose Arm 3: Baseline (Visit 2), 3 days after dose 1 (Visit 3), prior to the last dose (Visit 4), 
and End of Study Visit (Visit 12).

Dose Arm 4: Baseline (Visit 2), 3 days after dosing (Visit 3) and End of Study Visit
(Visit 10).

Dose Arm 5: Baseline (Visit 2), 3 days after dosing (Visit 3) and End of Study Visit 
(Visit 10). 
For each DNA blood sample a volume of 6mL whole blood is needed and for each RNA sample 
a volume of 2.5mL whole blood is needed.
Failure to provide consent to participate in this substudy will not impact subject’s eligibility to 
participate in the main study.
Any exploratory biomarker or genomic analysis will only ever be related to the exploration of 
the underlying causes of ITP in patients, related biology, and drug response. Justification for 
additional genomic analyses is detailed in Section 5.4.6.
Details on the collection, storage, preparation, and shipping of samples will be presented in the 
Laboratory Manual provided separately.
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 26 of 353
Any results from this analysis will be reported separately and will not form a part of the main 
clinical study report.
5.1.2
Study duration per subject
The maximum duration of the study per subject is approximately 16 weeks.
Screening Period: 1 to 28 days (4 weeks)
Dosing Period: up to 4 weeks
Observation Period: 8 weeks
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.3
Planned number of subjects and sites
A total of up to approximately 48 to 66 subjects are planned to enter the Dosing Periods in the 
study (15 subjects in each of Dose Arms 1 and 2, and 6 to 12 subjects in Dose Arms 3, 4, and 5). 
To achieve the required number of eligible subjects to enter the Dosing Period, it is anticipated 
that approximately 90 subjects will need to be screened. These subjects will be enrolled at 
approximately 45 sites. First subject first visit is planned for Q1 2016, last subject last visit for 
Q2 2018.
5.1.4
Anticipated regions and countries
It is planned to recruit subjects in Europe and Australia for the study.
5.2
Schedule of study assessments
Table 5‒1 presents the tabular scheme of study assessments for the weekly UCB7665 4mg/kg 
dose arm (Dose Arm 1), Table 5‒2 presents the tabular scheme of study assessments for the 
weekly UCB7665 7mg/kg dose arm (Dose Arm 2), Table 5-3 presents the tabular scheme of 
study assessments for the weekly UCB7665 10mg/kg dose arm (Dose Arm 3), Table 5-4 presents 
the tabular scheme of study assessments for the one dose of UCB7665 15mg/kg, Table 5-5
presents the tabular scheme of study assessments for the one dose of UCB7665 20mg/kg and
Table 5‒6 presents the assessments to be performed on dosing days.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 27 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consent f
X
Demographic data
X
Verification of 
inclusion/exclusion 
criteria
X
X
Platelets for inclusion/
withdrawal check (local 
laboratory)g
X
X
X
X
X
Randomizationh
X
Withdrawal criteriai
X
X
X
X
X
X
General 
medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 28 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationj
X
X
X
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
X
X
X 
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xl
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis 
C
X
IGRA TB testm
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 29 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
TB signs and symptoms 
questionnaire
X
X
Blood sample for 
cytokines
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Whole blood sample for 
DNA (optional)
X
X
Whole blood sample for 
RNA (optional)
X
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
X
X
Call to IXRS for treatment 
kit number
X
X
X
X
X
Administration of IMP
X
X
X
X
X
Blood sampling for 
plasma concentration of 
UCB7665
X
X
X
X
X
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 30 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serum complements (C3
and C4) and plasma 
complements (C3a and 
C5a)
X
X
X
X
Blood collection for 
exploratory safety 
biomarkers 
X
Xo
X
X
X
X
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Serum BAFF levels
X
X
X
X
X
X
X
Blood collection for 
exploratory biomarker 
analysis
X
X
X
X
X
X
X
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
IgA, IgM, IgEp
X
X
X
X
ITP-specific 
autoantibodies q
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 31 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Headache questionnairer
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviews
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring; 
DNA=deoxyribonucleic acid; Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response 
system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
TB=tuberculosis.
a   Frequency of assessments on dosing days is detailed in Table 5‒6.  
b Visits 10, 12, and 14 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date.
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h The first 6 subjects will be enrolled in the Dose Arm 1 group only. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the 
DMC. Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, the subsequent subjects will be 
randomly assigned in 1:1 ratio to either Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in Dose Arm 1 and safety data review of at 
least 6 subjects in Dose Arm 2 is done, the subsequently enrolled subjects will be enrolled in Dose Arm 2 until a planned number of 15 subjects are enrolled.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4 .
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 32 of 353
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m The IGRA test will be performed in a central laboratory. Any IGRA-positive subjects will be withdrawn from the study.
n Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
o Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see 
Section 12.4).
p In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 7 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
q
r This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
s A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only. 
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ase of ea
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 33 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
X
Platelets for inclusion/withdrawal 
check (local laboratory)g
X
X
X
Randomizationh
X
Withdrawal criteriai
X
X
X
X
General medical/procedures history
X
ITP history
X
Prior and concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 34 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Physical examinationj
X
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters (hematology, 
chemistry, urinalysis)
Xl
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, hepatitis B, and 
hepatitis C
X
IGRA TB testm
X
TB signs and symptoms questionnaire
X
X
Blood sample for cytokines
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Whole blood sample for DNA 
(optional)
X
X
Whole blood sample for RNA 
(optional)
X
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
Call to IXRS for treatment kit number
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 35 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Administration of IMP
X
X
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
X
X
X
Serum complements (C3 and C4) and 
plasma complements (C3a and C5a)
X
X
X
X
Blood collection for exploratory safety
biomarkers
X
Xo
X
X
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Serum BAFF levels
X
X
X
X
X
Blood collection for exploratory 
biomarker analysis
X
X
X
X
X
Immunoglobulins (total IgG, IgG 
subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEp
X
X
X
X
ITP-specific autoantibodiesq
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
REDACTED COPY
X
OPY
X
Y 
X
D CO
X
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X
ACT
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 36 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Headache questionnairer
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviews
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IGRA= interferon-gamma release assay; IMP=investigational medicinal product; ITP=immune thrombocytopenia; 
IXRS= interactive voice/web response system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue 
Index for multiple sclerosis; TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.
b Visits 8, 10, and 12 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the last dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose.
e The visit windows in the Observation Period are relative to the final dosing visit date. 
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h The first 6 subjects will be enrolled in the Dose Arm 1 group. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the DMC. 
Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, the subsequent subjects will be randomly 
assigned in 1:1 ratio to either Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in Dose Arm 1 and safety data review of at least 
6 subjects in Dose Arm 2 is done, the subsequently enrolled subjects will be enrolled in Dose Arm 2 until a planned number of 15 subjects are enrolled.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 37 of 353
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m The IGRA test will be performed in a central laboratory. Any IGRA-positive subjects will be withdrawn from the study.
n Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
o Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see 
Section 12.4).
p In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 5 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
q
r This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
s A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
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case of 
tion 
case of 


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 38 of 353
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Visit 
1
2a
3
4a
5
6
7b
8
9b
10
11b
12
BL 
Visit
EOS/EW
c
Telephone 
Contact
1
2d
3
4d
Day
-28 to -1
1
2
3
4
8
9
10
11
15
22
29
36
43
50
64
Week
1
1
1
1
2
2
2
2
3
4
5
6
7
8
10
Visit 
Window
±1d
±2de
±1d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d f
Written informed consentg
X
Demographic data
X
Verification of 
inclusion/exclusion criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory) h
X
X
Withdrawal criteriai
X
X
X
General medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
REDACTED COPY 
OP
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AC
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 39 of 353
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Visit 
1
2a
3
4a
5
6
7b
8
9b
10
11b
12
BL 
Visit
EOS/EW
c
Telephone 
Contact
1
2d
3
4d
Day
-28 to -1
1
2
3
4
8
9
10
11
15
22
29
36
43
50
64
Week
1
1
1
1
2
2
2
2
3
4
5
6
7
8
10
Visit 
Window
±1d
±2de
±1d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d f
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationj
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xl
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis C
X
IGRA TB testm
X
TB signs and symptoms 
questionnaire
X
X
Blood sample for cytokines
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 40 of 353
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Visit 
1
2a
3
4a
5
6
7b
8
9b
10
11b
12
BL 
Visit
EOS/EW
c
Telephone 
Contact
1
2d
3
4d
Day
-28 to -1
1
2
3
4
8
9
10
11
15
22
29
36
43
50
64
Week
1
1
1
1
2
2
2
2
3
4
5
6
7
8
10
Visit 
Window
±1d
±2de
±1d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d f
Whole blood sample for 
DNA (optional)
X
X
Whole blood sample for 
RNA (optional)
X
X
X
X
Serum pregnancy test
X
  
Urine pregnancy test
X
X
X
Call to IXRS for treatment 
kit number
X
X
Administration of IMP
X
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
X
X
Serum complements (C3 
and C4) and plasma 
complements (C3a and C5a)
X
X
X
REDACTED COPY 
OP
X
D
X
CO
C
O
X
ACT
X
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RE AC
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eting authorization application and any extensions or variations thereof.
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This document cannot be used
no
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 41 of 353
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Visit 
1
2a
3
4a
5
6
7b
8
9b
10
11b
12
BL 
Visit
EOS/EW
c
Telephone 
Contact
1
2d
3
4d
Day
-28 to -1
1
2
3
4
8
9
10
11
15
22
29
36
43
50
64
Week
1
1
1
1
2
2
2
2
3
4
5
6
7
8
10
Visit 
Window
±1d
±2de
±1d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d f
Blood collection for 
exploratory safety
biomarkers
X
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Serum BAFF levels
X
X
X
X
Blood collection for 
exploratory biomarker 
analysis
X
X
X
X
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEp
X
X
X
X
ITP-specific autoantibodiesq
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairer
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviews
X
REDACTED COPY 
OP
X
D
Xo
D C
o
CO
AC
O
AC
AC
AC
RE AC
RE
RE
RE
any marketing authorization application and any extensions or variations thereof.
15 
here
15 Fe
e
Fe
on
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tion Pe
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tion Pe
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ot
an


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 42 of 353
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IGRA= interferon-gamma release assay; IMP=investigational medicinal product; ITP=immune 
thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; 
NFI-MS=Neurological Fatigue Index for multiple sclerosis; TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.
b Visits 7, 9, and 11 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the last dose.
d If the TC is on the same day as an on-site visit, the TC may be skipped.
e A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose.
f The visit windows in the Observation Period are relative to the final dosing visit date. 
g Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
h Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4. 
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m The IGRA test will be performed in a central laboratory. Any IGRA-positive subjects will be withdrawn from the study.
n Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
o Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see
Section 12.4).
p In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 6 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
q
r This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
s A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 43 of 353
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose Arm 4)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of 
inclusion/exclusion criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)g
X
Withdrawal criteriah
X
General medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 44 of 353
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose Arm 4)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
12-lead ECGj
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xk
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis C
X
IGRA TB testl
X
TB signs and symptoms 
questionnaire
X
X
Blood sample for cytokines
X
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Whole blood sample for DNA 
(optional)
X
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This document cannot be used to 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 45 of 353
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose Arm 4)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Whole blood sample for RNA 
(optional)
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
Call to IXRS for treatment kit 
number
X
Administration of IMP
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
Serum complements (C3 and 
C4) and plasma complements 
(C3a and C5a)
X
X
X
Blood collection for 
exploratory safety biomarkers
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
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X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 46 of 353
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose Arm 4)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Blood collection for 
exploratory biomarker 
analysis
X
X
X
Immunoglobulins (total IgG, 
IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgE
X
X
X
ITP-specific autoantibodieso
X
X
X
ITP bleeding scale
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairep
X
X
X
X
X
X
X
X
X
Subject exit interviewq
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IGRA= interferon-gamma release assay; IMP=investigational medicinal product; ITP=immune 
thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; 
NFI-MS=Neurological Fatigue Index for multiple sclerosis; TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.
b Visits 5, 7, and 9 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the dose.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 47 of 353
d If the TC is on the same day as an on-site visit, the TC may be skipped.
e The visit windows in the Observation Period are relative to the dosing visit date. 
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 1, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
i A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
j The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
k At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
l IGRA test will be performed in a central laboratory. It is recommended that the QFT-GIT be the first test performed at Screening to reduce the number of 
screening procedures conducted for any IGRA-positive subjects that may need to be withdrawn from the study.
m Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
n Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see 
Section 12.4).
o
p This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
q A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
PY 
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This document cannot be used to support any marketing
be recor
ting 
be recor


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 48 of 353
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose Arm 5)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of 
inclusion/exclusion criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)g
X
Withdrawal criteriah
X
General medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
REDACTED COPY 
PY
OP
C
TE
TE
TE
TE
E
TE
ED
RE
port any marketing authorization application and any extensions or variations thereof.
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nn
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nt
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 49 of 353
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose Arm 5)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
12-lead ECGj
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xk
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis C
X
IGRA TB testl
X
TB signs and symptoms 
questionnaire
X
X
Blood sample for cytokines
X
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Whole blood sample for DNA 
(optional)
X
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th
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o
us
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cann


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 50 of 353
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose Arm 5)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Whole blood sample for RNA 
(optional)
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
Call to IXRS for treatment kit 
number
X
Administration of IMP
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
Serum complements (C3 and 
C4) and plasma complements 
(C3a and C5a)
X
X
X
Blood collection for 
exploratory safety biomarkers
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Serum BAFF levels
X
X
X
REDACTED COPY 
P
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C
X
PY
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RE
marketing authorization application and any extensions or variations thereof.
15 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 51 of 353
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose Arm 5)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Blood collection for 
exploratory biomarker 
analysis
X
X
X
Immunoglobulins (total IgG, 
IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgE
X
X
X
ITP-specific autoantibodieso
X
X
X
ITP bleeding scale
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairep
X
X
X
X
X
X
X
X
X
Subject exit interviewq
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IGRA= interferon-gamma release assay; IMP=investigational medicinal product; ITP=immune 
thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; 
NFI-MS=Neurological Fatigue Index for multiple sclerosis; TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.
b Visits 5, 7, and 9 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the dose.
REDACTED COPY 
PY
TE
OP
CTE
TE
TE
E
T
RE
RE
RED
RE
y marketing authorization application and any extensions or variations thereof.
15 
here
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oglobul
use
oglobul
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e Index f
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n dosing
nno
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This document
it is 8 w
nt c
it is 8 w


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 52 of 353
d If the TC is on the same day as an on-site visit, the TC may be skipped.
e The visit windows in the Observation Period are relative to the dosing visit date. 
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 1, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
i A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
j The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
k At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
l The IGRA test will be performed in a central laboratory. Any IGRA-positive subjects will be withdrawn from the study.
m Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
n Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see
Section 12.4). 
o
p This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
q A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 53 of 353
Table 5‒6:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of 
infusion
4h after end of 
infusion
6h after end of 
infusiona
Withdrawal criteria
X
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X
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X
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X
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X
X
X
X
X
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X
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X
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X
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X
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X
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X
ITP-specific autoantibodiese
X
Blood sampling for UCB7665 plasma 
concentration
X
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X
Serum (C3 and C4) and plasma 
complements (C3a and C5a)f
X
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biomarkersg
X
X
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 54 of 353
Table 5‒6:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of 
infusion
4h after end of 
infusion
6h after end of 
infusiona
Blood collection for exploratory 
biomarker analysis
X
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Xh
Xi
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(optional)j
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X
X
X
X
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X
AE=adverse event; BAFF=B cell activating factor; DNA=deoxyribonucleic acid; ECG=electrocardiogram; h=hours; Ig=immunoglobulin; IMP=investigational 
medicinal product; ITP=immune thrombocytopenia; NFI-MS=Neurological Fatigue Index for multiple sclerosis; PRO=Patient Reported Outcomes; 
RNA=ribonucleic acid; 
a For Dose Arms 3, 4 and 5 only
b In addition to time points mentioned, vital signs will be evaluated every 15 minutes during infusion. Respiratory rate will be assessed only once predose.
c The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
d Total IgG and IgG subclasses. 
e Evaluation of ITP-specific autoantibodies will be performed prior to dose 1 only. 
f Serum and plasma complements (C3a and C5a) will be assessed prior to dose 1 and dose 3 only.
g
h Blood sample for Baseline cytokine values will be obtained and analyzed at Baseline (Visit 2) pre-dose for all subjects. Also for all subjects on Dose Arm 3, the 
blood sample for cytokine values will be obtained and analyzed at Visit 4 pre-dose.
i Additional cytokine blood sample to be taken at 4h after end of infusion only in subjects with infusion reaction.
j For DNA, samples are taken at Baseline (Visit 2) and last dose only. For RNA, samples are taken at Baseline (Visit 2), Visit 3, at last dose, and End of Study 
Visit. All samples collected prior to dosing (if applicable for visit).
k PRO endpoint (NFI-MS) will be assessed prior to dose 1 only.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 55 of 353
5.3
Schematic diagram
Figure 5‒1 presents a schematic diagram for the study design.
Figure 5‒1: Schematic diagram
DMC=Data Monitoring Committee; EOS=End of Study
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 56 of 353
5.4
Rationale for study design and selection of dose
5.4.1
Pathophysiology of ITP
Production of pathogenic autoantibodies is a major feature of a number of autoimmune diseases 
often associated with a specific pathomechanism. Autoantibodies against platelet antigens are 
considered to be a hallmark of ITP. Production of pathogenic IgG autoantibodies by plasma cells 
is accepted as the central underlying pathophysiological mechanism in a number of 
IgG-mediated autoimmune diseases, which includes ITP. In some patients, antibodies recognize 
antigens derived from a single glycoprotein; whereas in others, antibodies recognize multiple 
glycoproteins. The spleen is the key organ in the pathophysiology of ITP, not only because 
platelet autoantibodies are formed in the white pulp, but also because mononuclear macrophages 
in the red pulp destroy immunoglobulin-coated platelets.
Treatments aimed at reducing the quantity of circulating IgG autoantibodies are being used for 
primary and secondary therapy of autoimmune diseases, particularly where corticosteroid-based 
immune suppression is not or no longer effective. The therapeutic approach of these treatments is 
based on lowering levels of pathogenic autoantibodies, which represents rational and effective 
treatment modalities of autoimmune diseases.
5.4.2
Mechanism of action of UCB7665
UCB7665 is a humanized IgG4 monoclonal antibody that is being developed as an inhibitor of 
the activity of FcRn. The FcRn receptor recycles IgG and albumin and transports it 
bidirectionally across epithelial barriers. Recent studies have shown that FcRn rescues both IgG 
and albumin from intracellular lysosomal degradation by recycling it from the sorting endosome 
to the cell surface (Anderson et al, 2006). UCB7665 has been specifically designed to block IgG 
binding to FcRn without blocking the binding and recycling of albumin.
By blocking the activity of FcRn, UCB7665 accelerates the catabolism of IgG antibodies, 
including IgG autoantibodies. The aim is to reduce the concentration of pathogenic IgG in 
patients with autoimmune diseases mediated by the action of IgG autoantibodies.
5.4.3
Choice of study design and endpoints
The primary objective of the study is evaluation of safety and tolerability of UCB7665 
administered as an sc infusion in subjects with ITP. The study utilizes a sequential adaptive 
design with at least 11 interim analyses as described in Section 14.7. This design was chosen to 
permit adequate monitoring of the safety of the subjects in the study.
The study will evaluate the platelet count as a surrogate marker for clinical efficacy in ITP in 
accordance with the European Medicines Agency (EMA) guidance for clinical development of 
medicinal products for chronic ITP (EMA/CHMP/153191/2013, 2014). The platelet count 
measures treatment activity and is believed to be a reliable predictor of clinical benefit. 
Endpoints related to Response and Complete Response as defined in the guidance will be 
evaluated. In addition, a platelet response of >50x109/L will be evaluated in the study.
5.4.4
Safety of UCB7665
Safety and tolerability of UCB7665 7mg/kg sc dose has been evaluated in healthy subjects. The 
most common TEAEs were mild to moderate gastrointestinal disturbances (nausea, vomiting, 
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
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Page 57 of 353
and diarrhea) and headaches ranging from mild to moderate intensity. Details of AEs seen with 
UCB7665 7mg/kg administered by the iv route are presented in Section 5.4.5.
5.4.5
Rationale for dose selection
A single ascending dose study in healthy subjects (UP0018) explored the dose range of 
UCB7665 (between 1 and 7mg/kg) and characterized the PK and PD effect on total IgG. 
Preliminary data indicate that mean absolute decreases in IgG and mean percent change from 
Baseline IgG were greater in the active dose groups (n=6 each) compared to the pooled iv and sc 
placebo group (n=12) with maximum decreases of 49.3% (range: 44.6% to 55.9%) observed on 
Day 6 for a UCB7665 7mg/kg iv dose and 42.8% (range: 39.6% to 48.6%) on Day 9 for a 
UCB7665 7mg/kg sc dose.
The dose-exposure-response relationship, with total IgG as primary endpoint, was determined 
using non-linear mixed effects modeling. The derived population PK-PD (structural PK-PD 
model based on that of Lowe [Lowe et al, 2010]) was then used to guide, through simulation, the 
selection of appropriate repeat dose regimens that would mimic decreases achieved by 
plasmapheresis paradigms and result in IgG reductions of 70% or greater. 
The model-based simulations demonstrate that weekly doses of UCB7665 4mg/kg for 
5 consecutive weeks are expected to produce maximum mean IgG reductions of >70%. Similar 
reductions are predicted to be achieved following 3 consecutive weekly doses of
UCB7665 7mg/kg.
Following iv administration in UP0018, the maximum tolerated dose was identified as 
UCB7665 4mg/kg due to AEs seen at the higher dose of 7mg/kg with severe headache and 
moderate diarrhea being reported. The tolerability profile of UCB7665 7mg/kg given as an sc 
infusion was more favorable than the equivalent iv dose and similar to the UCB7665 4mg/kg iv 
dose with mild to moderate cases of gastrointestinal disturbances and headaches being reported 
at a lower incidence.
Therefore, doses of UCB7665 4mg/kg given once weekly for 5 weeks(Dose Arm 1) and 
UCB7665 7mg/kg given once weekly for 3 weeks (Dose Arm 2) have been selected as the initial 
doses to evaluate the safety, tolerability and effect on platelet count in subjects with primary 
persistent or chronic ITP. Both dose regimens have the same cumulative dose of approximately
UCB7665 20mg/kg.
Preliminary data from the current study indicates that the current dose regimens of UCB7665 
4mg/kg and UCB7665 7mg/kg have been well tolerated. Hence the additional dose regimens of 
UCB7665 10mg/kg given once weekly for 2 weeks (Dose Arm 3) and of UCB7665 20mg/kg 
given once only (Dose Arm 5) are planned to further investigate the safety, tolerability and effect 
on platelet count of the same cumulative dose of UCB7665 20mg/kg but administered in dose 
regimes with higher dosages given in less infusions. The dose of UCB7665 15mg/kg given once 
only (Dose Arm 4) has been selected in addition as a risk mitigation as it is bridging the dose of 
UCB7665 10mg/kg given once weekly for 2 weeks (Dose Arm 3) and the dose of UCB7665 
20mg/kg given once only (Dose Arm 5).
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 58 of 353
5.4.6
Justification for additional genomic analyses
DNA analysis
A genetic component in ITP has long been suspected to predispose some persons to develop ITP 
when exposed to a provocative event.
Further, the hypothesis of underlying genetic risk for ITP is supported by rare anecdotal and case 
reports of familial ITP. Affected members of these families present with ITP that meets the 
clinical criteria for primary ITP, but demonstrates a convincing pattern of inheritance. A 2006 
review of the Pediatric and Adult Registry of Chronic ITP (PARC-ITP) (Johnsen, 2012) found 
that 10 of 445 (2.2%) of pediatric patients reported a positive family history of ITP. However, 
identification of susceptibility genes in ITP, via family linkage studies or genome wide 
association studies, have not yet been forthcoming, likely due to the rarity of familial ITP 
families available for study and the heterogeneity of ITP sporadic cases. Identification and 
characterization of a genetic and/or epigenetic component of familial ITP will lead to important 
clues into the pathogenesis of more common forms of ITP and possibly advance understanding 
of drug response phenotypes. 
RNA analysis
Gene expression (mRNA) analyses have identified distinct gene transcription signatures from 
whole blood associated with many autoimmune diseases including rheumatoid arthritis, systemic 
lupus erythematosus, and ITP. Such signatures have provided molecular insight into disease 
biology and can facilitate patient stratification via gene expression panels predictive of 
therapeutic response and clinical outcomes. 
Collection of blood for RNA analysis will enable identification of candidate markers for 
treatment effect and safety, and determine the feasibility of patient stratification.
MicroRNA analysis
MicroRNA are short (19-25 nucleotides) evolutionarily conserved single-stranded RNA 
molecules that regulate the expression of genes involved in diverse biological processes. The 
effect of miRNA on mRNA is mediated through the binding of the miRNA to the target mRNA 
ribonucleoprotein complex resulting in altered expression and decreased protein translation.  
Regulated miRNA in ITP significantly affect both gene and protein expression in T cells, 
indicating that they may be important regulatory molecules involved in the loss of immune 
tolerance in ITP.
In summary, the genetic, epigenetic, and genomic elements of ITP are complex and require 
further elucidation to understand the cause, progression, and appropriate treatment of ITP. 
Through the voluntary collection of blood DNA/and RNA samples from consenting subjects, this 
substudy will help enable further investigation of this complex disease.
6
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 59 of 353
2. Subject is considered reliable and capable of adhering to the protocol, visit schedule, or 
medication intake according to the judgment of the investigator.
3. Subject is male or female, ≥18 years of age at Visit 1 (Screening).
4. Subject has a diagnosis of primary ITP for a minimum of 3 months prior to Screening Visit. 
5. Subject has a platelet count <30x109/L at Screening and <35x109/L at Baseline (Visit 2).
Measured as follows: At Screening Visit, 2 separate blood collections for platelet count to be 
performed on the same day with at least 1 value below 30x109/L and both values below 
35x109/L. At Baseline Visit (Visit 2), a platelet measure will be taken locally and the value 
should be below 35x109/L.
6. Subject has a current or history of a peripheral blood smear consistent with ITP 
(thrombocytopenia with normal size or only slightly enlarged platelets and normal red and 
white blood cell morphology).
7. Female subjects of childbearing potential must have a negative serum pregnancy test at the 
Screening Visit, which is confirmed to be negative by urine testing prior to the first dose of 
IMP at Week 1 (Visit 2) and prior to further dosing at each study visit thereafter. 
Female subjects of childbearing potential must agree to use a highly effective method of birth 
control, during the study and for a period of 2 months after their final dose of IMP. Highly 
effective forms of birth control are methods which achieve a failure rate of less than 1% per 
year when used consistently and correctly. Highly effective methods of birth control include:

Combined (estrogen- and progesterone-containing) hormonal contraception (oral, 
implant, injectable) associated with inhibition of ovulation (which must be stable for at 
least 1 full month prior to Screening [Visit 1], and should remain stable during the study).

Progesterone-only hormonal contraceptives (oral, implant, injectable) associated with 
inhibition of ovulation (which must be stable for at least 1 full month prior to Screening 
[Visit 1], and should remain stable during the study).

Progesterone-releasing intrauterine systems or the TCu 380A intrauterine device.

Vasectomized partner (provided sole partner and partner has medical proof of surgical 
success).

True heterosexual sexual abstinence is an acceptable form of contraception when this is 
in line with the preferred and usual lifestyle of the person. Periodic abstinence (eg, 
calendar, ovulation, symptothermal, postovulation methods), declaration of abstinence for 
the duration of the study, and withdrawal are not acceptable methods of contraception.
Women not agreeing to use birth control must be of nonchildbearing potential, defined as 
being:

Postmenopausal (for at least 2 years before the Screening Visit), verified by serum 
follicle-stimulating hormone level >40mIU/mL at the Screening Visit, or

Permanently sterilized (eg, bilateral tubal occlusion, hysterectomy, bilateral 
salpingectomy), or

Congenitally sterile
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 60 of 353
8. Contraception methods for male subjects and their female partners:

Male subject with a partner of childbearing potential must be willing to use a condom 
when sexually active during the study and for 3 months after the final administration of 
IMP.

In addition the female partner of childbearing potential of a male subject must be willing 
to use a highly effective method of contraception (as above), during the study period and 
for 3 months after the final administration of IMP.
9. Subject has adequate peripheral venous access.
10. Subject has responded to previous ITP therapy (according to the judgment of the 
investigator).
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria are met:
1. Subject has participated in another study of an IMP (or a medical device) within the previous 
30 days of Screening Visit or is currently participating in another study of an IMP (or a 
medical device).
2. Subject has a known hypersensitivity to any components of the IMP.
6.2.1
Exclusion criteria related to health status
3. Subject has a Karnofsky Performance Status (Appendix 18.1) rating <60% at Screening
Visit.
4. Subject has an IgG level ≤6g/L at Screening Visit.
5. Subject has a partial thromboplastin time (PTT) ≥1.5x upper limit of normal (ULN) or 
International Normalized Ratio (INR) ≥1.5 at Screening Visit.
6. Subject has any medical condition (acute or chronic illness) or psychiatric condition that, in 
the opinion of the investigator, could harm the subject or would compromise the subject’s 
ability to participate in this study.
7. Subject has 12-lead ECG with changes considered to be clinically significant upon medical 
review. 
8. Subject has a glycosylated hemoglobin (HbA1c) value >8% at Screening Visit.
9. Subject has renal impairment, defined as:

Serum creatinine level of ≥1.4mg/dL for females and ≥1.5mg/dL for males at 
Screening Visit. 
10. Subject has 2xULN of any of the following: alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), or alkaline phosphatase (ALP), or >ULN total bilirubin (≥1.5xULN 
total bilirubin if known Gilbert’s syndrome). If the subject has elevations only in total 
bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible
undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 61 of 353
For subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a Baseline 
diagnosis and/or the cause of any clinically meaningful elevation must be understood and 
recorded in the electronic Case Report form (eCRF).
If subject has >ULN for ALT, AST, or ALP that does not meet the exclusion limit at 
screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing 
clinically relevant increase. In case of a clinically relevant increase, inclusion of the subject 
must be discussed with the Medical Monitor. 
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes rescreening (see Section 6.3).
11. Female subject who is pregnant or lactating.
12. Subject has planned an elective surgical procedure in the coming 6 months.
6.2.2
Exclusion criteria related to medical history
13. Subject has a history of chronic alcohol or drug abuse within the previous 12 months of 
Screening Visit.
14. Subject has evidence of a secondary cause of immune thrombocytopenic purpura from the 
past medical history (eg, bacterial or viral infection, past medical history of leukemia, 
lymphoma, common variable immunodeficiency, systemic lupus erythematosus, 
auto-immune thyroid disease) or to drug treatments (eg, heparin, quinine, antimicrobials, 
anticonvulsants) or subject has a multiple immune cytopenia, eg, Evan’s syndrome.
15. Subject has a history of clinically relevant ongoing chronic infections including but not 
limited to human immunodeficiency virus (HIV), hepatitis B, hepatitis C, active or latent 
tuberculosis, or is tested positive for HIV, hepatitis B, or hepatitis C at the Screening Visit.
16. Subject has a family history of primary immunodeficiency.
17. Subject has a clinically relevant active infection (eg, sepsis, pneumonia, abscess) or has had a 
serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) 
within 6 weeks prior to the first dose of IMP.
18. Subject has active neoplastic disease or history of neoplastic disease within 5 years of 
Screening Visit (except for basal or squamous cell carcinoma of the skin or carcinoma in situ 
of the uterine cervix which has been definitively treated with standard of care approaches). 
19. Subject has a history of a major organ transplant or hematopoietic stem cell/marrow 
transplant.
20. Subject has a history of known inflammatory bowel disease, diverticular disease, or has a 
history of confirmed, duodenal, gastric or esophageal ulceration in the past 6 months.
21. Subject has experienced a clinically symptomatic gastrointestinal bleed (positive hemoccult 
tests without any signs and symptoms of gastrointestinal bleedings will not be considered as 
“clinically symptomatic”) in the last 6 months prior to Screening Visit and/or has current 
gastritis or esophagitis and/or has a known risk for clinically relevant gastrointestinal
bleeding beyond ITP.
22. Subject has experienced intracranial bleed in the last 6 months prior to Screening Visit.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 62 of 353
23. Subject has a medical history of thrombosis within the past 5 years or a history of thrombosis 
with unknown cause at any time or a significant known risk for thrombosis.
24. Subject has a history of coagulopathy disorders other than ITP.
25. Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or 
with latent TB (LTB) infection or current history of nontuberculous mycobacterial infection 
(NTMBI) are excluded.
a.
Known TB infection whether present or past is defined as:

Active TB infection or clinical signs and symptoms suggestive of TB (pulmonary or 
extrapulmonary).

History of active TB infection involving any organ system or findings in other organ systems 
consistent with TB infection.

Any historical evidence by radiography or other imaging modalities consistent with 
previously active TB infection.
b. High risk of acquiring TB infection is defined as:

Known exposure to another person with active TB infection within the 3 months prior to 
Screening.

Time spent in a healthcare delivery setting or institution where individuals infected with TB 
are housed and where the risk of transmission of infection is high.
c.
LTB infection (refer to Section 12.8.1 for further details and instructions).
d. NTMBI is defined as a group of lung infections caused by mycobacteria different from 
mycobacterium tuberculosis infections.
26. Subjects with known TB infection, at high risk of acquiring TB infection, or LTB infection, 
or current/history of NTMBI are excluded.
6.2.3
Exclusion criteria related to concomitant medications/procedures
27. Subject has received a live vaccination within 8 weeks prior to the Baseline Visit; or intends 
to have a live vaccination during the course of the study or within 7 weeks following the final 
dose of IMP. 
28. Subject has received any experimental biological agent within or outside of a clinical study in 
the past 3 months or within 5 half-lives prior to Baseline (whichever is longer).
29. Subject has had prior treatment with rituximab in the 6 months prior to the Baseline Visit or 
subject has had prior treatment with rituximab in the 12 months prior to Baseline and B cells 
are not within the normal range.
30. Subject has not completed the washout period for the immunosuppressants, biologics and 
other therapies as detailed in Table 6‒1. Medications as presented in Table 6‒1 are prohibited 
during the study.
Subject is currently receiving any of the prohibited medications listed in Section 7.8.2 or 
receiving immunosuppressant medications in doses higher than the maximum permissible 
dose for the study as per Section 7.8.1.
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 63 of 353
Table 6‒1:
Washout periods for immunosuppressants, biologics and other 
therapies
Generic name (most common commercial/trade 
names)
Washout period relative to Baseline Visit 
(regardless of route)
Immunosuppressants
Cyclophosphamide 
6 months
Pimecrolimus (Elidel®)
4 weeks
Vinca alkaloids (vincristine, vinblastine)
12 weeks
Biologics (mAbs and fusion proteins)
Abatacept (CTLA 4-Ig) (Orencia®)
6 months
Belimumab (Benlysta™)
6 months
Golimumab (Simponi™)
6 months
Natalizumab (Tysabri®)
6 months
Ofatumumab (Arzerra)
6 months
Rituximab (Rituxan®) and ocrelizumab
6 months
TACI-Ig (Atacicept)
10 months
Veltuzumab
6 months
Other biologics
3 months
Others
Intravenous immunoglobulin
4 weeks
IPP-201101 (Lupuzor™)
3 months
Plasma exchange (PLEX)
4 weeks
TPO-R agonists (eltrombopag, romiplostim)
4 weeks
Anti-D
4 weeks
Antiplatelets and Anticoagulants (Vitamin K 
antagonists)
Warfarin
2 weeks
Fenprocoumon
2 weeks
Acenocoumarol
2 weeks
Heparin
1 week
Clopidogrel
1 week
Salicylates (Aspirin)
1 week
Dipyramidole
1 week
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 64 of 353
Table 6‒1:
Washout periods for immunosuppressants, biologics and other 
therapies
Generic name (most common commercial/trade 
names)
Washout period relative to Baseline Visit 
(regardless of route)
Prasugrel
1 week
Ticagrelor
1 week
Tirofiban
1 week
Abciximab
1 week
31. Subject has undergone a splenectomy in the 3 months prior to the Baseline Visit or subject 
was splenectomized >3 months prior to Baseline but was not vaccinated following local 
recommendations. 
32. Subject has received IVIg in the 4 weeks prior to the Baseline Visit.
33. Subject has received TPO-R agonists in the 4 weeks prior to Baseline Visit.
34. Subject has received cyclophosphamide in the 6 months prior to the Baseline Visit.
35. Subject has received anti-D immunoglobulin in the 4 weeks prior to the Baseline Visit.
6.3
Rescreening
Subjects with isolated test results that are outside the specified ranges and that are deemed 
potentially as clinically non-significant can be enrolled without retesting at the discretion of the 
investigator, following discussion and agreement with the Medical Monitor/study physician, if 
appropriate. If a subject has 1 isolated test result outside the specific range which is deemed 
clinically significant, retesting may be allowed at the discretion of the investigator, following 
discussion and agreement with the Medical Monitor/study physician. If the normalization of the 
test result occurs within the Screening Period, then no other screening procedures need to be 
repeated.
6.4
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care.
Subjects should be withdrawn from the study if any of the following events occur:
1. Subject withdraws his/her consent.
2. Subject develops an illness or has a change in health status that would interfere with his/her 
continued participation, including but not limited to:

Subject has a serious infective episode requiring hospitalization or iv antibiotic therapy 
(including but not limited to bacteremia or sepsis, bacterial meningitis, osteomyelitis or 
septic arthritis, bacterial pneumonia, or visceral abscess).

Subject experiences a severe AE of gastrointestinal disturbance or headache which is
considered related to the IMP in the opinion of the investigator.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 65 of 353

Subject has a severe infusion reaction requiring corticosteroid and/or epinephrine 
therapy.

Subject has an anaphylactic reaction requiring corticosteroid and/or epinephrine therapy.

Subject has a life threatening bleeding event.

Subject has a TB test that is confirmed positive or any further evidence suggestive of
potential TB infection (eg, close exposure) and further examinations result in a diagnosis 
of active TB or LTB. Refer to Section 12.8.1 for further details and instructions.

If an NTMBI infection is identified during a study, the same withdrawal procedures as 
those used for an active TB infection identified during the study should be followed.
3. Subject requires rescue therapy (Section 7.8.3).
4. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
5. The sponsor or a regulatory agency requests withdrawal of the subject.
Subjects MAY be withdrawn from the study if any of the following events occur:
1. Subject is noncompliant with the study procedures or medications in the opinion of the 
investigator.
2. Subject takes prohibited concomitant medications as defined in this protocol that could 
compromise subject’s safety.
Subjects MUST stop treatment with the IMP if the platelet count is >350x109/L during the 
Dosing Period. Subjects should continue in the study and attend the protocol defined visits in the 
Observation Period.
6.4.1
Potential drug induced liver injury IMP discontinuation criteria
Subjects with PDILI must be assessed to determine if IMP must be discontinued. In addition, all 
concomitant medications and herbal supplements that are not medically necessary should also be 
discontinued.
The PDILI criteria below require immediate and permanent discontinuation of IMP:

Subjects with either of the following:

ALT or AST ≥5xULN

ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 
The PDILI criterion below requires immediate discontinuation of IMP:

Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).
If a nondrug-related cause for the symptoms can be confirmed, these subjects may resume IMP 
administration after discussion with responsible UCB physician, but only when the requirements 
for rechallenge with IMP as provided in Section 12.7.1.2.1 are followed.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 66 of 353
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
investigator.

Subjects with ALT or AST ≥3xULN (and ≥2x Baseline) and <5xULN, total bilirubin 
<2xULN, and no eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis (eg, 
fatigue, nausea, vomiting, right upper quadrant pain, or tenderness).
Evaluation of PDILI must be initiated as described in Section 12.7.1. If subjects are unable to 
comply with the applicable monitoring schedule, IMP must be discontinued immediately.

For all other withdrawal criteria, investigators should contact the Medical Monitor, whenever 
possible, to discuss the withdrawal of a subject in advance. Subjects who are withdrawn will 
not be replaced.
Subjects who decide to withdraw from the study will be encouraged to return to the clinic for all 
visits during the Observation Period and to complete the End-of-Study Visit (scheduled 8 weeks 
after final dose of IMP). If a subject is unwilling to complete the Observation Period, then 
subjects will be encouraged to complete at least 2 more study visits: Early Withdrawal Visit and 
End-of-Study Visit.
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow up, the investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), and document his/her effort 
(date and summary of the phone call and copy of the written message in the source documents), 
to complete the final evaluation. All results of these evaluations and observations, together with a 
narrative description of the reason(s) for removing the subject, must be recorded in the source 
documents. The eCRF must document the primary reason for withdrawal or discontinuation. In
case the subject is early terminated due to withdrawal of consent, the reason why the subject
withdrew consent should be added to the eCRF.
6.5
Study stopping rules
During the clinical study, planned dosing may be discontinued for all subjects on a dose level, 
but subjects will be required to attend all visits during the Observation Period. Possible reasons 
for discontinuation of a dose level include (but are not limited to):

In the opinion of the DMC, a clinically significant event or a pattern of events occur that 
contraindicate the dosing of any more subjects.

If the DMC judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and Good Clinical Practice (GCP).
More detailed criteria for stopping a dose arm will be defined in the DMC charter.
7
STUDY TREATMENT
7.1
Description of investigational medicinal product
UCB7665 product is supplied as a lyophilized powder in a 10mL Type I glass vial with a rubber 
stopper, sealed with an aluminum overseal and flip-off overcap. Prior to use, the lyophilized 
vials have to be reconstituted with 4mL of diluent (
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 67 of 353
7.2
Treatment to be administered
Subjects in Dose Arm 1 will receive 5 sc doses of UCB7665 4mg/kg at 1-week intervals. 
Subjects in Dose Arm 2 will receive 3 sc doses of UCB7665 7mg/kg at 1-week intervals. 
Subjects in Dose Arm 3 will receive 2 sc doses of UCB7665 10mg/kg at a 1-week interval.
Subjects in Dose Arm 4 will receive 1 sc dose of UCB7665 15mg/kg. 
Subjects in Dose Arm 5 will receive 1 sc dose of UCB7665 20mg/kg.
The IMP will be administered as a sc infusion using an infusion pump:
The perfusor will be programmed at a constant flow rate of 20mL/h for all subjects. In the case 
of any blockage of the infusion, a suitable flush (eg, 0.9% sodium chloride) is allowed.
The subject’s body weight at Screening Visit will be used for the dose calculation. The dose will 
be constant for a subject throughout the duration of the study, and will not be adjusted during the 
treatment. 
The exact procedure for dose preparation according to dose arm and body weight will be 
provided in a pharmacy manual.
The infusion rate may be reduced at any time at the discretion of the investigator. If an infusion 
is interrupted, it can be restarted if the investigator considers it appropriate to do so. The 
chronology of these events should be recorded accurately in the source data and eCRF.
In the event of a severe infusion reaction, the subject must permanently discontinue IMP (see 
Section 12.1.10).
7.3
Packaging
The IMP is manufactured, packaged, and labeled according to Good Manufacturing Practice 
(GMP) guidelines and applicable laws or regulations. The IMP is suitably packaged in such a 
way as to protect the IMP from deterioration during transport and storage.
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Council for 
Harmonisation (ICH) guidelines on GCP and GMP and will include any locally required
statements. If necessary, labels will be translated into the local language.
7.5
Handling and storage requirements
The investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
Investigational medicinal product stored by the investigator is to be kept in a secured area with 
limited access.
Appropriate storage conditions must be ensured either by controlled fridge temperature or by
completion of a temperature log in accordance with local requirements on a regular basis 
(eg, once a day), showing minimum and maximum temperatures reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately communicated to the 
Clinical Project Manager (CPM) (or designee) before further use of the IMP.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 68 of 353
The CPM (or designee) will transmit the out-of-range temperature (copy of the temperature log 
and duration of the out-of-range temperature, if available) to the Clinical Supply Manager or 
designee. Based on discussion with a UCB Quality Assurance representative, the Clinical Supply
Manager or designee will then provide the CPM (or designee) with instructions for the site 
regarding use of the IMP.
7.6
Drug accountability
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any IMP lost (due to breakage or wastage), not used, disposed of at the study site, or returned to 
the sponsor or designee must also be recorded on the appropriate forms. All supplies and 
pharmacy documentation must be made available throughout the study for UCB (or designee) to 
review.
The investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed.
The investigator may assign some of the investigator’s duties for drug accountability at the study
site to an appropriate pharmacist/designee.
The investigator must ensure that the IMP is used only in accordance with the protocol.
Periodically, and/or after completion of the clinical phase of the study, all used (including empty
containers) and unused IMP containers must be reconciled and returned to UCB (or designee), 
preferably in their original package or destroyed on site. Investigational medicinal product 
intended for the study cannot be used for any other purpose than that described in this protocol.
7.7
Procedures for monitoring subject compliance
Drug accountability is ensured by administering the IMP as sc infusion by designated personnel. 
Drug accountability must be recorded on the Drug Accountability form.
7.8
Concomitant medication/treatment
7.8.1
Permitted immunosuppressant medications
The following concomitant immunosuppressant medications are permitted during the course of 
the study at a stable dose.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 69 of 353
Table 7‒1:
Permitted immunosuppressant medications
Permitted medications
Dose
Comment
Oral corticosteroids 
(prednisolone)
≤10mg/day
Stable dose for 2 weeks prior to Baseline
Methotrexate
≤30mg/week
Stable dose for 2 months prior to Baseline
Mycophenolate mofetil
≤3g/day
Stable dose for 2 months prior to Baseline
Cyclosporin
≤5mg/kg/day
Stable dose for 2 months prior to Baseline
Azathioprine
≤3mg/kg/day
Stable dose for 2 months prior to Baseline
Danazol
≤15mg/kg/day
Stable dose for 2 months prior to Baseline
Dapsone
100mg/day
Stable dose for 2 months prior to Baseline
In the event of a subject developing an infection during the course of the study, samples for 
culture will be taken prior to commencing antimicrobial treatment. Antimicrobial treatment may
be modified accordingly when the identity of the infective organism is known.
Vaccines (with the exception of live vaccines) and prophylactic antibiotics are permitted in 
splenectomized subjects.
7.8.2
Prohibited concomitant treatments (medications and therapies)
The following concomitant medications are prohibited during the study:

IVIg

All biologics including rituximab

Cyclophosphamide

Pimecrolimus 

IPP-201101 (Lupuzor™)

PLEX

Immunoadsorption

Anti-D 

TPO-R agonists (eltrombopag, romiplostim)

Dexamethasone

Vinca alkaloids (vincristine, vinblastine)

Anticoagulants and antiplatelets (warfarin, heparin, clopidogrel, aspirin, salicylics,
dipyramidole, prasugrel, tricagrelor, tirofiban, abciximab)
If a subject needs or takes any prohibited medication (except IVIg, PLEX, dexamethasone or 
rituximab), the investigator will (where possible) discuss with the Medical Monitor and a 
decision will be made whether the subject can continue in the study or must be withdrawn. If 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 70 of 353
subject needs IVIg, PLEX, dexamethasone or rituximab, the subject must be withdrawn from the 
study.
7.8.3
Rescue medication
In the case of prolonged hypogammaglobulinemia the subject will be considered for treatment 
with prophylactic antimicrobial therapy. Subjects will be followed up until immunoglobulin 
levels return to within the normal range.
In case of lack of efficacy and/or severe bleeding events and where appropriate, platelet 
substitution or treatment with a commercially available iv immunoglobulin may be considered.
If such rescue medication must be given when the subject is still in the dosing period, the subject 
should be withdrawn from the study treatment and complete all Observation visits, if possible. 
If such rescue medication is given when the subject has completed the study treatment, the 
subject should continue the Observation Visits, as per schedule of study assessments
(Section 5.2). 
7.9
Blinding
This is an open-label study and blinding is not applicable.
7.10
Randomization and numbering of subjects
An IXRS will be used for assigning eligible subjects to a treatment regimen based on a 
predetermined production randomization and/or packaging schedule provided by PAREXEL
Informatics. The IXRS will generate individual assignments for subject kits of IMP, as 
appropriate, according to the dose arm and subject’s weight.
The first 6 subjects (and those treated before DMC assessment after the 6 subjects) will not be 
randomized. Once the DMC has advocated the initiation of Dose Arm 2 for enrollment, 
subsequent subjects will be randomly assigned to 1 of the 2 dose arms (ie, Dose Arm 1 and Dose 
Arm 2) in a 1:1 ratio. Once 15 subjects are enrolled in the Dose Arm 1, the remaining subjects 
will be enrolled in Dose Arm 2 until Dose Arm 2 is completed with 15 subjects.
After Dose Arm 2, there will be no randomization between dose arms.
To enroll a subject (Visit 1), the investigator or designee will contact the IXRS and provide brief 
details about the subject to be enrolled. Each subject will receive a 5-digit number assigned at 
screening that serves as the subject identifier throughout the study. The subject number will be 
required in all communication between the investigator or designee and the IXRS regarding a 
particular subject. Subject numbers and kit numbers will be tracked via the IXRS. 
To randomize a subject, the investigator or designee will contact the IXRS and provide brief 
details about the subject to be randomized. The IXRS will automatically inform the investigator 
or designee of the subject’s kit number. The IXRS will allocate kit numbers to the subject based 
on the subject number or randomization during the course of the study.
8
STUDY PROCEDURES BY VISIT 
A detailed tabular schedule of study procedures is provided in Section 5.2.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 71 of 353
8.1
Screening Period
8.1.1
Visit 1 (Day -28 to -1) Screening Visit (all Dose Arms)
At Visit 1, subjects will be evaluated for their suitability for enrollment. Prior to the conduct of 
any study-related procedures, a complete explanation (both verbal and written) of the nature and 
purpose of the study will be given to the subject by the investigator (or designee). The subject is 
required to sign and date the IRB/IEC-approved Informed Consent form if he/she decides to 
participate in the study.
Subjects will also have the option of providing additional voluntary informed consent for 
collection of whole blood samples for exploratory DNA and RNA analyses.
The subject’s eligibility for the study will be determined on the basis of the inclusion/exclusion 
criteria and signature of an informed consent prior to any study-related procedures or 
evaluations. The following assessments and procedures will be performed during Visit 1 of 
TP0001:

Obtain written informed consent 

Obtain informed consent for substudy involving DNA and RNA analyses

Assessment of inclusion/exclusion criteria

Demographic data (includes date of birth, gender, and race/ethnicity)

General medical and procedure history

ITP history

Prior and concomitant medications 

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Body weight

Height

Physical examination (complete)

12-lead ECG (triplicate)

Karnofsky Performance Status

Recording of AEs

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry (two blood samples for assessment of platelet count to be obtained via 2 
separate blood collections)

Serum pregnancy test for women of childbearing potential

Serum total IgG and IgG subclasses concentration 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 72 of 353

Serum HbA1c

Serology tests for HIV, hepatitis B, and hepatitis C

IGRA TB test

ITP bleeding scale

TB signs and symptoms questionnaire
8.2
Dosing Period for all Dose Arms
8.2.1
Visit 2 (Week 1/Day 1) Baseline Visit
Visit 2 can occur at any time after Visit 1, but no later than 28 days after Visit 1. Prior to dosing
at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value 
will be used to check inclusion criterion. The other platelet sample will be sent to the central 
laboratory.
Eligible subjects will be treated with IMP at Visit 2. 
Subjects allocated to Dose Arm 1 (UCB7665 4mg/kg weekly sc) will receive a total of 5 doses of 
IMP at Visit 2 (Day 1, Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), and 
Visit 7 (Week 5). 
Subjects allocated to Dose Arm 2 (UCB7665 7mg/kg weekly sc) will receive a total of 3 doses of 
IMP at Visit 2 (Day 1, Week 1), Visit 4 (Week 2), and Visit 5 (Week 3). 
Subjects allocated to Dose Arm 3 (UCB7665 10mg/kg weekly sc) will receive a total of 2 doses 
of IMP at Visit 2 (Day 1, Week 1) and Visit 4 (Day 8, Week 2). 
Subjects allocated to Dose Arm 4 (UCB7665 15mg/kg) will receive 1 dose of IMP at Visit 2 
(Day 1, Week 1).
Subjects allocated to Dose Arm 5 (UCB7665 20mg/kg) will receive 1 dose of IMP at Visit 2
(Day 1, Week 1).
The following assessments will be performed at this visit (predose unless stated otherwise):

Reconfirm inclusion/exclusion criteria

Serum platelets for inclusion/exclusion check

Call IXRS to obtain treatment kit number(s)

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature) assessed prior 
to dosing, every 15 minutes during infusion, end of infusion, and 2 and 4 hours after end of 
infusion; respiratory rate to be assessed only once prior to dosing

Recording of AEs (assessed predose, at end of infusion, and at 2 and 4 hours after end of 
infusion)

Subjects in Dose Arms 1 and 2 will stay on site for 4 hours after the end of infusion for 
inpatient observation at the site.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 73 of 353

Subjects in Dose Arms 3, 4 and 5 will stay on site for 6 hours after the end of infusion for 
inpatient observation at the site.

Physical examination (abbreviated)

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Blood sample for the following:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration 

Serum IgA, IgM, and IgE concentration

ITP-specific autoantibodies 

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the inclusion 
criteria of platelet count <35x109/L at Baseline

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Exploratory safety biomarkers
. Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety
biomarkers

Serum BAFF levels

Exploratory biomarker analysis

Serum cytokines mandatory for all subjects at pre-dose, and only in case of infusion 
reactions at 4 hours after end of infusion

Collection of whole blood for exploratory DNA and RNA analyses

ITP bleeding scale

NFI-MS

Administration of IMP

Review withdrawal criteria

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to computed tomography (CT) scan, magnetic resonance imaging
(MRI) and/or lumbar puncture (LP) for cerebrospinal fluid (CSF) collection to be performed 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 74 of 353
if indicated at the discretion of the investigator, considering the local guidelines for 
performing LP in subjects with ITP.
8.2.2
Visit 3 (Week 1/Day 4) [UCB7665 4mg/kg, UCB7665 7mg/kg, and 
UCB7665 10mg/kg]
This is a nondosing visit. A visit window of ±1 day relative to Dose 1 at the Visit 2 date is 
allowed for this visit. The following assessments will be performed at this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

Exploratory safety biomarkers
 only from 
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4)

Review withdrawal criteria

Serum cytokines, only in case of late infusion reactions visible during the visit

For Dose Arm 1, 2, and 3 collection of whole blood for exploratory RNA analyses 

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.2.3
Visit 4 (Week 2/Day 8) [UCB7665 4mg/kg, UCB7665 7mg/kg and 
UCB7665 10mg/kg]
This is the second dosing visit and a window of ±2 days is allowed for this visit, relative to 
Dose 1 at the Visit 2 date. However, there should be a minimum of 5 days and a maximum of 
9 days since the last dosing day. The following assessments will be performed at this visit
(predose unless stated otherwise):

Concomitant medications
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 75 of 353

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature) assessed prior 
to dosing, every 15 minutes during infusion, end of infusion, and 2 and 4 hours after end of 
infusion; respiratory rate to be assessed only once prior to dosing

Recording of AEs (assessed predose, at end of infusion, and at 2 and 4 hours after end of 
infusion)

Subjects in Dose Arms 1 and 2 will stay on site for 4 hours after the end of infusion for 
inpatient observation at the site.

Subjects in Dose Arms 3, 4 and 5 will stay on site for 6 hours after the end of infusion for 
inpatient observation at the site. 

Physical examination (abbreviated)

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory serum 
biomarkers

Serum BAFF levels

Exploratory biomarker analysis

Serum cytokines at pre-dose mandatory for subjects on Dose Arm 3 (10mg/kg), and at 
4 hours after end of infusion (for all dose arms)

For Dose Arm 3, only collection of whole blood for exploratory DNA and RNA analyses

ITP bleeding scale

Administration of IMP

Review withdrawal criteria
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 76 of 353

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.2.4
Visit 5 (Week 3/Day 15) [UCB7665 4mg/kg and UCB7665 7mg/kg]
This is the third dosing visit and a window of ±2 days is allowed for this visit, relative to Dose 1 
at the Visit 2 date. However, there should be a minimum of 5 days and a maximum of 9 days 
since the last dosing day. The following assessments will be performed at this visit (predose 
unless stated otherwise):

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature) assessed prior 
to dosing, every 15 minutes during infusion, end of infusion, and 2 and 4 hours after end of 
infusion; respiratory rate to be assessed only once prior to dosing

Recording of AEs (assessed predose, at end of infusion, and at 2 and 4 hours after end of 
infusion)

Physical examination (abbreviated)

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration 

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Serum IgA, IgM, and IgE concentration (UCB7665 7mg/kg only)

Exploratory safety biomarkers (may include but not limited to:
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety
biomarkers
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 77 of 353

Serum BAFF levels

Exploratory biomarker analysis

For Dose Arm 2 only, collection of whole blood for exploratory DNA and RNA analyses 

ITP bleeding scale

Administration of IMP

Review withdrawal criteria

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.2.5
Visit 6 for Dose Arm 1 (Week 4/Day 22) [UCB7665 4mg/kg only]
This is the fourth dosing visit (UCB7665 4mg/kg only) and a window of ±2 days is allowed for 
this visit, relative to Dose 1 at the Visit 2 date. However, there should be a minimum of 5 days 
and a maximum of 9 days since the last dosing day. The following assessments will be 
performed at this visit (predose unless stated otherwise):

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature) assessed prior 
to dosing, every 15 minutes during infusion, end of infusion, and 2 and 4 hours after end of 
infusion; respiratory rate to be assessed only once prior to dosing

Recording of AEs (assessed predose, at end of infusion, and at 2 and 4 hours after end of 
infusion)

Physical examination (abbreviated)

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following:

Plasma concentration of UCB7665 

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 78 of 353

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety
biomarkers

Serum BAFF levels

Exploratory biomarker analysis

ITP bleeding scale

Administration of IMP

Review withdrawal criteria

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.2.6
Visit 7 for Dose Arm 1 (Week 5/Day 29) [UCB7665 4mg/kg only]
This is the fifth dosing visit (UCB7665 4mg/kg only) and a window of ±2 days is allowed for 
this dosing visit, relative to Dose 1 at the Visit 2 date. However, there should be a minimum of 5 
days and a maximum of 9 days since the last dosing day. The following assessments will be 
performed at this visit (predose unless stated otherwise):
Following assessments will be performed:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature) assessed prior 
to dosing, every 15 minutes during infusion, end of infusion, and 2 and 4 hours after end of 
infusion; respiratory rate to be assessed only once prior to dosing

Recording of AEs (assessed predose, at end of infusion, and at 2 and 4 hours after end of 
infusion)

Physical examination (abbreviated)

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 79 of 353

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

Serum IgA, IgM, and IgE concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety
biomarkers

Serum BAFF levels

Exploratory biomarker analysis

For Dose Arm 1 only, collection of whole blood for DNA and RNA analyses

ITP bleeding scale

Administration of IMP

Review withdrawal criteria

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.3
Telephone Contacts 
For Dose Arms 3, 4 and 5 the site must make a phone call to the subject on Day 1 and Day 2 
after dosing as a safety measure.
8.3.1
Telephone Contact 1 (Week 1/Day 2) [UCB7665 10mg/kg, UCB7665 
15mg/kg, UCB7665 20mg/kg]

Concomitant medications

Concomitant medical procedures

Recording of AEs
8.3.2
Telephone Contact 2 (Week 1/Day 3) [UCB7665 10mg/kg, UCB7665 
15mg/kg, UCB7665 20mg/kg]

Concomitant medications
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 80 of 353

Concomitant medical procedures

Recording of AEs
8.3.3
Telephone Contact 3 (Week 2/Day 9) [UCB7665 10mg/kg only]

Concomitant medications

Concomitant medical procedures

Recording of AEs
8.3.4
Telephone Contact 4 (Week 2/Day 10) [UCB7665 10mg/kg only]

Concomitant medications

Concomitant medical procedures

Recording of AEs
8.4
Observation Period
The Observation Period will last for 8 weeks following the final dose administration. The first 
visit in the Observation Period will be performed 3 days after the final dose administration and 
subsequent visits will be performed at weekly intervals (except for a 2-week interval before the 
final visit). 
For UCB7665 4mg/kg weekly dose (Dose Arm 1), the following visits will be performed: 
Visit 8, Visit 9, Visit 10, Visit 11, Visit 12, Visit 13, Visit 14, and Visit 15, corresponding to 
UCB7665 7mg/kg weekly dose (Dose Arm 2) on Visit 6, Visit 7, Visit 8, Visit 9, Visit 10, 
Visit 11, Visit 12, and Visit 13.
For the UCB7665 10mg/kg weekly dose (Dose Arm 3), the following visits will be performed: 
Visit 5, Visit 6, Visit 7, Visit 8, Visit 9, Visit 10, Visit 11, and Visit 12.
For the UCB7665 15 mg/kg dose (Dose Arm 4) and the UCB7665 20mg/kg dose (Dose Arm 5), 
the following visits will be performed: Visit 3, Visit 4, Visit 5, Visit 6, Visit 7, Visit 8, Visit 9 
and Visit 10.
8.4.1
Visit 8 (Week 5/Day 32) [UCB7665 4mg/kg]/ 
Visit 6 (Week 3/Day 18) [UCB7665 7mg/kg]/
Visit 5 (Week 2/Day 11) [UCB7665 10mg/kg]
Visit 3 (Week 1/Day 4) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the first visit in the Observation Period and will be performed 3 days after the final dose 
of the IMP. A visit window of ±1 day relative to the final dosing visit is allowed for this visit. 
The following assessments will be performed at this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 81 of 353

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665 

Anti-UCB7665 antibodies

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Exploratory safety biomarkers
only from 
subjects experiencing severe headaches or GI disturbances (only in  case of Adverse of 
Interest, see Section 12.4).

Serum total IgG and IgG subclasses concentration

Serum cytokines, only in case of late infusion reactions visible during the visit

For Dose Arm 4 and 5 collection of whole blood for exploratory RNA analyses

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.4.2
Visit 9 (Week 6/Day 36) [UCB7665 4mg/kg ]/ 
Visit 7 (Week 4/Day 22) [UCB7665 7mg/kg]/ 
Visit 6 (Week 3/Day 15) [UCB7665 10mg/kg]
Visit 4 (Week 2/Day 8) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the second visit in the Observation Period. A visit window of ±2 days is applicable for 
this visit relative to the day of the final dosing visit. The following assessments will be 
performed at this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs

Physical examination (abbreviated)

12-lead ECG (triplicate)

Urine sample for urinalysis
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 82 of 353

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Exploratory safety biomarkers
 only from 
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4).

Serum total IgG and IgG subclasses concentration

Serum IgA, IgM, and IgE concentration 

ITP-specific autoantibodies 

ITP bleeding scale

NFI-MS

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.4.3
Visit 10 (Week 7/Day 43) [UCB7665 4mg/kg]/ 
Visit 8 (Week 5/Day 29) [UCB7665 7mg/kg]/
Visit 7 (Week 4/Day 22) [UCB7665 10mg/kg]
Visit 5 (Week 3/Day 15) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the third visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs

Urine sample for urinalysis
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 83 of 353

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies

Exploratory safety biomarkers
, only from 
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4)

Serum BAFF levels

Exploratory biomarker analysis

Serum total IgG and IgG subclasses concentration

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.4.4
Visit 11 (Week 8/Day 50) [UCB7665 4mg/kg]/ 
Visit 9 (Week 6/Day 36) [UCB7665 7mg/kg]/ 
Visit 8 (Week 5/Day 29) [UCB7665 10mg/kg]
Visit 6 (Week 4/Day 22) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the fourth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. The following assessments will be performed at 
this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs

Physical examination (abbreviated)

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Exploratory safety biomarkers
 only from 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 84 of 353
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4)

Serum total IgG and IgG subclasses concentration 

ITP bleeding scale

NFI-MS

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.4.5
Visit 12 (Week 9/Day 57) [UCB7665 4mg/kg]/ 
Visit 10 (Week 7/Day 43) [UCB7665 7mg/kg]/ 
Visit 9 (Week 6/Day 36) [UCB7665 10mg/kg]
Visit 7 (Week 5/Day 29) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the fifth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Exploratory safety biomarkers
, only from 
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4)

Serum total IgG and IgG subclasses concentration

Serum cytokines, only in case of late infusion reactions visible during the visit
REDACTED COPY
visit 
PY 
visit 
er
CO
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COP
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blo
R
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sed to support any marketing authorization application and any extensions or variations thereof.
cedure
ns o
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for per
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This document cannot be u
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UCB7
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a


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 85 of 353

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
8.4.6
Visit 13 (Week 10/Day 64) [UCB7665 4mg/kg]/ 
Visit 11 (Week 8/Day 50) [UCB7665 7mg/kg]/ 
Visit 10 (Week 7/Day 43) [UCB7665 10mg/kg]
Visit 8 (Week 6/Day 36) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the sixth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. The following assessments will be performed at 
this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs

Physical examination (abbreviated)

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Serum total IgG and IgG subclasses concentration

Exploratory safety biomarkers
, only from 
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4)

ITP bleeding scale

NFI-MS

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
REDACTED COPY 
hemat
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ny marketing authorization application and any extensions or variations thereof.
/kg]
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inc
rt any


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 86 of 353
8.4.7
Visit 14 (Week 11/Day 71) [UCB7665 4mg/kg]/ 
Visit 12 (Week 9/Day 57) [UCB7665 7mg/kg]/ 
Visit 11 (Week 8/Day 50) [UCB7665 10mg/kg]
Visit 9 (Week 7/Day 43) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the seventh visit in the Observation Period. A visit window of ±2 days is applicable for 
this visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies

Exploratory safety biomarkers
 only from 
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4)

Serum BAFF levels

Exploratory biomarker analysis

Serum total IgG and IgG subclasses concentration

Serum IgA, IgM, and IgE concentration

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 87 of 353
8.4.8
End-of-Study Visit: Visit 15 (Week 13/Day 85) [UCB7665 4mg/kg]/ 
Visit 13 (Week 11/Day 71) [UCB7665 7mg/kg]/
Visit 12 (Week 10/Day 64) [UCB7665 10mg/kg]
Visit 10 (Week 9/Day 57) [UCB7665 15mg/kg and UCB7665 20mg/kg]
The End-of-Study Visit will be conducted 8 weeks after the final dose. A visit window of 
±2 days is applicable for this visit relative to the day of the final dosing visit. The following 
assessments will be performed at this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Body weight

Recording of AEs

Physical examination (complete)

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

ITP-specific autoantibodies 

For all dose arms, collection of whole blood for exploratory RNA analyses 

ITP bleeding scale

NFI-MS

Subject exit interview

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.

TB signs and symptoms questionnaire
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 88 of 353
8.5
Early Withdrawal Visit
All subjects who withdraw early from the study treatment should attend an Early Withdrawal 
Visit which will be scheduled as close as possible to the date of the decision for the study or 
treatment withdrawal. Subjects are encouraged to return to the clinic for all visits of the
Observation Period following the Early Withdrawal Visit. The subjects will have their 
End-of-Study Visit scheduled 8 weeks after their final dose. 
In case a subject is not willing to attend the visits in the Observation Period, the subjects should 
still be strongly encouraged to attend at least the Early Withdrawal Visit and End-of-Study Visit. 
The End-of-Study Visit should be scheduled 8 weeks after their last dose of IMP.
The assessments to be done at both the Early Withdrawal Visit as well as the End-of-Study Visit 
are the same as those at Visit 15 for the UCB7665 4mg/kg weekly (Dose Arm 1) group, Visit 13 
for the UCB7665 7mg/kg weekly (Dose Arm 2) group, Visit 12 for the UCB7665 10mg/kg 
weekly (Dose Arm 3) group, or Visit 10 for the UCB7665 15mg/kg (Dose Arm 4) and UCB7665 
20mg/kg (Dose Arm 5) groups, except for the subject exit interview which will be performed at 
the End-of-Study Visit only.
8.6
Unscheduled Visit
Unscheduled visits may include the following assessments or other assessments deemed 
necessary by the investigator:

Concomitant medication

Concomitant medical procedures

Recording of AEs

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature)

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment. Additionally, other diagnostic procedures including but not limited 
to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion 
of the investigator, considering the local guidelines for performing LP in subjects with ITP.
Other safety assessments (eg, physical examination, 12-lead ECG, laboratory assessments) may
be performed at the discretion of the investigator.
In the event of a subject developing an infection during the course of the study, samples for 
culture will be taken prior to commencing antimicrobial treatment.
9
ASSESSMENT OF EFFICACY
9.1
Platelet counts
For assessment of platelet counts, blood samples will be collected by qualified site personnel at 
the same time that samples are collected for standard clinical laboratory assessments. The time 
and date of the blood draws will be recorded in medical source data and the eCRF. Assessment 
will be performed according to the schedule of study assessments (Section 5.2).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 89 of 353
Platelet counts will be determined by a central laboratory and the following variables will be 
computed in the statistical database for the purpose of analysis:

Response by visit and Response at least once during the study

Complete Response by visit and Complete Response at least once during the study

Platelet count ≥50x109/L by visit and at least once during the study

Value and change from Baseline in platelet count by visit

Baseline-corrected AUEC for platelet count calculated from Baseline to the end of study visit

Maximum value and maximum increase from Baseline

Time to Response

Time to Complete Response

Time to achieving platelet count ≥50x109/L

Duration of Response

Duration of Complete Response

Duration of platelet count ≥50x109/L

Clinical Response: platelet count ≥30x109/L and at least 2-fold increase from Baseline value 
and absence of bleeding

Time to Clinical Response: time from starting treatment to achievement of Clinical Response

Duration of Clinical Response: measured from achievement of Clinical Response to loss of 
Clinical Response (loss of Clinical Response defined as platelet count <30x109/L or less than 
2-fold increase from Baseline platelet count or presence of bleeding)

Complete Clinical Response: platelet count ≥100x109/L and absence of bleeding

Time to Complete Clinical Response: time from starting treatment to achievement of 
Complete Clinical Response

Duration of Complete Clinical Response: measured from achievement of Complete Clinical 
Response to loss of Complete Clinical Response (loss of Complete Clinical Response defined 
as platelet count <100x109/L or presence of bleeding)

No Clinical Response: platelet count <30x109/L or less than 2-fold increase from Baseline or 
presence of bleeding
The clinical response variables will be assessed only for visits for which both platelet counts and 
the ITP bleeding score are assessed (with the exception of the confirmatory platelet assessments 
which may be obtained at any visit [scheduled or unscheduled] provided that they meet the 
criteria below). In order to define a clinical response, the platelet count must be confirmed on 2 
separate occasions at least 7 days apart (ie, the second assessment should be ≥168 hours after the 
first assessment). The time to response will be taken as the time to the first platelet assessment 
(obtained at the same time as the corresponding ITP bleeding score assessment). If the second 
assessment does not fulfill the required criteria for a clinical response, the subject will be 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 90 of 353
considered as a nonresponder at the respective visits. In order to define a clinical response (or no 
clinical response), the platelet count must be confirmed on 2 separate occasions; further details 
will be provided in the SAP. Absence of bleeding is indicated by Grade 0 for all domains of the 
SMOG. Presence of bleeding is indicated by a Grade of 1 or above, for at least one domain of the 
SMOG.
Refer to Section 14 for details of statistical analysis of these variables.
9.2
ITP bleeding score
The International Working Group on ITP now proposes a consensus-based ITP-specific Bleeding 
Assessment Tool (ITP-BAT), based on a precise definition of bleeding manifestations and on the 
grading of their severity (Rodeghiero et al, 2013). The ITP bleeding score will be assessed using 
the ITP-BAT tool version 1.0. Assessment will be performed according to the schedule of study
assessments (Section 5.2).
For the ITP-BAT, bleeding manifestations were grouped into 3 major domains: skin (S), visible 
mucosae (M), and organs (O), with gradation of severity (SMOG). Each bleeding manifestation 
is assessed at the time of examination. Severity is graded from 0 to 3 or 4, with grade 5 for any
fatal bleeding. Bleeding reported by the subject without medical documentation is graded 1. 
Within each domain, the same grade is assigned to bleeding manifestations of similar clinical 
impact. The “worst” bleeding manifestation since the last Observation Period visit is graded, and 
the highest grade within each domain is recorded. The SMOG system provides a consistent 
description of the bleeding phenotype in ITP.
A standardized data collection form will be used to facilitate collection of information and 
communication among physicians and investigators. The grading of bleeding symptoms at 
presentation and at each subsequent evaluation is presented in Appendix 18.2.
9.3
Patient reported outcomes
Subjects will complete 1 questionnaire (NFI-MS) and 1 subject exit interview as per time points 
mentioned in the schedule of study assessments in Section 5.2. Administration of the 
questionnaire and the subject exit interview should be performed by study personnel other than 
the treating physician. The questionnaire and the subject exit interview should be completed in a 
quiet place and by the subject themselves.
The questionnaire and the subject exit interview should be completed in the following order:
NFI-MS followed by the subject exit interview which will be performed only at last visit. The 
questionnaire and the subject exit interview should only be checked for completeness. On dosing 
days, the NFI-MS questionnaire will be completed prior to dosing.
9.3.1
NFI-MS
The NFI-MS was developed in multiple sclerosis and consists of 23 items in 4 subscales of 
Physical (8 items), Cognitive (4 items), Relief by diurnal sleep or rest (6 items) and Abnormal 
nocturnal sleep and sleepiness (5 items). A summary score is available comprising items from 
the Physical and Cognitive subscales. The measurement properties have been established using 
Rasch analysis (Mills et al, 2013; Mills et al, 2010).
Each item has a 4 point, Likert response option. There is a single sentence instruction at the start 
of the scale asking respondents to consider their experience over the previous 2 weeks.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 91 of 353
Using the interval level NFI-MS scores, the largest minimal clinically important difference 
(MCID) equated to 2.49 points on the Summary scale, 2.36 points on the Physical scale, 
0.84 points on the Cognitive scale, 0.97 on the Diurnal Sleep scale and 1.95 on the Nocturnal 
Sleep scale (Mills et al, 2013). The NFI-MS questionnaire is available as Appendix 18.3.
9.4
Subject exit interview
At the last clinic visit, subject interview will be conducted using a semi-structured interview 
guide by a study nurse/study personnel. The aim is to collect the subject's experience with living 
with ITP in terms of symptoms and impact on daily activities, and the perceived changes during 
the course of the study. In addition, the relevance of the NFI-MS in ITP will be assessed. The 
interviews will be recorded. If a subject leaves the study prematurely, he/she will also be invited 
to participate in an exit interview.
10
ASSESSMENT OF PHARMACOKINETIC/ 
PHARMACODYNAMIC VARIABLES
10.1
Pharmacokinetic variables
The plasma concentration of UCB7665 will be characterized. Blood samples will be drawn 
according to the schedule of study assessments Section 5.2
All blood samples will be collected before dosing with UCB7665 at the dosing visits, and will be 
drawn at the same time of the sampling for standard clinical laboratory tests. The time and date 
of collection will be recorded in the eCRF.
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study.
10.2
Pharmacodynamic variables
For all PD assessments, blood samples will be collected predose (at dosing visits) by qualified 
site personnel at the same time that samples are collected for standard clinical laboratory
assessments. Blood samples for PD analyses will be drawn according to the schedule of study
assessments (Section 5.2). The time and date of collection will be recorded in the eCRF. 
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study.

Serum IgG concentrations

Serum IgG subclass concentrations 

Serum ITP-specific autoantibody
11
ASSESSMENT OF OTHER IMMUNOLOGICAL VARIABLES
For all immunological assessments, blood samples will be collected predose (at dosing visits) by
qualified site personnel at the same time that samples are collected for standard clinical 
laboratory. The time and date of the blood draws will be recorded in the eCRF. The following 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 92 of 353
immunological assessments will be performed according to the schedule of study assessments 
(Section 5.2).

Serum immunoglobulin concentration over time

IgA

IgE

IgM

Serum complement levels over time

C3

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
Plasma complement levels over time

C3a

C5a

Exploratory safety biomarkers levels over time

Serum BAFF levels

Lymphocyte counts (B and T)

Anti-UCB7665 antibodies

Cytokines
Cytokine samples will be taken at Baseline Visit for all subjects. At subsequent visits, 
cytokine samples will be taken only when the subject experiences infusion reactions.
12
ASSESSMENT OF SAFETY
12.1
Adverse events
12.1.1
Definition of adverse event
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the eCRF even if no IMP was taken but specific 
study procedures were conducted. This includes all AEs not present prior to the initial visit and 
all AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
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Page 93 of 353
increases in a clinically significant manner as compared to the clinical profile known to the 
investigator from the subject’s history or the Baseline Period.
Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2 bleeding events
should not be reported as an AE since these events will be assessed and reported during the 
ITP-BAT assessment; CTCAE grade 3 or more bleeding events should be reported as AEs. 
Treatment-emergent AEs are defined as AEs starting after the time of first IMP administration up 
to and including 8 weeks after the final dose.
12.1.2
Procedures for reporting and recording adverse events
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
12.1.3
Description of adverse events
When recording an AE, the investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Signs and symptoms should only be documented as 
AEs in case the underlying disease or condition is unknown or they are considered as clinically
significant independent of the underlying disease or condition in the discretion of the 
investigator. Any discrepancies between the subject’s own words on his/her own records 
(eg, diary card) and the corresponding medical terminology should be clarified in the source 
documentation.
For recording an AE, CTCAE will be used, and only if it is impossible to assess severity using
CTCAE, then AE intensity will be assessed using a scale of mild, moderate, or severe.
Details for completion of the AE eCRF (including judgment of relationship to IMP) are 
described in the CRF Completion Guidelines.
12.1.4
Follow up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the investigator determines 
that it is no longer clinically significant, or the subject is lost to follow up. 
If an AE is ongoing at the end of the study for a subject, follow up should be provided until 
resolution/stable level of sequelae is achieved, or until the investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow up. If no follow up is provided, the 
investigator must provide a justification. The follow up will usually be continued for 8 weeks
after the subject has discontinued his/her IMP.
12.1.5
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:

The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”

The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
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UCB
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 94 of 353
12.1.6
Pregnancy
If an investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the investigator must immediately notify UCB’s Patient Safety (PS) department by providing the 
completed Pregnancy Report and Outcome form (for contact details see Serious Adverse Event 
reporting information at the beginning of this protocol). The subject should be withdrawn from 
the study as soon as pregnancy is known (by positive pregnancy test), and the following should 
be completed:

The subject should return for an Early Withdrawal Visit.

No further IMP will be administered.

An End-of-Study Visit should be scheduled 8 weeks after the subject has discontinued her 
IMP.
The investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
The pregnancy will be documented on the Pregnancy Report and Outcome form provided to the 
investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome form in which the investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to 
follow the health of the child for 30 days after birth for any significant medical issues. In certain 
circumstances, UCB may request that follow up is continued for a period longer than 30 days. If 
the subject is lost to follow up and/or refuses to give information, written documentation of 
attempts to contact the subject need to be provided by the investigator and filed at the site. 
UCB’s PS department is the primary contact for any questions related to the data collection for 
the pregnancy, eventual birth, and follow up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent form that has been approved by the responsible IRB/IEC and should 
be available in the investigator site file. In case of questions about the consent process, the 
investigator may contact the UCB/contract research organization (CRO) contract monitor for the 
study. The investigator will complete the Pregnancy Report and Outcome form and send it to 
UCB’s PS department (for contact details see Serious Adverse Event reporting information at the 
beginning of this protocol) only after the partner has agreed that additional information can be 
captured and has provided the signed Partner Pregnancy Consent form. UCB’s PS department is 
also the primary contact for any questions related to the data collection for the partner pregnancy, 
eventual birth, and follow up.
A pregnancy becomes a serious adverse event (SAE) in the following circumstances: 
miscarriage, abortion (elective or spontaneous), unintended pregnancy after hormonal 
contraceptive failure (if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal 
demise, or any congenital anomaly/birth defect of the baby. Those SAEs must be additionally
reported using the Investigator SAE Report form.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 95 of 353
12.1.7
Suspected transmission of an infectious agent via a medicinal 
product
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the CRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent.
12.1.8
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the appropriate module of the eCRF. Any SAE or nonserious AE associated with 
excessive dosing must be followed as any other SAE or nonserious AE. These events are only 
considered AEs or SAEs if there are associated clinical signs and symptoms or if the act of 
taking the excess medicine itself is an AE or SAE (eg, suicide attempt).
12.1.9
Safety signal detection
The safety variables and ADA results available after 7 days of the final dose of 3 and 6 subjects 
in the UCB7665 4mg/kg weekly group (Dose Arm 1) will be reviewed by the DMC (interim 
analysis 1 and 2) comprising at least 1 external expert, the UCB study physician, the UCB PS
representative, and a biostatistician and will be summarized on an ongoing basis during the study 
so as to continuously evaluate the safety of subjects. The DMC will meet and reach a decision on 
whether or not the study can continue as planned, and whether or not Dose Arm 2 can be started.
Subsequently, safety variables and ADA results available after 7 days of the final dose of 3 and 
6 subjects in the UCB7665 7mg/kg weekly (Dose Arm 2) (together with all available data from 
Dose Arm 1 and 2) will be reviewed by the DMC (interim analysis 3 and 4). The DMC will also 
meet and review safety data to add additional subjects to subsequent dose arms or to open 
subsequent dose arms. Further details are described in Section 5.1.
The DMC may also decide to reduce the number of doses in each of the dose arms, to stop a dose 
arm or not to open a dose arm based on review of data during the study.
Thus, selected data from this study will be reviewed periodically to detect as early as possible 
any safety concern(s) related to the IMP so that investigators, clinical study subjects, regulatory
authorities, and IRBs/IECs will be informed appropriately and as early as possible.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory or ECG results) for which data will be periodically reviewed during the course 
of the study.
12.1.10
Hypersensitivity and adverse reactions
In the event of a severe infusion reaction, the subject must permanently discontinue IMP and be 
managed as described in Appendix 18.4.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 96 of 353
In case of occurrence of a hypersensitivity reaction (except for local injection site reaction) and 
depending upon its severity, appropriate countermeasures will immediately be taken by the 
investigator. The cytokine samples must be taken for infusion reactions.
If the investigator does not initially choose to discontinue the infusion of IMP and symptoms 
persist or escalate during continued infusion, the infusion should be stopped. In case of any 
severe infusion reaction(s), the infusion of IMP must be stopped immediately and appropriate 
treatment initiated, as necessary, at the discretion of the investigator and in accordance with the 
standard of care.
Suspected anaphylactic reactions should be diagnosed using Sampson’s Criteria (Sampson et al, 
2006) as described in Appendix 18.5. In the event of an anaphylactic reaction the infusion must
be discontinued immediately and emergency resuscitation measures implemented. 
12.1.11
Management of severe headache
Severe headache is defined as severe pain limiting self-care activities of daily living (ADL) or 
new/prolonged hospitalization for management of headache or life-threatening consequences 
requiring urgent medical intervention. Self-care ADL refer to bathing, dressing and undressing, 
feeding self, using the toilet, taking medications. Treatment of headache will be provided as 
clinically indicated according to the local guidelines.
Subjects experiencing severe headache will complete the Headache Questionnaire and will 
complete the questionnaire daily until resolution (ie, if headache becomes moderate or mild, 
normal collection of AEs should apply); this assessment will be followed by a neurological 
assessment (including fundoscopy). Further workup will be performed at the discretion of the 
investigator and may include eg, a CT scan, MRI and/or a LP for CSF collection, considering the 
local guidelines for performing LP in patients with ITP. These investigations will be performed 
in order to further understand the mechanism of headache in these subjects.
Details of neurological examination to be performed are provided in Section 12.8.5. The 
Headache Questionnaire is available in Appendix 18.6.
12.1.12
Management of moderate or severe diarrhea
Moderate or severe diarrhea is defined as an increase of ≥4 stools per day over Baseline or 
incontinence due to urgency of diarrhea or new/prolonged hospitalization for management of 
diarrhea or limiting self-care ADL or life-threatening consequences requiring urgent medical 
intervention.
Stool collection and analysis will be performed for subjects reporting moderate or severe 
diarrhea. The frequency of stool sampling will be as clinically indicated in the opinion of the 
investigator. Analysis of stool samples will be performed locally. 
Treatment of diarrhea will be provided as clinically indicated according to the local guidelines.
12.2
Serious adverse events
12.2.1
Definition of serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:

Death
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 97 of 353

Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)

Significant or persistent disability/incapacity

Congenital anomaly/birth defect (including that occurring in a fetus)

Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious
(Important medical events may include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse.)

Initial inpatient hospitalization or prolongation of hospitalization
(A subject admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.)
12.2.2
Procedures for reporting serious adverse events
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by
the site (see contact information for SAE reporting listed in the Serious Adverse Event Reporting 
section at the front of the protocol). The investigator must forward to UCB (or its representative) 
a duly completed “Investigator SAE Report Form for Development Drug” (SAE Report form) 
provided by UCB, even if the data are incomplete, or if it is obvious that more data will be 
needed in order to draw any conclusions. Information recorded on this form will be entered into 
the global safety database.
An Investigator SAE Report form will be provided to the investigator. The Investigator SAE 
Report form must be completed in English. 
It is important for the investigator, when completing the SAE Report form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the investigator is very important for UCB to consider in assessing the safety of the IMP 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 98 of 353
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE Report form.
The investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects of 
the need to inform the investigator of any SAE within this period. Serious AEs that the 
investigator thinks may be associated with the IMP must be reported to UCB regardless of the 
time between the event and the end of the study.
Upon receipt of the SAE Report form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the Investigator’s 
Brochure.
12.2.3
Follow up of serious adverse events
An SAE should be followed until it has resolved, has a stable sequelae, the investigator 
determines that it is no longer clinically significant, or the subject is lost to follow up. 
Information on SAEs obtained after clinical database lock will be captured through the PS 
database without limitation of time.
12.3
Adverse events of special interest
An AE of special interest is any AE that a regulatory authority has mandated to be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
Adverse event of special interest for UCB7665 is:

Potential Hy’s law cases
Potential Hy’s law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN bilirubin in the 
absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, must 
always be reported to UCB as an AE of special interest (ie, without waiting for any additional 
etiologic investigations to have been concluded). Follow-up information should then be reported 
if an alternative etiology is identified during investigation and monitoring of the subject.
12.4
Adverse events of interest
For UCB7665, AEs of interest that require immediate reporting to UCB are:

Severe headache

Moderate to severe diarrhea

Moderate to severe abdominal pain

Moderate to severe vomiting
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 99 of 353
12.5
Immediate reporting of adverse events
The following AEs must be reported immediately using the SAE Report Form according to the 
procedure in Section 12.2.2:

SAE: AE that the investigator classifies as serious by the above definitions regardless of 
causality

Suspected transmission of an infectious agent via a medicinal product

AE of special interest (see Section 12.3)

AE of interest (see Section 12.4)

Confirmed LTB, active TB, and NTBI (see Section 12.8.1)
12.6
Anticipated serious adverse events
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
occur in the population studied in this protocol at some frequency that is independent of drug 
exposure. This original list will remain in effect for the duration of the protocol.
This list does not change the investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 12.2.2.
Table 12‒1: Anticipated serious adverse events for ITP population
Headache
Infections
Bleeding events
12.7
Laboratory measurements
Blood and urine specimens for routine assay of hematology including coagulation parameters, 
clinical chemistry, urinalysis testing, and pregnancy testing as well as serology testing will be 
performed according to the Schedule of assessments (Section 5.2) to monitor the safety of 
subjects. All clinical chemistry, hematology, and urinalysis parameters will be assessed by the 
designated central laboratory with the exception of platelet count and the urine pregnancy test 
prior to each dose. Specific details regarding the handling and processing of serum chemistry, 
hematology, and urinalysis samples are provided in the study laboratory manuals. 
Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally 
and the value will be used to check inclusion criteria. The other platelet sample will be sent to 
the central laboratory. At subsequent dosing visits, an additional platelet sample will be obtained 
prior to dosing and analyzed locally to evaluate withdrawal criterion of platelet count 
>350x109/L. The urinalysis for pregnancy testing will be performed with a dipstick.
The following laboratory parameters will be measured:
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Clinical Study Protocol
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TP0001
Confidential
Page 100 of 353
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Coagulation 
parameters
Urinalysis
Pregnancy test
Basophilsa
Calcium
INR 
pH
Urineb HCG
Eosinophilsa
Phosphate
Prothrombin time
Protein
Serum
c HCG
Neutrophilsa
Chloride
aPTT
Creatinine 
Lymphocytesa
Magnesium
Fibrinogen
Glucose
Others
Monocytesa
Potassium
Ketones
HbA1c
Hematocrit
Sodium
Urobilinogen
HIV
Hemoglobin
BUN
Bilirubin
Hepatitis B
(HBsAg, anti-HBs,
anti-HBc)
Platelet count
AST
Blood
Hepatitis C
(anti-HCV)
RBC count
ALT
Nitrite
Tuberculosisd
WBC count
GGT
Albumin
Total bilirubin 
Leucocytes
Safety Biomarkerse
Direct bilirubin (if 
indicated)
LDH
Total cholesterol
Triglycerides
ALP
Total protein
Albumin
α1-globulin, 
α2-globulin, 
β-globulin, γ-globulin
Creatinine
hs-CRP
Amylase
a Absolute as well as percentages for the differential leucocyte counts will be performed.
ALP=alkaline phosphatase; ALT=alanine aminotransferase; anti-HBc=hepatitis B core antibody; anti-HBs=hepatitis B surface 
antibody; anti-HCV=hepatitis C virus antibody; aPTT=activated partial thromboplastin time; AST=aspartate aminotransferase; 
BUN=blood urea nitrogen;GGT=gamma-glutamyltransferase; HbA1c=glycosylated hemoglobin; HBsAg=hepatitis B surface 
antigen; HCG=human chorionic gonadotropin; HIV=human immunodeficiency virus; hs-CRP=high-sensitivity C-reactive 
protein; INR=International Normalized Ratio; LDH=lactate dehydrogenase; RBC=red blood cell; WBC=white blood cell 
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Clinical Study Protocol
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Page 101 of 353
b Urine pregnancy test will be performed predose on dosing days and at End-of-Study Visit.
c Serum pregnancy test is done at Visit 1 (Screening) and to confirm results of positive urine test if applicable.
d Interferon-gamma release assay by central laboratory.
e May include but not limited to the biomarkers listed in the table. Samples collected for safety biomarkers at Baseline (Visit 2) 
and 4 hours post dosing (Visit 2) for all subjects and during follow up only in subjects with severe headache and/or moderate to 
severe GI disturbances. The Baseline samples will only be analysed in case he subject experienced a severe headache and/or 
moderate to severe GI disturbance.
12.7.1
Evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 6.4, with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as an AE and reported to the study site and sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s law must be 
reported as an AE of special interest (see Section 12.3), and, if applicable, also reported as an 
SAE (see Section 12.2.2).
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 12-3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 12.7.1.1). The local 
hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. Additional investigation and monitoring may be required and adapted based 
on the diagnosis after the cause of the liver injury/abnormality is confirmed (details in 
Section 12.7.1.4). 
The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and sponsor.
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result.
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 2 
laboratory tests are significantly different. Data from the local and central laboratory are to be
recorded on the applicable CRF pages.
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable alternative.
When IMP is stopped due to PDILI (as described in Section 6.4), IMP must be permanently 
discontinued unless a subsequent alternative diagnosis fully explains the hepatic findings. If a 
subsequent alternative diagnosis fully explains the hepatic findings, and the requirements 
provided in Section 12.7.1.2.1 are met, rechallenge with IMP may be appropriate. 
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
The table below summarizes the approach to investigate PDILI.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 102 of 353
Table 12-3: Required investigations and follow up for PDILI 
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULN
b
NA
Hepatology consultc
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP.
Immediate, permanent 
IMP discontinuation.
Essential: Must have 
repeat liver chemistry 
values and additional 
testing completed 
ASAP (see 
Section 12.7.1.3); 
recommended to 
occur at the site with 
HCP.
Monitoring of liver 
chemistry values at least 
twice per week until 
values normalize, 
stabilize, or return to 
within Baseline values.d
≥3xULN
NA
Yes
Immediate, temporary 
or permanent, IMP 
discontinuation.
≥3xULN 
(and ≥2x 
Baseline) 
and 
<5xULN
<2xULN
No
Discussion with Medical 
Monitor required if the 
criterion that allows for 
IMP continuation is met.
Further investigation –
immediate IMP 
discontinuation not 
required (see 
Section 12.7.1.2).
Not required unless 
otherwise medically 
indicated (at 
discretion of 
investigator).
≥5xULN 
(and ≥2x 
Baseline) 
<2xULN
No
Discussion with Medical 
Monitor required.
Hepatology consult 
required if ALT or AST 
≥8xULN.
Immediate, permanent 
IMP discontinuation.
Essential: Every 
attempt must be made 
to have repeat liver 
chemistry values and 
additional testing 
completed within 
48 hours at the site 
with HCP (see 
Section 12.7.1.3).
Monitoring of liver 
chemistry values at least 
twice per week until 
values normalize, 
stabilize, or return to 
within Baseline values. d
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 103 of 353
Table 12-3: Required investigations and follow up for PDILI 
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause).
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
c Details provided in Section12.7.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of potential
hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d Unless an alternative monitoring schedule is agreed by the investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
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UCB
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 104 of 353
12.7.1.1
Consultation with Medical Monitor and local hepatologist
Potential drug-induced liver injury events require notification of the Medical Monitor within 
24 hours (eg, by laboratory alert), and the subject must be discussed with the Medical Monitor as 
soon as possible. If required, the subject must also be discussed with the local hepatologist. The 
local hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. If determined necessary, this discussion should be followed by a full 
hepatology assessment (see Section 12.7.1.3) and SAE report (if applicable).
12.7.1.2
Immediate action: determination of IMP discontinuation
All PDILI events require immediate action, testing, and monitoring. 
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.4 and Table 12-3 for details).
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. The investigator should also consider dose 
reduction for medically necessary concomitant medication and consider changing any medically 
required concomitant medication known to be hepatotoxic to a suitable alternative.
12.7.1.2.1
IMP restart/rechallenge (if applicable)
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Subjects who are immediately discontinued from IMP due to having met certain criteria for 
PDILI (as described in Section 6.4 and Table 12-3), but for whom an alternative diagnosis is 
confirmed, can rarely restart IMP. Rechallenge with IMP can occur only if ALL of the following 
requirements are met:

The results of additional testing and monitoring described in Section 12.7.1.3 and 
Section 12.7.1.4 confirm a nondrug-related cause for the abnormal hepatic laboratory
parameters and any associated symptoms (ie, a subsequent alternative diagnosis fully
explains the hepatic findings). 

No alternative treatment options are available to the subject.

The subject has shown clear therapeutic benefit from the IMP.

Subject’s ALT or AST elevations do not exceed ≥3xULN.

Subject’s total bilirubin is < 1.5xULN.

Subject has no signs or symptoms of hypersensitivity. 

The rechallenge is approved by the UCB responsible physician, DMC, and a hepatologist. 
The hepatologist must be external to UCB but may be a member of the DMC. It is 
recommended that the hepatologist be a local hepatology expert or the hepatologist treating 
the subject.

Subject agrees to the investigator-recommended monitoring plan.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 105 of 353
12.7.1.3
Testing: identification/exclusion of alternative etiology
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP are detailed in 
Table 12-4 (laboratory measurements) and Table 12-5 (additional information). Results of the 
laboratory measurements and information collected are to be submitted to the sponsor on the 
corresponding CRF. If the medical history of the subject indicates a requirement for other 
assessments not included below, these should be completed and submitted, as applicable.
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory.
The following measurements are to be assessed:
Table 12-4: PDILI laboratory measurements
Virology-related
Hematology
Hepatitis A IgM antibody
Eosinophil count
HBsAg
Urinalysis
Hepatitis E IgM antibody
Toxicology screen
HBcAb-IgM
Chemistry
Hepatitis C RNA
Amylase
Cytomegalovirus IgM antibody
If total bilirubin ≥1.5xULN, obtain fractionated 
bilirubin to obtain % direct bilirubin
Epstein-Barr viral capsid antigen IgM antibody 
(if unavailable, obtain heterophile antibody or 
monospot testing)
Serum CPK and LDH to evaluate possible 
muscle injury causing transaminase elevation
Immunology
Additional
Anti-nuclear antibody (qualitative and 
quantitative)
Prothombin time/INRa
Anti-smooth muscle antibody (qualitative and 
quantitative)
Serum pregnancy test
Type 1 anti-liver kidney microsomal antibodies 
(qualitative and quantitative)
PK sample
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; HBsAg=hepatitis 
B surface antigen; IgM=immunoglobulin; INR=international normalized ratio; LDH=lactate dehydrogenase; PDILI=potential 
drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; ULN=upper limit of normal
a.Measured only for subjects with ALT or AST >5 xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; 
hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative cause).
The following additional information is to be collected:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 106 of 353
Table 12-5: PDILI information to be collected
New or updated information
Concomitant prescription and over-the-counter medications (eg, acetaminophen, herbal 
remedies, vitamins); dosages and dates should be included.
Pertinent medical history, including the following:

History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other 
“fatty liver disease”)

Adverse reactions to drugs

Allergies

Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 
antitrypsin deficiency)

Recent travel 

Progression of malignancy involving the liver (Note: Metastatic disease to the liver, by 
itself, should not be used as an explanation for significant AST and/or ALT elevations.)
The appearance or worsening of clinical symptoms of hepatitis or hypersensitivity (eg, fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, decreased appetite, abdominal pain, 
jaundice, fever, or rash)
Recent clinically significant hypotension or hypoxemia with compromised cardiopulmonary
function
Alcohol and illicit drug use; include dates where available
Results of liver imaging or liver biopsy, if done
Results of any specialist or hepatology consult, if done
Any postmortem/pathology reports
ALT=alanine aminotransferase; AST=aspartate aminotransferase; PDILI=potential drug-induced liver injury
12.7.1.4
Follow-up evaluation
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 12-3. Monitoring should continue until liver chemistry values normalize, stabilize, or 
return to Baseline. Determination of stabilization is at the discretion of the investigator in 
consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
12.8
Other safety measurements
12.8.1
Assessment and management of TB and TB risk factors
With the currently available data, TB is not considered as an important potential or identified risk 
for treatment with UCB7665. As immunomodulation may carry a risk of new or activation of 
latent TB, UCB has conservatively developed TB detection and management procedures taking 
into account the most current recommendations of international guidelines (2010 WHO) and 
most recent literature, covering any infection by the mycobacteria tuberculosis complex. 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 107 of 353
Appropriate rigorous precautions are being taken within this protocol to monitor for the risk of 
TB infection prior to study entry and during the study (see Section 6.2.2 (Exclusion Criterion 
#25) and Section 6.4. Following are the key considerations of these procedures:
12.8.1.1
TB Tests at Screening
The IGRA and TB questionnaire are required as indicated in Schedule of Assessments. 

TB screening is mandatory both before study entry and during the conduct of the study. The 
preferred screening test is IGRA performed at a Central Laboratory.
-
The IGRA result must be negative for subjects to enroll in this study
-
Subjects who test positive for IGRA test should be excluded from the study and 
referred for appropriate medical evaluation according to the local medical practice 
guidelines. 
-
If the result of the IGRA test is indeterminate, the particular IGRA test previously
performed may be repeated once; if positive or indeterminate on retest, the subject 
may not be randomized to study drug and, if already randomized, must undergo 
appropriate study specified withdrawal procedures. The retest must be done during 
the protocol-defined Screening window.
12.8.1.2
Monitoring for TB during the study
Subjects will be monitored for signs/symptoms of TB using routine pharmacovigilance measures 
for Adverse Events. Subjects reporting AEs related to signs/symptoms of TB will be evaluated 
for LTB and active TB according to the local medical practice guidelines. 
Subjects with confirmed LTB or active TB or NTMBI will be immediately withdrawn from the 
study as described in Withdrawal Criteria. Confirmed LTB, active TB and NTMBI must be 
reported to the Sponsor immediately regardless of seriousness using the SAE Report Form. 
Additional information received by the Investigator should be provided within 24 hours of 
awareness.
Once withdrawn from study treatment, subjects should return for the End of Study (EOS), 
complete all early withdrawal assessments, and complete the follow-up visits.
12.8.1.3
TB tests at Final /End of Study Visit
Subjects will be evaluated for signs and symptoms of latent or active TB infection and for risk 
factors of exposure to TB, using the TB questionnaire, at the Final/EOS Visit. See the ‘TB signs 
and symptoms questionnaire’ section for further instructions on using the questionnaire.
12.8.1.4
Signs and symptoms of Tuberculosis
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the subject’s history. 
Common symptoms with which the subject may present with include cough, blood in sputum, 
night sweats, lymphadenitis, joint pain/swelling, spinal deformity, headache/confusion, 
abdominal pain mimicking inflammatory bowel disease, frequent or painful urination, scrotal 
mass in men and pelvic inflammatory disease in women as well as other symptoms, or 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 108 of 353
nonspecific symptoms. This is not an exhaustive list and unusual presentations should always be 
considered.
12.8.1.4.1
TB signs and symptoms questionnaire
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will assist with the identification of subjects who may
require therapy for TB. A subject who answers “Yes” to the question 
 at Screening is excluded. A “Yes” response to any of the other questions within the 
questionnaire at Screening should trigger further careful assessment to determine if subject has 
latent or active TB (see Section 6.2.2 (Exclusion Criterion #25). A “Yes” response to any of the 
questions during/end of the study should trigger further assessments as per local medical 
guidelines to determine if the subject has either LTB or active TB infection.
12.8.1.4.2
LTB infection, active TB or other NTMBI identified during study
During the study, subjects who develop evidence of LTB infection or active TB or NTMBI must
immediately stop further administration of study drug and will be referred to an appropriate 
medical specialist for further evaluation.
Confirmed LTB or active TB or NTMBI must be reported to the Sponsor immediately as 
described above.
12.8.2
Pregnancy testing
Pregnancy testing will consist of serum testing at Screening Visit and urine testing at dosing 
visits and End-of-Study Visit as indicated in the schedule of study assessments (Section 5.2). The 
Screening Visit serum pregnancy testing results must be negative and should be confirmed by a 
negative urine pregnancy test prior to first dose of IMP. The urine pregnancy test will be 
performed locally. A negative urine pregnancy test result should be obtained prior to each dose 
of IMP. A positive urine pregnancy test must be confirmed using a serum pregnancy test. 
Pregnancy tests should be administered to all female subjects of childbearing potential, 
regardless of their use of birth control. 
12.8.3
Vital signs
Vital signs will be measured at all visits as indicated in the schedule of study assessments 
(Section 5.2).
Vital signs to be assessed are as follows:

Pulse rate

Systolic/diastolic blood pressure 

Temperature (oral preferred, ear or axillary allowed)

Respiratory rate
Subjects should be sitting for 5 minutes prior and during the collection of blood pressure, pulse 
rate, and respiration rate measurements. On dosing days, vital signs will be measured prior to 
IMP administration, every 15 minutes during the infusion, at the end of infusion, 2 hours after 
end of infusion, and 4 hours after end of infusion.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 109 of 353
At nondosing visits, vital signs need only be taken once during the visit. 
12.8.4
Body weight and height
Subject’s body weight will be determined at Screening and at the End-of-Study Visit. Height will 
be measured at Screening only.
12.8.5
Physical examination
Physical examination will be performed at visits as specified in the schedule of study
assessments (Section 5.2) and findings will be recorded in the eCRF. A complete physical 
examination will be performed at Screening and EOS/Early Withdrawal Visit. At all other visits 
(where physical examination is performed), an abbreviated physical examination will be 
conducted.
Clinically important abnormal changes in subsequent physical examinations will be recorded as 
AEs. Physical examinations must be documented in source documentation.
The following body systems will be examined as a part of the complete physical examination:

General appearance

Ear, nose, and throat

Eyes

Hair and skin

Respiratory

Cardiovascular

Gastrointestinal

Musculoskeletal

Hepatic

Neurological (including limb reflexes)

Mental status

Abbreviated Physical Examination

The following body systems will be examined as a part of the abbreviated physical 
examination:

General appearance

Ear, nose, and throat

Eyes

Skin

Respiratory

Gastrointestinal

Neurological (focused assessment of sensitivity and power)
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
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
Neurological examination for severe headache
A neurological assessment will be performed only for subjects who experience severe headaches. 
This assessment will include: 1) General appearance, including posture, motor activity and 
meningeal signs and, if indicated, following assessments to be done; 2) Cranial nerves 
examination; 3) Motor system examination, including muscle tone and power and sensory
system examination – light touch; 4) Reflexes, including deep tendon reflexes; 5) Coordination, 
gait (if possible) and; 6) Fundoscopy.
12.8.6
12-Lead ECG
A standard 12-lead ECG will be performed at visits as specified in the schedule of study
assessments (Section 5.2). Care should be taken to assure proper lead placement and quality 
ECG recordings. Subjects should rest in a supine position in a controlled, calm environment for 
at least 15 minutes prior to the recording and should be motionless during the recording. 
The ECG will be performed in triplicate prior to blood collection for assessment of laboratory
parameters. Three ECGs should be recorded in a time frame of 5 minutes with at least 1 minute 
difference, 1-2 minutes between the ECGs.
The ECGs will be read at the clinical study site by an appropriately qualified physician. The PR,
RR, QRS, QT, and corrected QT (QTc) intervals and heart rate will be recorded. All ECG 
readings from an individual subject should be read by the same reader, if possible. Findings will 
be recorded in the eCRF.
For the QTc, the following correction formula will be applied:
Fridericia’s correction: QTc = QT/RR0.33
13
STUDY MANAGEMENT AND ADMINISTRATION 
13.1
Adherence to protocol
The investigator should not deviate from the protocol. However, the investigator should take any
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB/IEC, or 
sponsor.
After implementation of such measure, the investigator must notify the CPM of the sponsor 
within 24 hours and follow any local regulatory requirements.
13.2
Monitoring
UCB (or designee) will monitor the study to meet the sponsor’s monitoring Standard Operating 
Procedures (SOPs), ICH-GCP guideline, and applicable regulatory requirements, and to ensure 
that study initiation, conduct, and closure are adequate. Monitoring of the study may be 
delegated by UCB to a CRO or a contract monitor.
The investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any
missing information. The investigator(s)/institution(s) will permit direct access to source 
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data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory
inspection(s).
The investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol 
requirements, applicable authorities’ regulations, and investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records.
13.2.1
Definition of source data 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies of CRFs are not considered acceptable source 
documents. 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, or quality of life 
questionnaires, for example. Source documents should be kept in a secure, limited access area.
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the investigator and become a permanent part of the subject’s source documents. The 
investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent.
Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee).
13.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 13.2.1.
13.3
Data handling
13.3.1
Case Report form completion
The study will be performed using electronic data capture (EDC). The investigator is responsible 
for prompt reporting of accurate, complete, and legible data in the eCRFs and in all required 
reports.
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change.
Corrections made after the investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the investigator.
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The investigator should maintain a list of personnel authorized to enter data into the eCRF.
Detailed instructions will be provided in the eCRF Completion Guidelines.
13.3.2
Database entry and reconciliation
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure consistency of 
the data. In the EDC system, the data are entered into the eCRFs once by the designated site 
personnel and are subsequently verified.
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
13.3.3
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment 
Log.
The investigator will keep a Subject Identification Code list. This list remains with the 
investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
13.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the sponsor or by the investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP and other material in accordance with UCB procedures for the study.
13.5
Archiving and data retention
The investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
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agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The investigator will contact 
UCB for authorization prior to the destruction of any study records or in the event of accidental 
loss or destruction of any study records. The investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the sponsor’s 
study master file.
13.6
Audit and inspection
The investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IRB/IEC SOPs, ICH-GCP, and applicable regulatory
requirements.
The investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the investigator will immediately
inform UCB (or designee).
13.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
investigator, institution, institution staff, or designees of the sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
14
STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP). Deviations from the SAP will be documented in the Clinical Study Report.
14.1
Definition of analysis sets
Enrolled Set (ES):
The ES will consist of all subjects who have given informed consent.
Safety Set (SS):
The SS will consist of all subjects who have received at least 1 infusion (full or partial infusion) 
of IMP and will be used for the demographics and analysis of safety data.
Full Analysis Set (FAS):
The FAS will consist of all subjects who have received at least 1 infusion (full infusion) of IMP
and, in addition, have a Baseline and at least 1 post-Baseline measurement for platelet count.
The analysis of the PD (excluding total IgG, and IgG subclasses), efficacy, and immunologic 
variables will be performed on the FAS. Selected outputs may be repeated for the PD Per
Protocol Set (PD-PPS). Further details will be provided in the SAP. 
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Per Protocol Set:
The PPS is a subset of the FAS, consisting of those subjects who had received all foreseen sc 
infusions, had a platelet count measurement during the Observation Period, and no important 
protocol deviations that may potentially affect the platelet count as confirmed during a 
pre-analysis review of the data prior to database lock. Protocol deviations may not necessarily
lead to total exclusion of a subject from the PPS but may lead to exclusion of specific data. 
Pharmacokinetic Per Protocol Set (PK-PPS):
The PK-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations potentially affecting the plasma concentration of UCB7665, as confirmed during a 
pre-analysis review of the data prior to database lock. Protocol deviations may not necessarily
lead to total exclusion of a subject from the PK-PPS but may lead to exclusion of specific data.
Pharmacodynamic Per Protocol Set (PD-PPS)
The PD-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations potentially affecting the serum concentration of total IgG, as confirmed during a 
pre-analysis review of the data prior to database lock. Protocol deviations may not necessarily
lead to total exclusion of a subject from the PD-PPS but may lead to exclusion of specific data.
The PD-PPS will be used for the analysis of the total IgG, and IgG subclasses. 
14.2
General statistical considerations
All analyses will be performed using SAS® version 9.2 or later (SAS Institute, Cary, NC, USA). 
Continuous variables will be summarized by visit (where applicable) with the statistics including 
the number of subjects (n), mean, standard deviation (SD), median, minimum, and maximum. 
Categorical variables will be summarized by visit (where applicable) with frequency counts and 
percentages. Analyses will be performed by dose arm, unless otherwise stated. In the event that 
the number of planned infusions in the dose arms are modified following review by the DMC, 
the data will be summarized based on the actual dose arms completing the study. For example, if 
the weekly 5x4mg/kg dose arm is modified such that some subjects receive only 4 infusions, 
then the data will be summarized separately for this new dose regimen.
Data listings containing all documented data and all calculated data will be generated.
Baseline will be the last non-missing data collected prior to the first dose of IMP, and 
measurement-specific Baseline values will be defined in the SAP.
14.3
Planned safety analyses
14.3.1
Analysis of the primary safety variable
All AEs will be coded using the Medical Dictionary for Regulatory Activities® (MedDRA®). 
The incidence of subjects with TEAEs will be determined and presented by dose arm and 
overall.
Only TEAEs will be included in the summary tables. As an additional analysis, the incidence of 
subjects with TEAEs will be determined and presented separately for the Dosing Period and the 
Observation Period by dose arm and overall.
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Adverse events starting before time of IMP administration or after 8 weeks after the final dose 
will be listed only.
14.3.2
Other safety analyses
The absolute and relative frequencies for subjects with a given TEAE with respect to the 
preferred term according to the latest available version of the MedDRA, as well as the absolute 
frequencies of the individual TEAEs that have occurred, will be determined within each system 
organ class. Additional tables will summarize TEAEs by maximum intensity and causal 
relationship with UCB7665, as judged by the investigator. Adverse events will be categorized by
severity according to the CTCAE version 4.03 grading. In case the CTCAE grading is not 
available, the intensity (mild/moderate/severe) will be utilized. For the purpose of the tabulations 
CTCAE grades will be aligned with the intensity classifications (mild/moderate/severe) to enable 
pooling of the AEs in the summaries. The TEAEs leading to discontinuation of IMP and 
treatment-emergent SAEs will also be summarized. The action taken, time of onset relative to 
dosing, and duration of each AE will be listed only.
For the continuous laboratory variables, the values and changes from Baseline will be 
summarized at each time point. For categorized values according to the reference range, shift 
tables from Baseline to each post-Baseline time point will be presented for selected variables to 
be defined in the SAP. Values outside the reference range will be flagged in the data listings. The 
number and percentage of subjects with markedly abnormal laboratory results (based on CTCAE 
grading) will be tabulated for each dose arm.
Normal versus abnormal findings with regard to the various ECG parameters and the overall 
ECG will be analyzed as required. The focus of the 12-lead ECG analysis will be the 
identification of outliers and of any trends for changes following administration of UCB7665 
with respect to QT/QTc. Descriptive statistics will be presented for ECG value and changes from 
Baseline over time based on the mean of the triplicate assessments at each time point.
Descriptive statistics will be reported for all vital sign measurements (including systolic and 
diastolic blood pressure, pulse rate, temperature, and respiratory rate). Measured values and 
changes from Baseline will be summarized by time point.
Physical examination findings and the results of any pregnancy testing will be presented in 
listings only.
Safety analyses will be presented by dose arm.
14.4
Planned efficacy and other analyses
14.4.1
Efficacy analyses
The main efficacy variable is the maximum increase from Baseline in platelet count during the 
study. The maximum increase from Baseline and maximum platelet count during the study will 
be summarized by dose arm.
In addition, all measurements of platelet count will be summarized by dose arm and time point 
using descriptive statistics (including changes from Baseline).
For dose arms with ≥10 subjects, a 1-sided t-test will be applied to assess if the average 
maximum increase from Baseline is greater than zero. In case the assumptions for the-t-test are 
not fulfilled, an alternative nonparametric method may be considered. Further details will be 
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Clinical Study Protocol
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provided in the SAP. The Response, Complete Response, and platelet count ≥50x109/L will be 
summarized (number of subjects and percentages) and presented with 90% 2-sided confidence 
intervals for the rate of responders at each time point and overall (across all time points). 
Response and Complete Response are defined in Section 4.2.2. The analysis will be repeated for 
the Clinical Response variables defined in Section 4.2.2.
Time to Response, time to Complete Response, time to platelet count ≥50x109/L, duration of 
Response, duration of Complete Response, duration of platelet count ≥50x109/L, and 
Baseline-corrected AUEC for platelet count will be calculated and summarized by dose arm. The 
time to first response will be analyzed using a log-rank test and displayed using Kaplan-Meier 
curves. The time to Response, time to Complete Response, and respective durations will be 
summarized by dose arm.
The results from the ITP bleeding scale will be summarized at each time point and will include
the grades for each of the 3 major domains: skin (S), visible mucosae (M), and organs (O). In 
addition the number and percentage of subjects with severe or clinically relevant bleeding and 
number and percentage of subjects with absence of bleeding will be summarized at each time 
point.
Results of the NFI-MS will be summarized at each time point, using summary scores where 
applicable. Changes from Baseline will be calculated and summarized.
Additional subgroup analyses may be performed as needed and further details will be provided in 
SAP regarding these analyses.
14.4.2
Pharmacokinetic analyses
Pharmacokinetic variables of UCB7665 (eg, like AUC, Cmax) cannot be derived, since blood 
sampling will be performed at 1 time point per visit only. Thus, PK is restricted to concentration 
data.
Individual concentrations of UCB7665 data will be summarized using the number of available 
observations, mean, median, SD, minimum, maximum, geometric mean, and geometric 
coefficient of variation (assuming log normally distributed data). Values below the lower limit of 
quantification (LLOQ) will be reported with a clear sign indicating that they were below the 
LLOQ. Descriptive statistics of concentrations will be calculated if at least two thirds of the 
individual data points are quantifiable (≥LLOQ). Individual concentrations of UCB7665 will 
also be displayed graphically.
Population PK analyses and PK/PD analyses may be conducted for the PD variables of interest. 
All such PK and PK/PD analyses will be described in a separate Data Analysis Plan; however,
results will not be reported in the Clinical Study Report.
14.4.3
Pharmacodynamic analyses
For all PD variables, descriptive statistics for the values and change from Baseline and/or 
percentage change from Baseline will be tabulated by time point. 
The PD variables will include ITP-specific autoantibodies
total IgG, and IgG subclasses. In addition, for total IgG, the maximum decrease from Baseline 
and minimum value will be evaluated and summarized. Figures of mean values over time and 
changes from Baseline will be presented.
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Clinical Study Protocol
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14.4.4
Immunologic variables
All immunologic variables including concentrations of immunoglobulins (IgA, IgE, and IgM),
serum (C3 and C4) and plasma (C3a and C5a) complement levels, serum BAFF levels, and 
lymphocyte counts (B and T) will be summarized by dose arm over time (including changes 
from Baseline) using descriptive statistics. Figures of mean values over time and changes from 
Baseline may be presented.
The ADA status (negative/positive) will be summarized by dose arm at each visit and overall; 
figures will also be presented in conjunction with PK concentrations of UCB7665.
The results of any cytokine analyses (for subjects who experience infusion reactions) will be 
summarized if appropriate.
Further details will be provided in the SAP.
14.4.5
Other analyses
14.4.5.1
Subject disposition
The number of subjects who were screened, dosed and completed/prematurely discontinued the 
study, as well as the reason for discontinuation, will be presented using frequency counts and 
percentages.
14.4.5.2
Subject characteristics
Summaries of the following will be provided:

Demographics (including gender, age, height, weight, body mass index)

Medical history

Past, prior, and concomitant medications
Concomitant medical procedures will be listed only.
14.4.5.3
Baseline disease characteristics
Summaries of the following will be provided:

Baseline disease characteristics (including disease duration) 

Baseline values of the immunological parameters (IgG, IgM, IgA, IgE, lymphocytes 
[B and T])

ITP-specific antibodies

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)
14.4.5.4
Subject exit interview
The results of the exit interview will be reported by UCB and separate to the Clinical Study
Report.
14.5
Handling of protocol deviations
Important protocol deviations are identified as part of the data cleaning process in the Data 
Cleaning Plan (DCP). Ongoing data cleaning meetings will be held throughout the duration of 
the study. Objectives of these meetings include to review and update (if necessary) the important 
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protocol deviations in the DCP and discuss exclusion of subjects from analysis populations. 
Furthermore, overall trends in protocol deviations will be discussed at the Data Evaluation 
Meeting. Through this ongoing data cleaning and evaluation process, all decisions regarding 
important protocol deviations and exclusions from analysis populations are made on an ongoing 
basis.
14.6
Handling of dropouts or missing data
All imputation of missing or partial dates for safety assessments, as well as handling missing 
efficacy data (where applicable), will be detailed in the SAP.
14.7
Planned interim analysis and data monitoring
A DMC will be convened to monitor emergent safety data during the study. The DMC will 
comprise at least 1 external expert, the UCB study physician, the UCB PS representative, and a 
biostatistician. Safety related decisions must be made with the agreement of at least the external 
expert, the UCB study physician, and the UCB PS representative. Decisions involving reductions 
in dose regimen must also have the agreement of the UCB statistician and UCB 
pharmacometrician.
For the sequential adaptive design in this study, at least 11 interim analyses will be performed. 
Safety data from the interim analyses will be reviewed by the DMC to monitor the safety, to 
adapt the dose regimen, and to decide when and if the UCB7665 7mg/kg weekly group (Dose 
Arm 2), UCB7665 10mg/kg weekly group (Dose Arm 3), UCB7665 15mg/kg group (Dose 
Arm 4) and UCB7665 20mg/kg group (Dose Arm 5) should be opened. Planned dosing may be 
discontinued for all subjects in a dose arm (see Section 6.5).
The first interim analysis will be conducted after 3 subjects (receiving 5x4mg/kg) have attended 
the second visit of the Observation Period (ie, 7 days after final dosing). Based on this analysis,
the safety of UCB7665 will be assessed by the DMC. The DMC can either recommend to 
continue the study as planned, to reduce the number of sc infusions (eg, to 3), or to stop the 
study. If the number of infusions will be reduced, the subjects in the study already treated with 
the IMP will receive the reduced number of infusions. Subjects enrolled after the decision of the 
DMC will receive the reduced number of infusions. There will be no substitution of the subject 
with the original number of infusions; thus, the total number of subjects will not be increased. 
If the study continues without modifications, the next interim analysis will take place after data 
from 3 additional subjects are available. Based on the available combined data of the first 
6 subjects, the DMC will decide if the 3x7mg/kg dose arm can be initiated. If the new dose arm 
will be initiated and if the 5x4mg/kg will be continued, new subjects will be randomly assigned
to 1 of the 2 dose arms in an allocation ratio of 1:1.
If the decision is to open the 3x7mg/kg dose arm, the third interim analysis will be performed 
after 3 subjects (receiving 3x7mg/kg) have attended the second visit of the Observation Period 
(ie, 7 days after final dosing). The safety of UCB7665 will be assessed by the DMC. In addition, 
the DMC might recommend reducing the number of sc infusions in the UCB7665 7mg/kg dose 
arm. 
The fourth planned interim analysis and review of data by DMC will take place after safety data 
(7 days after final dose) is available for the first 6 subjects in Dose Arm 2.
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UCB
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Page 119 of 353
All subsequent DMC meetings will be dependent on opening of Dose Arms 3, 4 and 5 and 
decisions of the previous DMC meetings. Review of data will occur after every 3 subjects. More 
details are included in the DMC charter.
During the first three interim analyses, recruitment in the Dose Arms 1 and 2 will not be stopped. 
If needed, subsequent DMC meetings may take place and the frequency will be detailed in the 
DMC charter.
The DMC will monitor data for all reported AEs, clinical findings, including vital signs (pulse 
rate, blood pressure, temperature, and respiratory rate) and safety laboratory values, and 
immunogenicity data. Pharmacokinetic data will not be required for DMC review as blood 
sampling will be performed at a single time point per visit only. Thus, PK data are restricted only
to the concentration data and can therefore make no plausible contribution to the assessment of 
safety in this particular study.
Ad hoc DMC meetings can be held for other reasons if determined appropriate by the sponsor 
and/or external expert.
The deliberations and decisions of the DMC will be formally minuted/documented.
A detailed description of the DMC composition, processes and responsibilities, criteria to 
escalate to the next dose arm, and criteria to stop, or continue a dose arm will be provided in a 
separate DMC charter.
The analyses will be described in a separate interim SAP and will include all safety data 
specified in the DMC charter, which is available at the time. For the interim analyses the data, 
subject to analysis, should be as clean as possible; however, the database will not be locked and a 
snapshot will be taken.
14.8
Determination of sample size
The sample size of 15 subjects in Dose Arms 1 and 2, is mainly based on the efficacy objective 
of the study. In addition the 15 subjects in Dose Arms 1 and 2 ensure that sufficient data are 
available to form conclusions about the safety of administering UCB7665. Based on the safety
data from dose arms 1 and 2, the sample size of 6 to 12 subjects in Dose Arms 3, 4 and 5 is 
judged to be sufficient in order to explore subjects’ safety and IgG reductions under different 
dose regimens and is not based on a formal sample size calculation. 
For Dose Arms 1 and 2, an approximate sample size calculation for the efficacy variable 
“maximum increase from Baseline in platelet count” shows that 15 subjects would be sufficient 
to show a change from Baseline with 1-sided testing at 5% and power of 80%. The anticipated 
change is based on an assumed Baseline average of 25x109/L and a clinically meaningful 
maximum value of 100x109/L. The calculation made use of platelet count data presented in a 
publication by Robak T (Robak et al, 2009), but it is approximate as maximum changes from 
Baseline for individual subjects were not available, necessitating the use of the maximum 
average platelet count instead. The SD is taken from visual inspection.
With 15 subjects, the responder endpoints will confirm a true 50% response rate, in excess of the 
maximum 15% anticipated with no treatment benefit, with power in excess of 80%.
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15
ETHICS AND REGULATORY REQUIREMENTS
15.1
Informed consent
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the subject in both oral and written form by the investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the investigator.
Prior to participation in the study, the written Informed Consent form should be signed and 
personally dated by the subject, or his/her legal representative, and by the person who conducted 
the informed consent discussion (investigator or designee). The subject or his/her legal 
representative must receive a copy of the signed and dated Informed Consent form. As part of 
the consent process, each subject must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IRB/IEC review, and regulatory inspection.
If the Informed Consent form is amended during the study, the investigator (or the sponsor, if 
applicable) must follow all applicable regulatory requirements pertaining to the approval of the 
amended Informed Consent form by the IRB/IEC and use of the amended form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the Informed Consent form. An eCRF 
must not be started, nor may any study specific procedure be performed for a given subject, 
without having obtained his/her written consent to participate in the study.
Subjects have the right to withdraw their consent for the exploratory genomic substudy at any 
point without any impact on their care or participation in the main study. In this case, any data 
already generated on the samples will be retained and used, but no further analysis will occur.
15.2
Subject identification cards
Upon signing the Informed Consent and Assent form (as applicable), the subject or legal 
representative will be provided with a subject identification card in the language of the subject. 
The investigator will fill in the subject identifying information and medical emergency contact 
information. The investigator will instruct the subject to keep the card with him/her at all times.
15.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
The investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the investigator/UCB will forward copies of the protocol, Informed 
Consent form, Investigator’s Brochure, investigator’s curriculum vitae (if applicable), 
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advertisement (if applicable), and all other subject-related documents to be used for the study to 
the IRB/IEC for its review and approval.
Before initiating a study, the investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
The investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. For 
minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the investigator to obtain an expedited review by the IRB/IEC as 
allowed.
As part of the IRB/IEC requirements for continuing review of approved studies, the investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. The investigator should provide a final report to the IRB/IEC following study
completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory
authorities and all active investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the investigator or the sponsor, as specified by 
the applicable regulatory requirements in each concerned country. Where applicable, 
investigators are to provide the sponsor (or its representative) with evidence of such IRB/IEC 
notification.
15.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
assigned at Screening.
The investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
subject’s primary medical records that directly concerns this study (including, but not limited to, 
laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study).
Genetic analysis data will not be shared with the subjects and will be subject to the highest level 
of data protection, as per European regulations.
Samples may be shared with collaborators working within UCB and may be analyzed at a third 
party site, but only in relation to the aims of this exploratory analysis as detailed in this study
protocol. Samples may be stored for up to 20 years and maybe used at any time up to that point. 
Samples will remain under the control of UCB at all times and may be destroyed at any point 
before the 20 year expiration date.
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15.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
16
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the investigator and/or CRO 
agreements, as applicable.
17
REFERENCES
Anderson CL, Chaudhury C, Kim J, Bronson CL, Wani MA, Mohanty S. Perspective - FcRn 
transports albumin: relevance to immunology and medicine. Trends Immunol. 2006;27(7):343-8.
CPMP/ICH/135/95. Note for guidance on Good Clinical Practice (EMEA) Jul 2002.
EMA/CHMP/153191/2013. Guideline on the clinical development of medicinal products 
intended for the treatment of chronic primary immune thrombocytopenia Sep 2014.
Food and Drug Administration. Guidance for Industry. Drug-induced liver injury: premarketing 
clinical evaluation. US Dept of Health and Human Services, Center for Drug Evaluation and 
Research, Center for Biologics Evaluation and Research, 07/2009.
Ghanima W, Godeau B, Cines DB, Bussel JB. How I treat immune thrombocytopenia: the choice 
between splenectomy or a medical therapy as a second-line treatment. Blood. 2012;120(5):960-9.
Johnsen J. Pathogenesis in immune thrombocytopenia: new insights. Hematology Am Soc 
Hematol Educ Program. 2012;2012:306-12.
Lowe PJ, Tannenbaum S, Wu K, Lloyd P, Sims J. On setting the first dose in man: quantitating 
biotherapeutic drug-target binding through pharmacokinetic and pharmacodynamic models.
Basic Clin Pharmacol Toxicol. 2010;106(3):195-209. 
Mills RJ, Calabresi M, Tennant A, Young CA. Perceived changes and minimum clinically
important difference of the Neurological Fatigue Index for multiple sclerosis (NFI-MS). Mult
Scler. 2013;19:502-5.
Mills RJ, Young CA, Pallant JF, Tennant A. Development of a patient reported outcome scale 
for fatigue in multiple sclerosis: The Neurological Fatigue Index (NFI-MS). Health Qual Life 
Outcomes. 2010;8:22.
Robak T, Salama A, Kovaleva L, Vyhovska Y, Davies SV, Mazzucconi MG, et al. Efficacy and 
safety of Privigen®, a novel liquid intravenous immunoglobulin formulation, in adolescent and 
adult patients with chronic immune thrombocytopenic purpura. Hematology. 2009;14(4):227-36.
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arketing authorization application and any extensions or variations thereof.
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ice (EM
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ice (EM
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iza
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el JB. H
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Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, et al. 
Standardization of bleeding assessment in immune thrombocytopenia: report from the 
International Working Group. Blood. 2013;121(14):2596-606.
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization 
of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults 
and children: report from an international working group. Blood. 2009;113(11):2386-93.
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: summary report - Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. J Allergy Clin Immunol. 2006;117(2):391-7.
Sandler SG. The spleen and splenectomy in immune (idiopathic) thrombocytopenic purpura. 
Semin Hematol. 2000;37(1 Suppl 1):10-2.
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18.7
Protocol Amendment 1
Rationale for the amendment
The primary purpose of this substantial amendment it to include additional laboratory tests 
(serology test) at the Screening Visit in order to exclude subjects with chronic and ongoing 
infections with HIV, hepatitis B, and hepatitis C. Exclusion criteria related to medical history
were updated to define precisely and increase clarity. Withdrawal criteria for PDILI and 
evaluation of PDILI were also updated to enable the effective management and assessment of 
any PDILI cases as outlined in the Food and Drug Administration (FDA) Guidance for Industry, 
Drug-Induced Liver Injury: Premarketing Clinical Evaluation (Jul 2009), UCB has developed 
pre-specified criteria for managing any PDILI events and discontinuing IMP. In this amendment, 
a more conservative approach compared to the previous version is included. However, there have 
been no changes in the potential risk of PDILI with UCB7665 since the previous version. 
In addition, height was added in order to be able to calculate body mass index, the SAE reporting 
details were updated, and several additional exploratory biomarkers were added as 
immunological variables. Minor clarifications were added where necessary, and typographical 
errors or omissions were corrected.
Modifications and changes
Global changes
The following changes were made throughout the protocol:

Addition of HIV, hepatitis B, and hepatitis C test at the screening tests.

Addition of exploratory biomarker assessments.

Definition of complement levels for C3, C3a, C4 and C5a.
Specific changes
Change #1.
STUDY CONTACT INFORMATION
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Straße 10
40789 Monheim 
Germany
Phone:
Fax:
Has been changed to:
Name:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 144 of 353
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Straße 10
40789 Monheim 
GERMANY
Phone:
(mobile)
Fax:
Change #2.
STUDY CONTACT INFORMATION
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
Email
Global: DSICT@ucb.com (for interventional clinical studies)
Has been changed to:
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 65 61
Email
Global: safetyreportingUCB7665@ucb.com (for interventional 
clinical studies)
Change #3.
Section 1 SUMMARY
Paragraph 7
The first 6 subjects will be enrolled in Dose Arm 1 only. While recruitment is ongoing, safety
data for the first 3 subjects up to 7 days after the final dose will be reviewed by a Data 
Monitoring Committee (DMC). During a second DMC meeting, safety data for the first 6 
subjects up to 7 days after the final dose will be reviewed. Following this review, the DMC will 
make a decision on whether to open Dose Arm 2 for enrollment. Once the DMC has approved 
initiation of Dose Arm 2, subsequent subjects will be randomized to 1 of the 2 dose arms using 
an interactive voice/web response system (IXRS). The aim is to have 15 subjects in each dose 
arm. The DMC may also decide to reduce the number of doses in each of the dose arms based on 
review of data during the study. Safety data will also be reviewed on an ongoing basis during the 
study so as to continuously evaluate the safety of subjects.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 145 of 353
Has been changed to:
The first 6 subjects will be enrolled in Dose Arm 1 only. While recruitment is ongoing, safety
data for the first 3 subjects up to 7 days after the final dose of the third subject will be reviewed 
by the Data Monitoring Committee (DMC). During a second DMC meeting, all available safety 
data up to cut off date defined as 7 days after the final dose of the sixth subject will be reviewed.
Following this review, the DMC will make a decision on whether to open Dose Arm 2 for 
enrollment. Once the DMC has approved initiation of Dose Arm 2, subsequent subjects will be 
randomized to 1 of the 2 dose arms using an interactive voice/web response system (IXRS). 
Once 15 subjects are in the 4mg/kg group, the remaining subjects will not be randomized. They
will be allocated to the 7mg/kg group. The aim is to have 15 subjects in each dose arm. The 
DMC may also decide to reduce the number of doses in each of the dose arms based on review 
of data during the study. Safety data will also be reviewed on an ongoing basis during the study
so as to continuously evaluate the safety of subjects.
Change #4.
Section 1 SUMMARY
Paragraph 9
The secondary objective of the study is to assess the clinical efficacy of UCB7665 as measured 
by the change in platelet count and to assess the pharmacodynamic (PD) effect of UCB7665 as 
measured by the change in total IgG concentrations in blood. The exploratory objectives
; to evaluate the clinical efficacy as measured by 
the change in ITP bleeding score; to evaluate the effect of UCB7665 on the concentrations of 
total protein, albumin, α-globulin and β-globulin, IgG subclasses, IgM, IgA, and IgE, and serum 
complement levels; to evaluate the emergence of anti-drug antibodies (ADA), ie, anti-UCB7665 
antibodies with respect to immunogenicity and pharmacokinetics (PK)/PD; to evaluate the 
relationship between changes in platelet count and total IgG, IgG subclasses, ITP-specific 
autoantibodies; and to assess the plasma concentrations of UCB7665 administered by sc 
infusion.
Has been changed to:
The secondary objective of the study is to assess the clinical efficacy of UCB7665 as measured 
by the change in platelet count and to assess the pharmacodynamic (PD) effect of UCB7665 as 
measured by the change in total IgG concentrations in serum. The exploratory objectives include 
the following:
 to evaluate the clinical efficacy as measured by 
the change in ITP bleeding score; to evaluate the effect of UCB7665 on the concentrations of 
total protein, albumin, α-globulin and β-globulin, IgG subclasses, IgM, IgA, and IgE, and serum
or plasma complement levels; to evaluate the emergence of anti-drug antibodies (ADA), ie, 
anti-UCB7665 antibodies with respect to immunogenicity and pharmacokinetics (PK)/PD; to 
evaluate the relationship between changes in platelet count and total IgG, IgG subclasses, ITP-
specific autoantibodies; and to assess the plasma concentrations of UCB7665 administered by sc 
infusion.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 146 of 353
Change #5.
Section 1 SUMMARY
Paragraph 11
Description of PDILI evaluation has been added.
Change #6.
Section 1 SUMMARY
Paragraph 12
….. The PD variables are maximum change in total IgG concentration during the study; IgG 
subclass concentrations; and ITP-specific autoantibody
concentrations in blood over time. Other immunological variables to be evaluated are total IgA, 
IgE, and IgM levels; serum complement levels (C3, C3a, C4, and C5a); ADA; and cytokines (for 
subjects experiencing infusion reactions).
Has been changed to:
….. The PD variables are minimum value and maximum decrease in total IgG concentration 
during the study; IgG subclass concentrations; and ITP-specific autoantibody
in serum over time. Other immunological variables to be evaluated are 
total IgA, IgE, and IgM levels; serum (C3 and C4) and plasma (C3a and C5a) complement 
levels; ADA status (negative/positive) and relative mass units; serum biomarkers 
 B cell activating factor (BAFF) levels and the results of the 
IgG depletion assay; and cytokines (for subjects experiencing infusion reactions). Additional 
exploratory biomarkers may be investigated if needed using the samples already available.
Change #7.
Section 3.2
Secondary objectives
Bullet 2
The secondary objectives of this study are:

To assess the PD effect of UCB7665 as measured by the change in total IgG concentration in 
blood
Has been changed to:
The secondary objectives of this study are:

To assess the PD effect of UCB7665 as measured by the change in total IgG concentration in 
serum
Change #8.
Section 3.3
Exploratory objectives
Bullet 1 and 3
The exploratory objectives of this study are:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 147 of 353


To evaluate the effect of UCB7665 on the concentrations of total protein, albumin, 
α-globulin and β-globulin, IgG subclasses, IgM, IgA, and IgE, and serum complement levels
Has been changed to:
The exploratory objectives of this study are:


To evaluate the effect of UCB7665 on the concentrations of total protein, albumin, 
α-globulin and β-globulin, IgG subclasses, IgM, IgA, and IgE, and serum or plasma 
complement levels
Change #9.
Section 4.2
Efficacy variables
Bullet 15

Value and change from Baseline in the ITP bleeding score over time
Has been changed to:

ITP bleeding score over time
Change #10.
Section 4.3.2 Pharmacodynamic variables
The PD variables are:

Maximum change from Baseline in total IgG concentration during the study

Change from Baseline in ITP-specific autoantibody concentrations in blood over time: 

Change from Baseline in IgG subclass concentrations over time

Value and change from Baseline in IgG concentrations over time
Has been changed to:

Minimum value and maximum decrease from Baseline in total IgG concentration during the 
study

Value and change from Baseline in total IgG concentrations over time

The value and change from Baseline in endogenous IgG concentrations will be measured by 
IgG depletion assay

Change from Baseline in ITP-specific autoantibody in serum over time: 

Change from Baseline in IgG subclass concentrations over time
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 148 of 353
Change #11.
Section 4.4
Other immunological variables
Other immunological variables are:

Change from Baseline in immunoglobulin concentrations (total IgA, IgE, and IgM) over time

Change from Baseline in serum complement levels (C3, C3a, C4, and C5a) over time

Value and change from Baseline in ADA (anti-UCB7665 antibodies) over time

Cytokines
Cytokine samples will be taken at Baseline for all subjects and at subsequent visits only if the 
subject experiences infusion reactions.
Has been changed to:
Other immunological variables are:

Change from Baseline in serum immunoglobulin concentrations (total IgA, IgE, and IgM) 
over time

Change from Baseline in serum (C3 and C4) and plasma (C3a and C5a) complement levels 
over time

Change from Baseline in serum biomarkers 
over time

ADA (anti-UCB7665 antibodies) status (negative/positive) and change from Baseline in
relative mass units over time

Change from Baseline in cytokines over time (for subjects experiencing infusion reactions)

Change from Baseline in serum BAFF levels over time
Cytokine samples will be taken at Baseline for all subjects and at subsequent visits only if the 
subject experiences infusion reactions. 
Additional exploratory biomarkers may be investigated if needed using the samples already
available.
Change #12.
Section 5.1
Study description
Paragraph 5
Dosing Period: The first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in 
the Dose Arm 1 will not be randomized. While recruitment is still ongoing, safety data for the 
first 3 subjects up to 7 days after the final dose will be reviewed by a DMC. During a second 
DMC meeting, safety data for the first 6 subjects up to 7 days after the final dose will be 
reviewed. During these reviews recruitment in the dose arm will not be stopped. Following this 
review, the DMC will make a decision on whether to open Dose Arm 2 for enrollment. Once the 
DMC has approved opening of Dose Arm 2 for enrollment, subjects will subsequently be 
randomized to one of the 2 dose arms using IXRS. If the new dose arm will be initiated and if the 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 149 of 353
UCB7665 4mg/kg arm will be continued, new subjects will be randomized to 1 of the 2 dose 
arms in an allocation ratio of 1:1 (randomization will stop once 15 subjects are treated with 
UCB7665 4mg/kg dose).
Has been changed to:
Dosing Period: The first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in 
the Dose Arm 1 will not be randomized. While recruitment is still ongoing, safety data for the 
first 3 subjects up to 7 days after the final dose of the third subject will be reviewed by the DMC. 
During a second DMC meeting, all available safety data up to cut off date defined as 7 days after 
the final dose of the sixth subject will be reviewed. During these reviews recruitment in the dose 
arm will not be stopped. Following this review, the DMC will make a decision on whether to 
open Dose Arm 2 for enrollment. Once the DMC has approved opening of Dose Arm 2 for 
enrollment, subjects will subsequently be randomized to 1 of the 2 dose arms using IXRS. If the 
new dose arm will be initiated and if the UCB7665 4mg/kg arm will be continued, new subjects 
will be randomized to 1 of the 2 dose arms in an allocation ratio of 1:1 (Once 15 subjects are in 
the 4mg/kg group, the remaining subjects will not be randomized. They will be allocated to the 
7mg/kg group.).
Change #13.
Section 5.2
Schedule of study assessments
Assessments of height, serology test for HIV, hepatitis B, and hepatitis C and biomarkers have 
been added to the Table 5-1. Footnotes f, g, n have been updated.
Change #14.
Section 5.2
Schedule of study assessments
Assessments of height, serology test for HIV, hepatitis B, and hepatitis C and biomarkers have 
been added to the Table 5-2. Footnotes f, g, n have been updated.
Change #15.
Section 5.2
Schedule of study assessments
Assessments of biomarkers have been added to the Table 5-3. Footnote d has been updated.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 150 of 353
Table 5-1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consent
X
Demographic data
X
Verification of 
inclusion/exclusion 
criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)f
X
X
X
X
X
Randomizationg
X
Withdrawal criteriah
X
X
X
X
X
X
General 
medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 151 of 353
Table 5-1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
X
X 
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis 
C
X
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 152 of 353
Table 5-1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
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±2dd
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±1d
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±2de
Blood sample for 
cytokines
X
Xk
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
X
X
Call to IXRS for treatment 
kit number
X
X
X
X
X
Administration of IMP
X
X
X
X
X
Blood sampling for 
plasma concentration of 
UCB7665
X
X
X
X
X
X
X
X
Anti-UCB7665 
antibodies/IgG depletion 
assay
X
X
X
X
X
X
X
X
X
X
X
X
Serum complements (C3 
and C4) and plasma 
complements (C3a and 
C5a)
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 153 of 353
Table 5-1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serum biomarkers 
 
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum biomarkers 
X
X
X
X
X
X
Serum BAFF levels
X
X
X
X
X
X
X
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
IgA, IgM, IgEl
X
X
X
X
ITP-specific 
autoantibodiesm
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairen
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewo
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 154 of 353
AE=adverse event; BAFF= B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
; HIV=human immunodeficiency virus;
Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar 
puncture; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
a Frequency of assessments on dosing days is detailed in Table 5-3.  
b Visits 10, 12, and 14 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date.
g Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h The first 6 subjects will be enrolled in the Dose Arm 1 group only. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the
DMC. Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, subjects subsequently enrolled will 
be randomly assigned subsequently to 1 of the 2 dose arms using an IXRS until 15 subjects are in Dose Arm 1.
Error! Reference source not found.
Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
Error! Reference source not found.
A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical 
examination is performed), an abbreviated physical examination will be conducted.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
n Blood sample for cytokines will be obtained only in case of infusion reactions.
Error! Reference source not found.
In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 
7 assessment for IgA, IgM, and IgE will be performed earlier at the last dosing visit.
Error! Reference source not found.
Error! Reference source not found.
This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution 
(ie, if headache becomes moderate or mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including
fundoscopy). Additionally, other diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at 
the discretion of the investigator, considering the local guidelines for performing LP in subjects with ITP.
Error! Reference source not found.
A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the 
study, the subject exit interview should be performed at End-of-Study Visit only. 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 155 of 353
Table 5-2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consent
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
X
Platelets for inclusion/withdrawal 
check (local laboratory) f
X
X
X
Randomizationg
X
Withdrawal criteriah
X
X
X
X
General medical/procedures history
X
ITP history
X
Prior and concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 156 of 353
Table 5-2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Physical examinationi
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters (hematology, 
chemistry, urinalysis)
Xj
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, hepatitis B, and 
hepatitis C
X
Blood sample for cytokines
X
Xk
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
Call to IXRS for treatment kit number
X
X
X
Administration of IMP
X
X
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
X
X
X
Anti-UCB7665 antibodies/IgG 
depletion assay
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 157 of 353
Table 5-2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serum complements (C3 and C4) and 
plasma complements (C3a and C5a)
X
X
X
X
Serum biomarkers 
 
X
X
X
X
X
X
X
X
X
X
X
Serum biomarkers 
X
X
X
X
Serum BAFF levels
X
X
X
X
X
Immunoglobulins (total IgG, IgG 
subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEl
X
X
X
X
ITP-specific autoantibodiesm
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairen
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewo
X
AE=adverse event; BAFF=B cell activating factor; BL=baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human immunodeficiency virus;
Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar 
REDACTED COPY
X
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X
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C
 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 158 of 353
puncture; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
a Frequency of assessments on dosing days is detailed in Table 5‒3.
b Visits 8, 10, and 12 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date. 
(local laboratory)Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion 
criteria. The other platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to 
evaluate withdrawal criterion of platelet count >350x109/L.
h The first 6 subjects will be enrolled in the Dose Arm 1 group. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the DMC. 
Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, subjects subsequently enrolled will be 
randomly assigned to one of the dose arms using an IXRS until 15 subjects are in Dose Arm 1.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
n Blood sample for cytokines will be obtained only in case of infusion reactions.
Error! Reference source not found.
In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 
5 assessment for IgA, IgM, and IgE will be performed earlier at the last dosing visit.
Error! Reference source not found.
Error! Reference source not found.
This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution 
(ie, if headache becomes moderate or mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including 
fundoscopy). Additionally, other diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at 
the discretion of the investigator, considering the local guidelines for performing LP in subjects with ITP.
Error! Reference source not found.
A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the 
study, the subject exit interview should be performed at End-of-Study Visit only.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 159 of 353
Table 5-3:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of infusion
4h after end of infusion
Withdrawal criteria
X
Platelet count (local laboratory) for inclusion check 
at Visit 2 and for withdrawal criterion at other 
dosing visits
X
Prior and concomitant medications
X
Concomitant medical procedures
X
Vital signsa
X
X
X
X
Physical examination
X
12-lead ECG
X
Hematology 
X
Clinical chemistry
X
Urinalysis
X
Urine pregnancy test
X
Immunoglobulinsb
X
ITP-specific autoantibodiesc
X
Blood sampling for UCB7665 plasma 
concentration
X
Anti-UCB7665 antibodies/IgG depletion assay
X
Serum (C3 and C4) and plasma complements (C3a 
and C5a)d
X
Serum biomarkers 
X
X
X
Serum BAFF levels
X
X
X
Blood sampling for cytokinese
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 160 of 353
Table 5-3:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of infusion
4h after end of infusion
ITP bleeding scale
X
AEs
X
X
X
X
NFI-MSf
X
AE=adverse event; BAFF=B cell activating factor; ECG=electrocardiogram; h=hours; Ig=immunoglobulin; IMP=investigational medicinal product; 
ITP=immune thrombocytopenia; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
 PRO=Patient Reported 
Outcomes; 
b In addition to time points mentioned, vital signs will be evaluated every 15 minutes during infusion. Respiratory rate will be assessed only once predose.
d Total IgG and IgG subclasses. 
e Evaluation of ITP-specific autoantibodies will be performed prior to dose 1 only. 
f Serum and plasma complement levels will be assessed prior to dose 1 and dose 3 only.
Error! Reference source not found.
Blood sample for Baseline cytokine values will be obtained at Visit 2 for all subjects at predose and at other visits in case 
of infusion reactions.
Error! Reference source not found.
PRO endpoint (NFI-MS) will be assessed prior to dose 1 only.
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This document cannot be used to support any marketing authorization a
obtained
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atio
or to do
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 161 of 353
Change #16.
Section 6.2.1 Exclusion criteria related to health status
Number 3 and 10
3. Subject has a Karnofsky Performance Status (Appendix 18.1) rating <60 at Screening Visit.
10. Subject has liver impairment, defined as:

Subject has >2xULN alanine aminotransferase (ALT) or alkaline phosphatase (ALP), or 
>ULN bilirubin (≥1.5xULN bilirubin if known Gilbert’s syndrome) at Screening Visit. If 
the subject has isolated >ULN and <1.5xULN bilirubin, fractionate bilirubin to identify
possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%).
For subjects with a Baseline result >ULN, a baseline diagnosis and/or the cause of any 
clinically meaningful elevation must be understood and recorded in the medical history
section of the electronic Case Report form (eCRF).
If subject has >ULN that does not meet the exclusion limit for ALT or ALP at screening, 
repeat, if possible, prior to dosing to ensure there is no further ongoing clinically relevant 
increase. In case of a clinically relevant increase, inclusion of the subject must be discussed 
with the Medical Monitor. 
Serum ALT results up to 25% above the upper exclusion limit may be repeated once for 
confirmation. This includes rescreening (see Section 6.3).
Has been changed to:
3. Subject has a Karnofsky Performance Status (Appendix 18.1) rating <60% at Screening Visit.
10. Subject has liver impairment, defined as:

Subject has >1.5xULN of any of the following: alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), or alkaline phosphatase (ALP), or >ULN total 
bilirubin (≥1.5xULN total bilirubin if known Gilbert’s syndrome). If the subject has 
elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to 
identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%).
For subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a Baseline 
diagnosis and/or the cause of any clinically meaningful elevation must be understood and 
recorded in the electronic Case Report form (eCRF).
If subject has >ULN for ALT, AST, or ALP that does not meet the exclusion limit at 
screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing 
clinically relevant increase. In case of a clinically relevant increase, inclusion of the subject 
must be discussed with the Medical Monitor. 
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes rescreening (see Section 6.3).
Change #17.
Section 6.2.2
Exclusion criteria related to medical history
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 162 of 353
14. Subject has evidence of a secondary cause of immune thrombocytopenic purpura from the 
past medical history (eg, bacterial or viral infection, past medical history of leukemia, 
lymphoma, combined variant immunodeficiency, systemic lupus erythematosus, thyroid 
disease) or to drug treatments (eg, heparin, quinine, antimicrobials, anticonvulsants) or 
subject has a multiple immune cytopenia, eg, Evan’s syndrome.
15. Subject has a history of clinically relevant ongoing chronic infections including but not 
limited to human immunodeficiency virus (HIV), hepatitis B, hepatitis C, active or latent 
tuberculosis.
20. Subject has a history of known inflammatory bowel disease, diverticular disease, and gastric 
or esophageal ulceration.
21. Subject has experienced gastrointestinal bleed in the last 6 months prior to Screening Visit 
and/or has current gastritis or esophagitis.
23. Subject has a medical history of thrombosis.
24. Subject has a history of coagulopathy disorders.
Has been changed to:
14. Subject has evidence of a secondary cause of immune thrombocytopenic purpura from the 
past medical history (eg, bacterial or viral infection, past medical history of leukemia, 
lymphoma, common variable immunodeficiency, systemic lupus erythematosus, 
auto-immune thyroid disease) or to drug treatments (eg, heparin, quinine, antimicrobials, 
anticonvulsants) or subject has a multiple immune cytopenia, eg, Evan’s syndrome.
15. Subject has a history of clinically relevant ongoing chronic infections including but not 
limited to human immunodeficiency virus (HIV), hepatitis B, hepatitis C, active or latent 
tuberculosis, or is tested positive for HIV, hepatitis B, or hepatitis C at the Screening Visit.
20. Subject has a history of known inflammatory bowel disease, diverticular disease, or has a 
history of confirmed, duodenal, gastric or esophageal ulceration in the past 6 months.
21. Subject has experienced a clinically symptomatic gastrointestinal bleed (positive hemoccult 
tests without any signs and symptoms of gastrointestinal bleedings will not be considered as 
“clinically symptomatic”) in the last 6 months prior to Screening Visit and/or has current 
gastritis or esophagitis and/or has a known risk for clincial relevant gastrointestinal bleeding 
beyond ITP.
23. Subject has a medical history of thrombosis within the past 5 years or a history of thrombosis 
with unknown cause at any time or a known significant risk for thrombosis.
24. Subject has a history of coagulopathy disorders other than ITP.
Change #18.
Section 6.2.3 Exclusion criteria related to concomitant medications/procedures
Definition of generic name was added and wording of “wash-out” changed to “washout” in 
Table 6-1.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 163 of 353
Table 6-1:
Washout periods for immunosuppressants, biologics and other 
therapies
Generic name (most common commercial/trade 
names)
Washout period relative to Baseline Visit 
(regardless of route)
Immunosuppressants
Cyclophosphamide 
6 months
Pimecrolimus (Elidel®)
4 weeks
Vinca alkaloids (vincristine, vinblastine)
12 weeks
Biologics (mAbs and fusion proteins)
Abatacept (CTLA 4-Ig) (Orencia®)
6 months
Belimumab (Benlysta™)
6 months
Golimumab (Simponi™)
6 months
Natalizumab (Tysabri®)
6 months
Ofatumumab (Arzerra)
6 months
Rituximab (Rituxan®) and ocrelizumab
6 months
TACI-Ig (Atacicept)
10 months
Veltuzumab
6 months
Other biologics
3 months
Others
Intravenous immunoglobulin
4 weeks
IPP-201101 (Lupuzor™)
3 months
Plasma exchange (PLEX)
4 weeks
TPO-R agonists (eltrombopag, romiplostim)
4 weeks
Anti-D
4 weeks
Antiplatelets and Anticoagulants (Vitamin K 
antagonists)
Warfarin
2 weeks
Fenprocoumon
2 weeks
Acenocoumarol
2 weeks
Heparin
1 week
Clopidogrel
1 week
Salicylates (Aspirin)
1 week
Dipyramidole
1 week
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 164 of 353
Table 6-1:
Washout periods for immunosuppressants, biologics and other 
therapies
Generic name (most common commercial/trade 
names)
Washout period relative to Baseline Visit 
(regardless of route)
Prasugrel
1 week
Ticagrelor
1 week
Tirofiban
1 week
Abciximab
1 week
Change #19.
Section 6.4
Withdrawal criteria
Number 2, bullet 5
2. Subject develops an illness or has a change in health status that would interfere with his/her 
continued participation, including but not limited to:

Subject has a clinically severe (life threatening) bleeding event (Skin [S]>2 and/or 
Mucosae [M]>1 and /or Organ [O]>1).
Has been changed to:
2. Subject develops an illness or has a change in health status that would interfere with his/her 
continued participation, including but not limited to:

Subject has a life threatening bleeding event.
Change #20.
Section 6.4
Withdrawal criteria
Subjects with potential drug-induced liver injury (PDILI) MUST stop treatment with IMP. In 
addition, all concomitant medications and herbal supplements that are not medically necessary
should also be stopped.
The below PDILI criteria require immediate and permanent discontinuation of IMP:

Subjects with any of the following:

ALT ≥8xULN

ALT ≥3xULN and co-existing total bilirubin ≥2xULN 
The below PDILI criteria requires immediate discontinuation of IMP:

Subjects with ALT ≥3xULN who exhibit a temporally associated fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever (without clear alternative cause), rash, or 
eosinophilia (ie, >5%) must be immediately discontinued from IMP.
If a nondrug related cause for the symptoms can be confirmed, these subjects may resume IMP 
administration after discussion with the Medical Monitor.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 165 of 353
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
investigator.

ALT ≥3xULN (and ≥2x Baseline) and <8xULN, total bilirubin <2xULN, and no eosinophilia 
(ie, ≤5%), with no fever, rash, or symptoms of hepatitis (eg, fatigue, nausea, vomiting, right 
upper quadrant pain, or tenderness).
The investigator must consult UCB Medical Monitor within 24 hours if ALT ≥3xULN (with or 
without increase in bilirubin or with/without symptoms of liver dysfunction) and further dosing 
should be withheld until after discussion with UCB medical monitor.
Has been changed to:
Subjects with PDILI must be assessed to determine if IMP must be discontinued. In addition, all 
concomitant medications and herbal supplements that are not medically necessary should also be 
discontinued.
The PDILI criteria below require immediate and permanent discontinuation of IMP:

Subjects with either of the following:

ALT or AST ≥5xULN

ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 
The PDILI criterion below requires immediate discontinuation of IMP:

Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).
If a nondrug-related cause for the symptoms can be confirmed, these subjects may resume IMP 
administration after discussion with responsible UCB physician, but only when the requirements 
for rechallenge with IMP as provided in Section 12.7.1.2.1 are followed.
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
investigator.

Subjects with ALT or AST ≥3xULN (and ≥2x Baseline) and <5xULN, total bilirubin 
<2xULN, and no eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis (eg, 
fatigue, nausea, vomiting, right upper quadrant pain, or tenderness).
Evaluation of PDILI must be initiated as described in Section 12.7.1. If subjects are unable to 
comply with the applicable monitoring schedule, IMP must be discontinued immediately.
Change #21.
Section 7.8.1 Permitted immunosuppressant medications
Dose unit for Cyclosporin was updated.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 166 of 353
Has been changed to:
Table 7‒1:
Permitted immunosuppressant medications
Permitted medications
Dose
Comment
Oral corticosteroids 
(prednisolone)
≤10mg/day
Stable dose for 2 weeks prior to Baseline
Methotrexate
≤30mg/week
Stable dose for 2 months prior to Baseline
Mycophenolate mofetil
≤3g/day
Stable dose for 2 months prior to Baseline
Cyclosporin
≤5mg/kg/day
Stable dose for 2 months prior to Baseline
Azathioprine
≤3mg/kg/day
Stable dose for 2 months prior to Baseline
Danazol
≤15mg/kg/day
Stable dose for 2 months prior to Baseline
Dapsone
100mg/day
Stable dose for 2 months prior to Baseline
Change #22.
Section 7.8.2
Prohibited concomitant treatments (medications and therapies)
Bullet 12 

Anticoagulants and antiplatelets (warfarin, heparin, clopidogrel, aspirin, salicylics, 
dipyramidole, prasugrel, ticregelor, ticofiban, abiximab)
Has been changed to:

Anticoagulants and antiplatelets (warfarin, heparin, clopidogrel, aspirin, salicylics, 
dipyramidole, prasugrel, tricagrelor, tirofiban, abciximab)
Change #23.
Section 7.10
Randomization and numbering of subjects
Paragraph 2
The first 6 subjects (and those treated before DMC assessment after the 6 subjects) will not be 
randomized. Once the DMC has approved opening of Dose Arm 2 for enrollment, subsequent 
subjects will be randomized to 1 of the 2 dose arms in a 1:1 ratio.
Has been changed to:
The first 6 subjects (and those treated before DMC assessment after the 6 subjects) will not be 
randomized. Once the DMC has approved opening of Dose Arm 2 for enrollment, subsequent 
subjects will be randomized to 1 of the 2 dose arms in a 1:1 ratio. Once 15 subjects are in the 
4mg/kg group, the remaining subjects will not be randomized. They will be allocated to the 
7mg/kg group.
Change #24.
Section 7.10
Randomization and numbering of subjects
Paragraph 4
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 167 of 353
To randomize a subject, the investigator or designee will contact the IXRS and provide brief 
details about the subject to be randomized. The IXRS will automatically inform the investigator 
or designee of the subject’s randomization number. The IXRS will allocate kit numbers to the 
subject based on the subject number during the course of the study.
Has been changed to:
To randomize a subject, the investigator or designee will contact the IXRS and provide brief 
details about the subject to be randomized. The IXRS will automatically inform the investigator 
or designee of the subject’s kit number. The IXRS will allocate kit numbers to the subject based 
on the subject number or randomization during the course of the study.
Change #25.
Section 8.1.1
Visit 1 (Day -28 to -1) Screening Visit
Following assessments have been added.

Height

Serology test for HIV, hepatitis B, and hepatitis C
Change #26.
Section 8.2.1
Visit 2 (Week 1/Day 1) Baseline Visit
Paragraphs 1, 2, 3 and 4
Visit 2 can occur at any time after Visit 1, but no later than 28 days after Visit 1. Prior to 
randomization, 2 platelet samples will be taken. One sample will be analyzed locally and the 
value will be used to check inclusion criterion. The other platelet sample will be sent to the 
central laboratory.
Eligible subjects will be randomized at Visit 2 and first dose of IMP will be administered as per 
the subject’s randomization, except that the first 6 subjects will be enrolled in Dose Arm 1.
Subjects randomized to Dose Arm 1 (UCB7665 4mg/kg sc) will receive a total of 5 doses of IMP 
at Visit 2 (Day 1, Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), and Visit 7 
(Week 5). 
Subjects randomized to Dose Arm 2 (UCB7665 7mg/kg sc) will receive a total of 3 doses of IMP 
at Visit 2 (Day 1, Week 1), Visit 4 (Week 2), and Visit 5 (Week 3).
Has been changed to:
Visit 2 can occur at any time after Visit 1, but no later than 28 days after Visit 1. Prior to dosing 
at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value 
will be used to check inclusion criterion. The other platelet sample will be sent to the central 
laboratory.
Eligible subjects will be treated with IMP at Visit 2. The first 6 subjects will be enrolled in Dose 
Arm 1, subsequent subjects will be randomized to 1 of the 2 dose arms. Once 15 subjects are in 
Dose Arm 1, the remaining subjects will not be randomized. They will be allocated to Dose 
Arm 2.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 168 of 353
Subjects allocated to Dose Arm 1 (UCB7665 4mg/kg sc) will receive a total of 5 doses of IMP at 
Visit 2 (Day 1, Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), and Visit 7 (Week 
5). 
Subjects allocated to Dose Arm 2 (UCB7665 7mg/kg sc) will receive a total of 3 doses of IMP at 
Visit 2 (Day 1, Week 1), Visit 4 (Week 2), and Visit 5 (Week 3). 
Change #27.
Section 8.2.1 Visit 2 (Week 1/Day 1) Baseline Visit
Definition of complement levels were updated as:

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)
And following assessments have been added:

Serum biomarkers 
 and
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF

Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to computed tomography (CT) scan, magnetic resonance imaging 
(MRI) and/or lumbar puncture (LP) for cerebrospinal fluid (CSF) collection to be performed 
if indicated at the discretion of the investigator, considering the local guidelines for 
performing LP in subjects with ITP. 
Change #28.
Section 8.2.2 Visit 3 (Week 1/Day 4)
Following assessments have been added:

Serum biomarkers 

Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP. 
Change #29.
Section 8.2.3 Visit 4 (Week 2/Day 8)
Following assessments have been added.

Call IXRS to obtain treatment kit number(s)

Blood sample for the following laboratory parameters:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 169 of 353

Serum biomarkers 
 and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #30.
Section 8.2.4
Visit 5 (Week 3/Day 15)
Definition of complement levels were updated as:

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)
Following assessments have been added.

Call IXRS to obtain treatment kit number(s)

Blood sample for the following laboratory parameters:

Serum biomarkers 
and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #31.
Section 8.2.5 Visit 6 (Week 4/Day 22) [UCB7665 4mg/kg only]
And following assessments have been added.

Call IXRS to obtain treatment kit number(s)

Blood sample for the following laboratory parameters:

Serum biomarkers 
 and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF

Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 170 of 353
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP. 
Change #32.
Section 8.2.6 Visit 7 (Week 5/Day 29) [UCB7665 4mg/kg only]
Following assessments have been added.

Call IXRS to obtain treatment kit number(s)

Blood sample for the following laboratory parameters:

Serum biomarkers 
and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF
Description for Headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #33.
Section 8.3.1 Visit 8 (Week 5/Day 32) [UCB7665 4mg/kg]/ Visit 6 (Week 3/Day 18) 
[UCB7665 7mg/kg]
Definition of complement levels were updated as:

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)
And following assessments have been added.

Serum biomarkers 

Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to computed tomography (CT) scan, magnetic resonance imaging 
(MRI) and/or lumbar puncture (LP) for cerebrospinal fluid (CSF) collection to be performed 
if indicated at the discretion of the investigator, considering the local guidelines for 
performing LP in subjects with ITP. 
Change #34.
Section 8.3.2 Visit 9 (Week 6/Day 36) [UCB7665 4mg/kg]/ Visit 7 (Week 4/Day 22) 
[UCB7665 7mg/kg]
Following assessments have been added.

Blood sample for the following laboratory parameters:

Serum biomarkers 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 171 of 353
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, otherdiagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #35.
Section 8.3.3 Visit 10 (Week 7/Day 43) [UCB7665 4mg/kg]/ Visit 8 (Week 5/Day 29) 
[UCB7665 7mg/kg] 
Following assessments have been added.

Blood sample for the following laboratory parameters:

Serum biomarkers 

Serum BAFF levels
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #36.
Section 8.3.4 Visit 11 (Week 8/Day 50) [UCB7665 4mg/kg]/ Visit 9 (Week 6/Day 36) 
[UCB7665 7mg/kg]
Following assessments have been added.

Blood sample for the following laboratory parameters:

Serum biomarkers 
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #37.
Section 8.3.5 Visit 12 (Week 9/Day 57) [UCB7665 4mg/kg]/ Visit 10 (Week 7/Day 43) 
[UCB7665 7mg/kg]
Definition of complement levels were updated as:

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 172 of 353
Following assessments have been added.

Blood sample for the following laboratory parameters:

Serum biomarkers 
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #38.
Section 8.3.6 Visit 13 (Week 10/Day 64) [UCB7665 4mg/kg]/ Visit 11 (Week 8/Day 50) 
[UCB7665 7mg/kg]
Following assessments have been added.

Blood sample for the following laboratory parameters:

Serum biomarkers 
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #39.
Section 8.3.7 Visit 14 (Week 11/Day 71) [UCB7665 4mg/kg]/ Visit 12 (Week 9/Day 57) 
[UCB7665 7mg/kg]
Following assessments have been added.

Blood sample for the following laboratory parameters:

Serum biomarkers 

Serum BAFF levels
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 173 of 353
Change #40.
Section 8.3.8 End-of-Study Visit: Visit 15 (Week 13/Day 85) [UCB7665 4mg/kg]/ Visit 13 
(Week 11/Day 71) [UCB7665 7mg/kg]
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #41.
Section 8.5
Unscheduled Visit
Description for headache questionnaire was updated as:

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/ or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Change #42.
Section 10.2
Pharmacodynamic variables
Bullet 3

ITP-specific autoantibody concentration
Has been changed to:

Serum ITP-specific autoantibody
Change #43.
Section 11 ASSESSMENT OF OTHER IMMUNOLOGICAL VARIABLES
For all immunological assessments, blood samples will be collected predose (at dosing visits) by
qualified site personnel at the same time that samples are collected for standard clinical 
laboratory. The time and date of the blood draws will be recorded in the eCRF. The following 
immunological assessments will be performed according to the schedule of study assessments 
(Section 5.2).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 174 of 353

Serum immunoglobulin concentration over time

IgA

IgE

IgM

Serum complement levels over time

C3

C3a

C4

C5a

Plasma anti-UCB7665 antibodies/IgG depletion assay 

Cytokines
Cytokine samples will be taken at Baseline Visit for all subjects. At subsequent visits, cytokine 
samples will be taken only when the subject experiences infusion reactions.
Has been changed to:
For all immunological assessments, blood samples will be collected predose (at dosing visits) by
qualified site personnel at the same time that samples are collected for standard clinical 
laboratory. The time and date of the blood draws will be recorded in the eCRF. The following 
immunological assessments will be performed according to the schedule of study assessments 
(Section 5.2).

Serum immunoglobulin concentration over time

IgA

IgE

IgM

Serum complement levels over time

C3

C4

Plasma complement levels over time

C3a

C5a

Serum biomarkers levels over time
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 175 of 353

Serum BAFF levels

Plasma anti-UCB7665 antibodies/IgG depletion assay 

Cytokines

Cytokine samples will be taken at Baseline Visit for all subjects. At subsequent visits, 
cytokine samples will be taken only when the subject experiences infusion reactions. 
Change #44.
Section 12.1.1
Definition of adverse event
Following wordings have been added to paragraph 4:
Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or more bleeding events 
should be reported as AEs.
Change #45.
Section 12.1.3
Description of adverse events
Information of AE evaluation was added:
For recording an AE, CTCAE will be used, and only if it is impossible to assess severity using 
CTCAE, then AE intensity will be assessed using a scale of mild, moderate, or severe.
Change #46.
Section 12.1.6 Pregnancy
Paragraph 1 and sections onward, changed the name of UCB safety reporting department and its 
abbreviation from UCB’s Drug Safety (DS) into UCB’s Patient Safety (PS). 
If an investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the investigator must immediately notify UCB’s Drug Safety (DS) department by providing the 
completed Pregnancy Report and Outcome form (for contact details see Serious Adverse Event 
reporting information at the beginning of this protocol). The subject should be withdrawn from 
the study as soon as pregnancy is known (by positive pregnancy test), and the following should 
be completed:
Has been changed to:
If an investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the investigator must immediately notify UCB’s Patient Safety (PS) department by providing the 
completed Pregnancy Report and Outcome form (for contact details see Serious Adverse Event 
reporting information at the beginning of this protocol). The subject should be withdrawn from 
the study as soon as pregnancy is known (by positive pregnancy test), and the following should 
be completed:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 176 of 353
Change #47.
Suspected transmission of an infectious agent via a medicinal product was added as Section 
12.1.7 and subsequent section numbers were changed accordingly. 
Change #48.
Section 12.1.9 Hypersensitivity and adverse reactions
Paragraph 2
In case of occurrence of a hypersensitivity reaction (not determined by the investigator to be a 
minor local reaction at the infusion site, such as minimal itching) and depending upon its 
severity, appropriate countermeasures will immediately be taken by the investigator. The 
cytokine samples must be taken for infusion reactions.
Has been changed to:
Section 12.1.10
Hypersensitivity and adverse reactions
In case of occurrence of a hypersensitivity reaction (except for local injection site reaction) and 
depending upon its severity, appropriate countermeasures will immediately be taken by the 
investigator. The cytokine samples must be taken for infusion reactions.
Change #49.
Section 12.1.10
Management of severe headache
Paragraph 2, second sentence
Further workup will be performed (if indicated) at the discretion of the investigator and may
include a CT scan and a LP for CSF collection, considering the local guidelines for performing 
LP in patients with ITP.
Has been changed to:
Section 12.1.11
Management of severe headache
Further workup will be performed at the discretion of the investigator and may include eg. a CT 
scan, MRI and/or a LP for CSF collection, considering the local guidelines for performing LP in 
patients with ITP.
Change #50.
Section 12.3
Adverse events of special interest
Paragraph 3, first sentence
Potential Hy’s law, defined as ≥3xULN ALT with co-existing ≥2xULN bilirubin in the absence 
of  ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, must always 
be reported to UCB as an AE of special interest and a serious unexpected AE (ie, without waiting 
for any additional etiologic investigations to have been concluded).
Has been changed to:
Potential Hy’s law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN bilirubin in the 
absence of  ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, must 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 177 of 353
always be reported to UCB as an AE of special interest (ie, without waiting for any additional 
etiologic investigations to have been concluded).
Change #51.
Section 12.7
Laboratory measurements
Paragraphs 1 and 2, first sentence
Blood and urine specimens for routine assay of hematology including coagulation parameters, 
clinical chemistry, and urinalysis testing as well as pregnancy testing will be performed 
according to the Schedule of assessments (Section 5.2) to monitor the safety of subjects.
Prior to randomization, 2 platelet samples will be taken.
Has been changed to:
Blood and urine specimens for routine assay of hematology including coagulation parameters, 
clinical chemistry, urinalysis testing, and pregnancy testing as well as serology testing will be 
performed according to the Schedule of assessments (Section 5.2) to monitor the safety of 
subjects.
Prior to dosing at Visit 2, 2 platelet samples will be taken.
Change #52.
Section 12.7
Laboratory measurements
Table 12-2 has been updated to include serological test
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 178 of 353
Table 12-2: Laboratory measurements
Hematology
Chemistry
Coagulation 
parameters
Urinalysis
Pregnancy test
Basophilsa
Calcium
INR 
pH
Urineb HCG
Eosinophilsa
Phosphate
Prothrombin time
Protein
Serum
c HCG
Neutrophilsa
Chloride
aPTT
Creatinine 
Lymphocytesa
Magnesium
Fibrinogen
Glucose
Others
Monocytesa
Potassium
Ketones
HbA1c
Hematocrit
Sodium
Urobilinogen
HIV
Hemoglobin
BUN
Bilirubin
Hepatitis B
(HBsAg, anti-HBs,
anti-HBc)
Platelet count
AST
Blood
Hepatitis C
(anti-HCV)
RBC count
ALT
Nitrite
WBC count
GGT
Albumin
B- and T-
Lymphocyte count
Total bilirubin 
Leucocytes
Direct bilirubin (if 
indicated)
LDH
Total cholesterol
Triglycerides
ALP
Total protein
Albumin
α1-globulin, 
α2-globulin, and 
β-globulin
Creatinine
hs-CRP
Amylase
ALP=alkaline phosphatase; ALT=alanine aminotransferase; anti-HBc=hepatitis B core antibody; anti-HBs=hepatitis B surface 
antibody; anti-HCV=hepatitis C virus antibody; aPTT=activated partial thromboplastin time; AST=aspartate aminotransferase; 
BUN=blood urea nitrogen;GGT=gamma-glutamyltransferase; HbA1c=glycosylated hemoglobin; HBsAg=hepatitis B surface 
antigen; HCG=human chorionic gonadotropin; HIV=human immunodeficiency virus; hs-CRP=high-sensitivity C-reactive 
protein; INR=International Normalized Ratio; LDH=lactate dehydrogenase; RBC=red blood cell; WBC=white blood cell 
a Absolute as well as percentages for the differential leucocyte counts will be performed.
b Urine pregnancy test will be performed predose on dosing days and at End-of-Study Visit.
c Serum pregnancy test is done at Visit 1 (Screening) and to confirm results of positive urine test if applicable.
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UCB
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 179 of 353
Change #53.
Section 12.7.1
Section for Evaluation of PDILI was added.
Change #54.
Section 12.8.3
Body weight
Subject’s body weight will be determined at Screening and at the End-of-Study Visit. 
Has been changed to:
Section 12.8.3
Body weight and height
Subject’s body weight will be determined at Screening and at the End-of-Study Visit. Height will 
be measured at Screening only.
Change #55.
Section 14.1
Definition of analysis sets
Safety Set (SS):
The SS will consist of all randomized subjects who have received at least 1 infusion (full or 
partial infusion) of IMP and will be used for the demographics and analysis of safety data.
Has been changed to:
Safety Set (SS):
The SS will consist of all subjects who have received at least 1 infusion (full or partial infusion) 
of IMP and will be used for the demographics and analysis of safety data.
Change #56.
Section 14.2
General statistical considerations
Paragraph 1, third sentence
Analyses will be performed by dose arm and overall, unless otherwise stated. In the event that 
the number of infusions in the planned dose arms (3x7mg/kg and 5x4mg/kg) are modified 
following review by the DMC, the data will be summarized based on the actual dose arms 
completing the study. 
Has been changed to:
Analyses will be performed by dose arm, unless otherwise stated. In the event that the number of 
infusions in the planned dose arms (3x7mg/kg and 5x4mg/kg) are modified following review by 
the DMC, the data will be summarized based on the actual dose arms completing the study. 
Change #57.
Section 14.3.2
Other safety analyses
Paragraph 1, third sentence
Adverse events will be categorized by intensity (mild/moderate/severe) and severity according to 
the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grading.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 180 of 353
Has been changed to:
Adverse events will be categorized by severity according to the CTCAE version 4.03 grading. In 
case the CTCAE grading is not available, the intensity (mild/moderate/severe) will be utilized.
Change #58.
Section 14.3.2
Other safety analyses
Paragraph 2, second sentence
For categorized values according to the reference range, shift tables from Baseline to each post 
Baseline time point will be presented.
Has been changed to:
For categorized values according to the reference range, shift tables from Baseline to each post 
Baseline time point will be presented for selected variables to be defined in the SAP.
Change #59.
Section 14.3.2
Other safety analyses
Paragraph 3, last sentence
Descriptive statistics will be presented for ECG value and changes from Baseline over time.
Has been changed to:
Descriptive statistics will be presented for ECG value and changes from Baseline over time
based on the mean of the triplicate assessments at each time point.
Change #60.
Section 14.3.2
Other safety analyses
Paragraph 4, last sentence
Measured values and changes from Baseline will be summarized for all subjects by time point.
Has been changed to:
Measured values and changes from Baseline will be summarized by time point.
Change #61.
Section 14.3.2
Other safety analyses
Paragraph 6
Safety analyses will be presented by dose arms and overall.
Has been changed to:
Safety analyses will be presented by dose arm.
Change #62.
Section 14.4.1
Efficacy analyses
Paragraph 6
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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 181 of 353
The results from the ITP bleeding score will be summarized at each time point and will include 
the scores for each of the three major domains: skin (S), visible mucosae (M), and organs (O) 
and the overall gradation of severity (SMOG).
Has been changed to:
The results from the ITP bleeding scale will be summarized at each time point and will include 
the grades for each of the 3 major domains: skin (S), visible mucosae (M), and organs (O).
Change #63.
Section 14.4.2
Pharmacokinetic analyses
Paragraph 2, third sentence
Descriptive statistics of concentrations will be calculated if at least one third of the individual 
data points are quantifiable (≥LLOQ).
Has been changed to:
Descriptive statistics of concentrations will be calculated if at least two thirds of the individual 
data points are quantifiable (≥LLOQ).
Change #64.
Section 14.4.3
Pharmacodynamic analyses
Paragraph 2
The PD variables will include ITP-specific autoantibody concentrations 
, total IgG, and IgG subclasses. In addition, for total IgG, the maximum change 
from Baseline will be evaluated and summarized. Figures of mean values over time and changes 
from Baseline will be presented.
Has been changed to:
The PD variables will include ITP-specific autoantibodies
total IgG, and IgG subclasses. In addition, for total IgG, the maximum decrease from Baseline 
and minimum value will be evaluated and summarized. Figures of mean values over time and 
changes from Baseline will be presented.
Change #65.
Section 14.4.4
Immunologic variables
Paragraphs 1 and 2
All immunologic variables including concentrations of immunoglobulins (IgA, IgE, and IgM) 
and serum complement parameters (C3, C3a, C4, and C5a) will be summarized by dose arm over 
time (including changes from Baseline) using descriptive statistics. Figures of mean values over 
time and changes from Baseline will be presented.
The results and changes from Baseline for the measurement of ADA will be summarized by dose 
arm; figures will also be presented.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 182 of 353
Has been changed to:
All immunologic variables including concentrations of immunoglobulins (IgA, IgE, and IgM), 
serum (C3 and C4) and plasma (C3a and C5a) complement levels, serum biomarkers 
 
, serum BAFF levels and the results of 
the IgG depletion assay will be summarized by dose arm over time (including changes from 
Baseline) using descriptive statistics. Figures of mean values over time and changes from 
Baseline may be presented.
The ADA status (negative/positive) and changes in relative mass units from Baseline will be 
summarized by dose arm; figures will also be presented.
Change #66.
Section 14.4.5.1
Subject disposition
The number of subjects who were screened, enrolled into the study, and completed/prematurely 
discontinued the study, as well as the reason for discontinuation, will be presented using 
frequency counts and percentages.
Has been changed to:
The number of subjects who were screened, dosed and completed/prematurely discontinued the 
study, as well as the reason for discontinuation, will be presented using frequency counts and 
percentages.
Change #67.
Section 14.4.5.3
Baseline disease characteristics
Definition of complement levels were updated as:

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a).
Change #68.
Section 14.7
Planned interim analysis and data monitoring
Paragraph 1
A DMC will be convened to monitor emergent safety and immunogenicity data during the study.
The DMC will comprise at least 1 external expert, the UCB study physician, the UCB DS 
representative, and a biostatistician. Safety related decisions must be made with the agreement of 
at least the external expert, the UCB study physician, and the UCB DS representative. Decisions 
involving reductions in dose regimen must also have the agreement of the UCB statistician and 
UCB pharmacometrician.
Has been changed to:
A DMC will be convened to monitor emergent safety data during the study. The DMC will 
comprise at least 1 external expert, the UCB study physician, the UCB PS representative, and a 
biostatistician. Safety related decisions must be made with the agreement of at least the external 
expert, the UCB study physician, and the UCB PS representative. Decisions involving reductions 
in dose regimen must also have the agreement of the UCB statistician and UCB 
pharmacometrician.
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 183 of 353
Change #69.
Section 14.7
Planned interim analysis and data monitoring
Paragraph 4, last sentence
If the new dose arm will be initiated and if the 5x4mg/kg will be continued, new subjects will be 
randomized to 1 of the 2 dose arms in an allocation ratio of 1:1 (randomization will stop, once 15 
subjects are treated with UCB7665 4mg/kg dose).
Has been changed to:
If the new dose arm will be initiated and if the 5x4mg/kg will be continued, new subjects will be 
randomized to 1 of the 2 dose arms in an allocation ratio of 1:1 (Once 15 subjects are in the 
4mg/kg group, the remaining subjects will not be randomized. They will be allocated to the 
7mg/kg group).
Change #70.
Section 14.7
Planned interim analysis and data monitoring
Paragraph 9, second sentence
If needed, subsequent DMC meetings will take place and the frequency will be detailed in the 
DMC charter.
Has been changed to:
If needed, subsequent DMC meetings may take place and the frequency will be detailed in the 
DMC charter.
Change #71.
Section 17
REFERENCES
New reference added
Food and Drug Administration. Guidance for Industry. Drug-induced liver injury: premarketing 
clinical evaluation. US Dept of Health and Human Services, Center for Drug Evaluation and 
Research, Center for Biologics Evaluation and Research, 07/2009.
Change #72.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 185 of 353
18.8
Protocol Amendment 2 (not implemented)
Rationale for the amendment
The primary purpose of this substantial amendment is to include an additional cohort to explore 
the PD effect of UCB7665 administered as an sc infusion in subjects with ITP following a more 
frequent dosing regimen (twice weekly).
During this amendment, additional exploratory genomic (DNA and RNA) analyses have been 
added as an optional substudy to evaluate the genomic components of ITP to understand the 
molecular etiology, progression, and treatment of the disease.
UCB considers that the required period for contraceptive use and pregnancy testing can be 
reduced from 3 months to 2 months after the final dose in female subjects due to nonlinear 
kinetics of UCB7665. Following single dose administration at the highest dose tested (7mg/kg) 
no drug was detectable in plasma after 5 days (target mediated disposition). Based on short 
systemic exposure of UCB7665, genotoxicity being not a class effect of monoclonal antibodies, 
and extending contraceptive and pregnancy testing by at least 30 days beyond the end of relevant 
systemic exposure, UCB considers that reducing the required period for contraceptive use and 
pregnancy testing from 3 months to 2 months after the final dose is still adequate to safeguard 
the subjects against possible effects of UCB7665 on human pregnancy.
Minor clarifications were added as necessary, and typographical errors or omissions were 
corrected.
Modifications and changes
Global changes
The following changes were made throughout the protocol:

Addition of a new dose arm 4mg/kg administered twice per week
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 186 of 353

Additional exploratory genomic analyses added as an optional substudy
Specific changes
Change #1
STUDY CONTACT INFORMATION
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Straße 10
40789 Monheim 
GERMANY
Phone:
 (mobile)
Fax:
Has been changed to:
Name:
, MD
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporation Drive, Suite 175
Raleigh
NC 27617, USA
Phone:
Fax:
Change #2
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 187 of 353
STUDY CONTACT INFORMATION
Clinical Project Manager
Name:
Address:
UCB Biopharma SPRL
Allée de la Recherche 60
B-1070 Brussels
BELGIUM
Phone:
Fax:
Has been changed to:
Name:
Address:
UCB BioSciences GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Change #2
LIST OF ABBREVIATIONS
ICH
International Conference on Harmonisation
Has been changed to:
ICH
International Council for Harmonisation
Change #3
LIST OF ABBREVIATIONS
The following additions were made to the list of abbreviations:
AUEC
area under the effect curve
DNA
deoxyribonucleic acid
EOS
End of Study
IGRA
interferon-gamma release assay
LTB
latent tuberculosis
mRNA
messenger ribonucleic acid
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 188 of 353
miRNA
micro ribonucleic acid
PD-PPS
Pharmacodynamic Per Protocol Set
RNA
ribonucleic acid
Change #4
Section 1 SUMMARY
Paragraph #3:
TP0001 is a Phase 2, multicenter, open-label, multiple-dose, 2-dose-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 administered as subcutaneous (sc) doses of 4mg/kg 
or 7mg/kg, in subjects ≥18 years of age with persistent (>3 months up to 12 months after 
diagnosis) or chronic (more than 12 months after diagnosis) primary ITP. 
Has been changed to:
TP0001 is a Phase 2, multicenter, open-label, multiple-dose, multiple-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 administered as subcutaneous (sc) doses of 4mg/kg 
or 7mg/kg, in subjects ≥18 years of age with persistent (>3 months up to 12 months after 
diagnosis) or chronic (more than 12 months after diagnosis) primary ITP.
Change #5
Section 1 SUMMARY
Paragraph #4:
The study is planned to be conducted at approximately 25 sites in Europe and Australia. A total 
of 30 subjects are planned to enter the Dosing Period in the study. The maximum study duration 
for study participation for an individual subject is approximately 16 weeks.
Has been changed to:
The study is planned to be conducted at approximately 30 sites in Europe and Australia. A total 
of 36 subjects are planned to enter the Dosing Period in the study. The maximum study duration 
for study participation for an individual subject is approximately 16 weeks.
Change #6
Section 1 SUMMARY
Paragraph #5:
The study will evaluate 2 dose arms of UCB7665. Subjects in Dose Arm 1 will receive 5 doses 
of UCB7665 4mg/kg sc at 1 week intervals and subjects in Dose Arm 2 will receive 3 doses of 
UCB7665 7mg/kg sc at 1 week intervals.
Has been changed to:
The study is intended to evaluate 3 dose arms of UCB7665. Subjects in Dose Arm 1 will receive 
5 doses of UCB7665 4mg/kg sc at 1 week intervals, subjects in Dose Arm 2 will receive 3 doses 
of UCB7665 7mg/kg sc at 1 week intervals, and subjects in Dose Arm 3 will receive 5 doses of 
UCB7665 4mg/kg sc at 3 to 4 day intervals (ie, twice per week over approximately 2 weeks). 
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 189 of 353
Change #7
Section 1 SUMMARY
Paragraph #6:
The study consists of a Screening Period (up to 4 weeks), Dosing Period of 2 to 4 weeks, and an 
Observation Period of 8 weeks. The Screening Visit corresponds to Visit 1 of the study. The 
Dosing Period will commence at Visit 2 (Baseline Visit), with dosing visits scheduled at weekly 
intervals. The Observation Period will start after the final dose administration with a visit 
scheduled 3 days after the final dose and weekly thereafter (ie, weekly after final dose) for a 
period of 8 weeks. The End-of-Study Visit will be performed at the end of the Observation 
Period, ie, 8 weeks after the final dose of investigational medicinal product (IMP).
Has been changed to:
The study consists of a Screening Period (up to 4 weeks), Dosing Period of 2 to 4 weeks, and an 
Observation Period of 8 weeks. The Screening Visit corresponds to Visit 1 of the study. The 
Dosing Period will commence at Visit 2 (Baseline Visit), with dosing visits scheduled at weekly 
or twice weekly intervals. The Observation Period will start after the final dose administration 
with a visit scheduled 3 days after the final dose and weekly thereafter (ie, weekly after final 
dose) for a period of 8 weeks. The End-of-Study Visit will be performed at the end of the 
Observation Period, ie, 8 weeks after the final dose of investigational medicinal product (IMP).
Change #8
Section 1 SUMMARY
Paragraph #7:
The first 6 subjects will be enrolled in Dose Arm 1 only. While recruitment is ongoing, safety
data for the first 3 subjects up to 7 days after the final dose will be reviewed by a Data 
Monitoring Committee (DMC). During a second DMC meeting, safety data for the first 6 
subjects up to 7 days after the final dose will be reviewed. Following this review, the DMC will 
make a decision on whether to open Dose Arm 2 for enrollment. Once the DMC has approved 
initiation of Dose Arm 2, subsequent subjects will be randomized to 1 of the 2 dose arms using 
an interactive voice/web response system (IXRS). The aim is to have 15 subjects in each dose 
arm. The DMC may also decide to reduce the number of doses in each of the dose arms based on 
review of data during the study. Safety data will also be reviewed on an ongoing basis during the 
study so as to continuously evaluate the safety of subjects.
Has been changed to:
The first 6 subjects will be enrolled in Dose Arm 1 only. While recruitment is ongoing, safety
data for the first 3 subjects up to 7 days after the final dose of the third subject will be reviewed 
by the Data Monitoring Committee (DMC). During a second DMC meeting, all available safety 
data up to cut off date defined as 7 days after the final dose of the sixth subject will be reviewed. 
Following this review, the DMC will make a decision on whether to open Dose Arm 2 for 
enrollment. Once the DMC has approved initiation of Dose Arm 2, the subsequent subjects will 
be randomly assigned in 1:1 ratio to either Dose Arm 1 or Dose Arm 2 using an interactive 
voice/web response system (IXRS). Once 15 subjects are enrolled in Dose Arm 1 and safety data 
review of at least 3 subjects in Dose Arm 2 is done, the subsequent subjects will be randomly
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 190 of 353
assigned in 1:1 ratio to either Dose Arm 2 or Dose Arm 3 using an IXRS. Once 15 subjects are 
enrolled in the Dose Arm 2 or 6 subjects are enrolled in Dose Arm 3, the respective dose arm 
will be closed. The aim is to have 15 subjects in Dose Arms 1 and 2 and 6 subjects in Dose Arm 
3. The DMC may also decide to reduce the number of doses in each of the dose arms based on 
review of data during the study. Safety data will also be reviewed on an ongoing basis during the 
study so as to continuously evaluate the safety of subjects. 
Change #9
Section 1 SUMMARY
Paragraph #13:
The following efficacy variables will be assessed: Response (platelet count ≥30x109/L and at 
least 2-fold increase of the Baseline count) during the study and by visit; Complete Response 
(platelet count ≥100x109/L) during the study and by visit; platelet count ≥50x109/L during the 
study and by visit; the maximum value and maximum increase from Baseline in platelet count 
during the study; value and change from Baseline in platelet count over time; time to Response 
(time from starting treatment to achievement of Response); time to Complete Response (time 
from starting treatment to achievement of Complete Response); time to achieving platelet count 
≥50x109/L; duration of Response (measured from achievement of Response to loss of Response 
[defined as platelet count below 30x109/L or less than 2-fold increase of Baseline platelet 
count]); duration of Complete Response (measured from achievement of Complete Response to 
loss of Complete Response [defined as platelet count below 100x109/L]); duration of platelet 
count ≥50x109/L (measured from achievement of platelet count ≥50x109/L to reduction of 
platelet count below 50x109/L); ITP bleeding score over time; and Patient Reported Outcome 
(PRO), ie, Neurological Fatigue Index for Multiple Sclerosis (NFI-MS) summary score over 
time. Plasma concentration of UCB7665 over time will be assessed as the PK variable. The PD 
variables are minimum value and maximum decrease in total IgG concentration during the study;
IgG subclass concentrations; and ITP-specific autoantibody
in serum over time. Other immunological variables to be evaluated are total IgA, IgE, and IgM 
levels; serum (C3 and C4) and plasma (C3a and C5a) complement levels; ADA status 
(negative/positive) and relative mass units; serum biomarkers 
B cell activating factor (BAFF) levels and the results of the IgG depletion assay; and cytokines 
(for subjects experiencing infusion reactions). Additional exploratory biomarkers may be 
investigated if needed using the samples already available.
Has been changed to:
The following efficacy variables will be assessed: Response (platelet count ≥30x109/L and at 
least 2-fold increase of the Baseline count) during the study and by visit; Complete Response 
(platelet count ≥100x109/L) during the study and by visit; platelet count ≥50x109/L during the 
study and by visit; the maximum value and maximum increase from Baseline in platelet count 
during the study; value and change from Baseline in platelet count over time; Baseline-corrected 
area under the effect curve (AUEC) for platelet count; time to Response (time from starting 
treatment to achievement of Response); time to Complete Response (time from starting treatment 
to achievement of Complete Response); time to achieving platelet count ≥50x109/L; duration of 
Response (measured from achievement of Response to loss of Response [defined as platelet 
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Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 191 of 353
count below 30x109/L or less than 2-fold increase of Baseline platelet count]); duration of 
Complete Response (measured from achievement of Complete Response to loss of Complete 
Response [defined as platelet count below 100x109/L]); duration of platelet count ≥50x109/L
(measured from achievement of platelet count ≥50x109/L to reduction of platelet count below 
50x109/L); Clinical Response (defined as platelet count ≥30x109/L <100x109/L with at least 
2-fold increase from Baseline value and absence of bleeding); time to Clinical Response (time 
from starting treatment to achievement of Clinical Response); duration of Clinical Response 
(measured from achievement of Clinical Response to loss of Clinical Response [loss of Clinical 
Response defined as platelet count <30x109/L or less than 2-fold increase from Baseline platelet 
count or presence of bleeding]); Complete Clinical Response (defined as platelet count 
≥100x109/L and absence of bleeding); time to Complete Clinical Response (time from starting 
treatment to achievement of Complete Clinical Response); duration of Complete Clinical 
Response (measured from achievement of Complete Clinical Response to loss of Complete 
Clinical Response [loss of Complete Clinical Response defined as platelet count <100x109/L or 
presence of bleeding]); no Clinical Response (defined as platelet count <30x109/L and less than 
2-fold increase from Baseline or presence of bleeding); ITP bleeding score over time; and Patient 
Reported Outcome (PRO), ie, Neurological Fatigue Index for Multiple Sclerosis (NFI-MS) 
summary score over time. Plasma concentration of UCB7665 over time will be assessed as the 
PK variable. The PD variables are minimum value and maximum decrease in total IgG 
concentration during the study; IgG subclass concentrations; and ITP-specific autoantibody 
 in serum over time. Other immunological variables to be 
evaluated are total IgA, IgE, and IgM levels; serum (C3 and C4) and plasma (C3a and C5a) 
complement levels; ADA status (negative/positive) and relative mass units; serum biomarkers 
 B cell activating factor (BAFF) levels and the results of the 
IgG depletion assay; B and T lymphocytes; and cytokines (for subjects experiencing infusion 
reactions). Additional exploratory biomarkers may be investigated if needed using the samples 
already available.
Change #10
Section 1 SUMMARY
Paragraph #14:
Exploratory genomic analyses substudy details are added as follows:
During this study, subjects will also have the option of providing additional informed consent for 
exploratory deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) (ie, messenger RNA 
[mRNA] and micro RNA [miRNA]) analyses. Participation in this additional portion of the study
is optional and does not preclude subject’s eligibility for participation in the main study. The 
additional genomic samples must not be collected if the subject has not consented to participate 
in this exploratory genomic substudy.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 192 of 353
Change #11
Section 1 INTRODUCTION
Paragraph #13:
Exploratory genomic analyses substudy details are added as follows:
Subjects will also have the option of providing additional informed consent for exploratory
DNA and RNA (mRNA and miRNA) analyses as described in Section 5.1.1.
Change #12
Section 3.3
Exploratory objectives
NEW bullet:

To evaluate the genomic components of ITP to understand the molecular etiology, 
progression, and treatment of the disease, applicable only for subjects consenting to 
participate in the optional genomic analyses substudy.
Change #13
Section 4.2
Efficacy variables
Additional efficacy variable listed as follows:

Baseline-corrected AUEC for platelet count

Clinical Response: platelet count ≥30x109/L and <100x109/L with at least 2-fold increase 
from Baseline value and absence of bleeding

Time to Clinical Response: time from starting treatment to achievement of Clinical Response

Duration of Clinical Response: measured from achievement of Clinical Response to loss of 
Clinical Response (loss of Clinical Response defined as platelet count <30x109/L or less than 
2-fold increase from Baseline platelet count or presence of bleeding)

Complete Clinical Response: platelet count ≥100x109/L and absence of bleeding

Time to Complete Clinical Response: time from starting treatment to achievement of 
Complete Clinical Response

Duration of Complete Clinical Response: measured from achievement of Complete Clinical 
Response to loss of Complete Clinical Response (loss of Complete Clinical Response defined 
as platelet count <100x109/L or presence of bleeding)

No Clinical Response: platelet count <30x109/L and less than 2-fold increase from Baseline 
or presence of bleeding
Change #14
Section 4.4
Other immunological variables
Additional immunological variable listed as follows:

Lymphocyte counts (B and T)
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 193 of 353
Change #15

Section 5.1
Study description

Paragraphs #1 and #2:
This is a Phase 2, multicenter, open-label, multiple-dose, 2-dose-arm study to evaluate the safety, 
tolerability, and efficacy of UCB7665 in subjects with primary persistent or chronic ITP.
Dose Arm 1: UCB7665 4mg/kg sc (5 doses at an interval of 1 week)
Dose Arm 2: UCB7665 7mg/kg sc (3 doses at an interval of 1 week)
The maximum duration of the study per subject is approximately 16 weeks, consisting of a 
Screening Period (1 to 28 days), a Dosing Period of 2 or 4 weeks, and an Observation Period of 
8 weeks.
Has been changed to:
This is a Phase 2, multicenter, open-label, multiple-dose, multiple-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 in subjects with primary persistent or chronic ITP.
Dose Arm 1 (15 subjects): UCB7665 4mg/kg sc (5 doses at an interval of 1 week)
Dose Arm 2 (15 subjects): UCB7665 7mg/kg sc (3 doses at an interval of 1 week)
Dose Arm 3 (6 subjects): UCB7665 4mg/kg sc (5 doses at intervals of 3 to 4 days)
The maximum duration of the study per subject is approximately 16 weeks, consisting of a 
Screening Period (1 to 28 days), a Dosing Period of 2 to 4 weeks, and an Observation Period of 
8 weeks.
Change #16
Section 5.1
Study description
Paragraph #4:
Dosing Period: The first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in 
the Dose Arm 1 will not be randomized. While recruitment is still ongoing, safety data for the 
first 3 subjects up to 7 days after the final dose of the third subject will be reviewed by the DMC. 
During a second DMC meeting, all available safety data up to cut off date defined as 7 days after 
the final dose of the sixth subject will be reviewed. During these reviews recruitment in the dose 
arm will not be stopped. Following this review, the DMC will make a decision on whether to 
open Dose Arm 2 for enrollment. Once the DMC has approved opening of Dose Arm 2 for 
enrollment, subjects will subsequently be randomized to 1 of the 2 dose arms using IXRS. If the 
new dose arm will be initiated and if the UCB7665 4mg/kg arm will be continued, new subjects 
will be randomized to 1 of the 2 dose arms in an allocation ratio of 1:1 (Once 15 subjects are in 
the 4mg/kg group, the remaining subjects will not be randomized. They will be allocated to the 
7mg/kg group.).
Has been changed to:
Dosing Period: The first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in 
the Dose Arm 1 will not be randomized. While recruitment is still ongoing, safety data for the 
first 3 subjects up to 7 days after the final dose of the third subject in Dose Arm 1 will be 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 194 of 353
reviewed by the DMC. During a second DMC meeting, all available safety data up to cut off date 
defined as 7 days after the final dose of the sixth subject in Dose Arm 1 will be reviewed. During 
these reviews recruitment in the dose arm will not be stopped. Following this review, the DMC 
will make a decision on whether to open Dose Arm 2 for enrollment. Once DMC has approved 
initiation of Dose Arm 2, the subsequent subjects will be randomly assigned in 1:1 ratio to either 
Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in the Dose Arm 1 and 
safety data review of at least 3 subjects in Dose Arm 2 is done, the subjects will subsequently be 
randomly assigned in 1:1 ratio to either Dose Arm 2 or Dose Arm 3 using IXRS. Once 
15 subjects are in the Dose Arm 2 or 6 subjects are enrolled in Dose Arm 3, the respective dose 
arm will be closed. 
Change #17

Section 5.1
Study description
Paragraph #5:
At least 4 interim analyses will be performed. Based on the interim analysis, the DMC will 
assess the safety of UCB7665, determine whether to initiate the UCB7665 7mg/kg dose arm and 
may decide to adapt the dose regimen. Planned dosing may be discontinued for all subjects on a 
dose arm (see Section 6.5). Refer to Section 14.7 for details.
Has been changed to:
At least 4 interim analyses will be performed. Based on the interim analyses, the DMC will 
assess the safety of UCB7665, determine whether to initiate Dose Arm 2, and may decide to 
adapt the dose regimen. Planned dosing may be discontinued for all subjects in a dose arm (see 
Section 6.5). Refer to Section 14.7 for details. 
Change #18

Section 5.1
Study description
Paragraph #6:
In case the DMC recommends reducing the number of doses (infusions) for either the 
UCB7665 4mg/kg dose or UCB7665 7mg/kg dose based on review of safety data, then the 
additional dose arms receiving a reduced number of doses will be considered as additional new 
dose arms for the study.
Has been changed to:
In case the DMC recommends reducing the number of doses (infusions) for any of the 
predefined dose arms based on review of safety data, then the additional dose arms receiving a 
reduced number of doses will be considered as additional new dose arms for the study.
Change #19

NEW Section 5.1.1
Exploratory genomic analyses
During this study, subjects will also have the option of providing additional informed consent for 
exploratory DNA and RNA analyses. Participation in this additional portion of the study is 
optional and does not preclude subject’s eligibility for participation in the main study. The 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 195 of 353
additional genomic samples must not be collected if the subject has not consented to participate 
in this exploratory genomic substudy.
Once subject provides consent, through a separate informed consent form, blood samples will be 
drawn as follows:
For DNA: Blood samples will be collected at Baseline (Visit 2) for all dose arms. Subsequent 
blood sample will be collected prior to the last dose (ie, Visit 7 for Dose Arm 1, Visit 5 for Dose 
Arm 2, and Visit 6 for Dose Arm 3).
For RNA: Blood samples will be collected at following time points for different dose arms: 

Dose Arm 1: Baseline (Visit 2), 3 days after dose 1 (Visit 3), prior to the last dose (Visit 7),
and End of Study Visit (Visit 15).

Dose Arm 2: Baseline (Visit 2), 3 days after dose 1 (Visit 3), prior to the last dose (Visit 5), 
and End of Study Visit (Visit 13). 

Dose Arm 3: Baseline (Visit 2), prior to second dose (Visit 3), prior to the last dose (Visit 6), 
and End of Study Visit (Visit 14).
For each DNA blood sample a volume of 6mL whole blood is needed and for each RNA sample 
a volume of 2.5mL whole blood is needed.
Failure to provide consent to participate in this substudy will not impact subject’s eligibility to 
participate in the main study.
Any exploratory biomarker or genomic analysis will only ever be related to the exploration of 
the underlying causes of ITP in patients, related biology, and drug response. Justification for 
additional genomic analyses is detailed in Section 5.4.6.
Details on the collection, storage, preparation, and shipping of samples will be presented in the 
Laboratory Manual provided separately.
Any results from this analysis will be reported separately and will not form a part of the main 
clinical study report.
Change #20
Section 5.1.3 Planned number of subjects and sites
A total of 30 subjects are planned to enter the Dosing Period in the study. This number should 
allow for an appropriate assessment of the safety and give information on efficacy of the 
treatment for planning of potential future studies. To achieve the required number of eligible 
subjects to enter the Dosing Period, it is anticipated that 40 subjects will need to be screened. 
These subjects will be enrolled at approximately 25 sites. First subject first visit is planned for 
Q1 2016, last subject last visit for Q3 2017.
Has been changed to:
A total of up to 36 subjects are planned to enter the Dosing Periods in the study (15 subjects in 
each of Dose Arms 1 and 2, and 6 subjects in Dose Arm 3). To achieve the required number of 
eligible subjects to enter the Dosing Period, it is anticipated that approximately 54 subjects will 
need to be screened. These subjects will be enrolled at approximately 30 sites. First subject first 
visit is planned for Q1 2016, last subject last visit for Q4 2017.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 196 of 353
Change #21
Section 5.2
Schedule of study assessments
Table 5‒1 presents the tabular scheme of study assessments for UCB7665 4mg/kg dose arm and 
Table 5‒2 presents the tabular scheme of study assessments for UCB7665 7mg/kg dose arm. 
Table 5‒3 presents the assessments to be performed on dosing days.
Has been changed to:
Table 5-1 presents the tabular scheme of study assessments for the weekly UCB7665 4mg/kg 
dose arm (Dose Arm 1), Table 5-2 presents the tabular scheme of study assessments for the 
weekly UCB7665 7mg/kg dose arm (Dose Arm 2), and Table 5-3 presents the tabular scheme of 
study assessments for the twice weekly UCB7665 4mg/kg dose arm (Dose Arm 3). Table 5-4
presents the assessments to be performed on dosing days.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 197 of 353
Change #22
Section 5.2
Schedule of study assessments
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
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1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consent
X
Demographic data
X
Verification of 
inclusion/exclusion 
criteria
X
X
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withdrawal check (local 
laboratory)f
X
X
X
X
X
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X
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X
X
X
X
X
X
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medical/procedures 
history
X
ITP history
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 198 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
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EOS/ 
EWc
Day
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1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
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±2dd
±2dd
±2dd
±1d
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±2de
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±2de
±2de
±2de
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
X
X 
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 199 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
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EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
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Window
±1d
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±2dd
±2dd
±1d
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±2de
±2de
±2de
±2de
±2de
Serology test for HIV, 
hepatitis B, and hepatitis 
C
X
Blood sample for 
cytokines
X
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
X
X
Call to IXRS for treatment 
kit number
X
X
X
X
X
Administration of IMP
X
X
X
X
X
Blood sampling for 
plasma concentration of 
UCB7665
X
X
X
X
X
X
X
X
Anti-UCB7665 
antibodies/IgG depletion 
assay
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 200 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serum complements (C3 
and C4) and plasma 
complements (C3a and 
C5a)
X
X
X
X
Serum biomarkers 
 
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum biomarkers 
X
X
X
X
X
X
Serum BAFF levels
X
X
X
X
X
X
X
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
IgA, IgM, IgEl
X
X
X
X
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X
X
X
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X
X
X
X
X
X
X
X
X
X
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X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 201 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Headache questionnairen
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewo
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human immunodeficiency virus;
Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar 
puncture; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
a Frequency of assessments on dosing days is detailed in Table 5-3.  
b Visits 10, 12, and 14 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date.
f Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
g The first 6 subjects will be enrolled in the Dose Arm 1 group only. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the 
DMC. Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, subjects subsequently enrolled will 
be randomly assigned subsequently to 1 of the 2 dose arms using an IXRS until 15 subjects are in Dose Arm 1.
h Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
i A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 202 of 353
j At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
k Blood sample for cytokines will be obtained only in case of infusion reactions.
l In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 7 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
m
n This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to  CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
o A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
Has been changed to:
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of 
inclusion/exclusion 
criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)g
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 203 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Randomizationh
X
Withdrawal criteriai
X
X
X
X
X
X
General 
medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationj
X
X
X
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
X
X
X 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 204 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xl
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis 
C
X
Blood sample for 
cytokines
X
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Whole blood sample for 
DNA (optional)
X
X
Whole blood sample for 
RNA (optional)
X
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
X
X
Call to IXRS for treatment
kit number
X
X
X
X
X
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This document cannot 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 205 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Administration of IMP
X
X
X
X
X
Blood sampling for 
plasma concentration of 
UCB7665
X
X
X
X
X
X
X
X
Anti-UCB7665 
antibodies/IgG depletion 
assay
X
X
X
X
X
X
X
X
X
X
X
X
Serum complements (C3 
and C4) and plasma 
complements (C3a and 
C5a)
X
X
X
X
Serum biomarkers 
 
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum biomarkers 
X
X
X
X
X
X
Serum BAFF levels
X
X
X
X
X
X
X
REDACTED COPY 
X
COP
X
PY
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X
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X
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X
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marketing authorization application and any extensions or variations thereof.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 206 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
IgA, IgM, IgEn
X
X
X
X
ITP-specific 
autoantibodieso
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairep
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewq
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring; 
DNA=deoxyribonucleic acid; Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response 
system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
a Frequency of assessments on dosing days is detailed in Table 5-4.  
b Visits 10, 12, and 14 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
REDACTED COPY 
X
COP
X
PY
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CT
R
AC
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keting authorization application and any extensions or variations thereof.
15 Fe
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 207 of 353
e The visit windows in the Observation Period are relative to the final dosing visit date.
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h The first 6 subjects will be enrolled in the Dose Arm 1 group only. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the 
DMC. Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, the subsequent subjects will be 
randomly assigned in 1:1 ratio to either Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in Dose Arm 1 and safety data review of at 
least 3 subjects in Dose Arm 2 is done, the subsequent subjects will be randomly assigned in 1:1 ratio to either Dose Arm 2 or Dose Arm 3 using an IXRS. 
Once 15 subjects are in Dose Arm 2 or 6 subjects are enrolled in Dose Arm 3, the respective dose arm will be closed.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted. 
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m Blood sample for cytokines will be obtained only in case of infusion reactions.
n In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 7 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
o
p This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
q A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
ACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 208 of 353
Change #23
Section 5.2
Schedule of study assessments
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consent
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
X
Platelets for inclusion/withdrawal 
check (local laboratory) f
X
X
X
Randomizationg
X
Withdrawal criteriah
X
X
X
X
General medical/procedures history
X
ITP history
X
Prior and concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 209 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters (hematology, 
chemistry, urinalysis)
Xj
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, hepatitis B, and 
hepatitis C
X
Blood sample for cytokines
X
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
Call to IXRS for treatment kit number
X
X
X
Administration of IMP
X
X
X
REDACTED COPY 
O
D C
X
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X
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X
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X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 210 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Blood sampling for plasma 
concentration of UCB7665
X
X
X
X
X
X
Anti-UCB7665 antibodies/IgG 
depletion assay
X
X
X
X
X
X
X
X
X
X
Serum complements (C3 and C4) and 
plasma complements (C3a and C5a)
X
X
X
X
Serum biomarkers 
 
X
X
X
X
X
X
X
X
X
X
X
Serum biomarkers 
X
X
X
X
Serum BAFF levels
X
X
X
X
X
Immunoglobulins (total IgG, IgG 
subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEl
X
X
X
X
ITP-specific autoantibodiesm
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
REDACTED COPY
X
OPY
X
Y
C
 
X
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X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 211 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Headache questionnairen
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewo
X
AE=adverse event; BAFF=B cell activating factor; BL=baseline; CSF=cerebrospinal fluid CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human immunodeficiency virus;
Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar 
puncture; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
a Frequency of assessments on dosing days is detailed in Table 5-3.
b Visits 8, 10, and 12 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date. 
f Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
g The first 6 subjects will be enrolled in the Dose Arm 1 group. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the DMC. 
Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, subjects subsequently enrolled will be 
randomly assigned to one of the dose arms using an IXRS until 15 subjects are in Dose Arm 1.
h Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
i A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
j At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
ED COPY
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 212 of 353
k Blood sample for cytokines will be obtained only in case of infusion reactions.
l In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 5 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
m
n This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
o A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
Has been changed to:
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
X
Platelets for inclusion/withdrawal 
check (local laboratory) g
X
X
X
Randomizationh
X
REDACTED COPY 
g w
Y
g w
PY
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ED
se 
2
TE
2
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 213 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Withdrawal criteriai
X
X
X
X
General medical/procedures history
X
ITP history
X
Prior and concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationj
X
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters (hematology, 
chemistry, urinalysis)
Xl
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, hepatitis B, and 
hepatitis C
X
REDACTED COPY
X
OPY
X
Y 
CO
D C
D 
D
DACT
DAC
X
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X
DA
DA
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any marketing authorization application and any extensions or variations thereof.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 214 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Blood sample for cytokines
X
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Whole blood sample for DNA 
(optional)
X
X
Whole blood sample for RNA 
(optional)
X
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
Call to IXRS for treatment kit number
X
X
X
Administration of IMP
X
X
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
X
X
X
Anti-UCB7665 antibodies/IgG 
depletion assay
X
X
X
X
X
X
X
X
X
X
Serum complements (C3 and C4) and 
plasma complements (C3a and C5a)
X
X
X
X
Serum biomarkers 
 
X
X
X
X
X
X
X
X
X
X
X
REDACTED COPY
X
OP
Xm
PY
m
Y 
X
O
X
CO
D C
TE
DAC
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R
arketing authorization application and any extensions or variations thereof.
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This document can


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 215 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serum biomarkers 
X
X
X
X
Serum BAFF levels
X
X
X
X
X
Immunoglobulins (total IgG, IgG 
subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEn
X
X
X
X
ITP-specific autoantibodieso
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairep
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewq
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response 
system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
Frequency of assessments on dosing days is detailed in Table 5-4.
b Visits 8, 10, and 12 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
REDACTED COPY
X
OPY
X
Y
C
 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 216 of 353
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date. 
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h The first 6 subjects will be enrolled in the Dose Arm 1 group. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the DMC. 
Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, the subsequent subjects will be randomly 
assigned in 1:1 ratio to either Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in Dose Arm 1 and safety data review of at least 3 
subjects in Dose Arm 2 is done, the subsequent subjects will be randomly assigned in 1:1 ratio to either Dose Arm 2 or Dose Arm 3 using an IXRS. Once 15 
subjects are in Dose Arm 2 or 6 subjects are enrolled in Dose Arm 3, the respective dose arm will be closed.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m Blood sample for cytokines will be obtained only in case of infusion reactions.
n In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 5 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
o
p This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
q A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 217 of 353
Change #24
Section 5.2
Schedule of study assessments
NEW table:
Table 5-3:
Schedule of assessments for the UCB7665 4mg/kg twice weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Dose 3
Dose 4
Dose 5
Visit 
1
2a
3a
4a
5a
6a
7
8
9b
10
11b
12
13b
14
BL 
Visit
EOS/EW
c
Day
-28 to -1
1
4
8
11
15
18
22
29
36
43
50
57
71
Week
1
1
2
2
3
3
4
5
6
7
8
9
11
Visit 
Window
+1dd
+1dd
+1dd
+1dd
±1d
±2d
e
±2de
±2de
±2de
±2de
±2de
±2de
Written informed 
consentf
X
Demographic data
X
Verification of 
inclusion/exclusion 
criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)g
X
X
X
X
X
Randomizationh
X
Withdrawal criteriai
X
X
X
X
X
General 
medical/procedures 
history
X
REDACTED COPY
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PY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 218 of 353
Table 5-3:
Schedule of assessments for the UCB7665 4mg/kg twice weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Dose 3
Dose 4
Dose 5
Visit 
1
2a
3a
4a
5a
6a
7
8
9b
10
11b
12
13b
14
BL 
Visit
EOS/EW
c
Day
-28 to -1
1
4
8
11
15
18
22
29
36
43
50
57
71
Week
1
1
2
2
3
3
4
5
6
7
8
9
11
Visit 
Window
+1dd
+1dd
+1dd
+1dd
±1d
±2d
e
±2de
±2de
±2de
±2de
±2de
±2de
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationj
X
X
X
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
X
X
X
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xl
X
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
X
REDACTED COPY 
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ACT
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X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 219 of 353
Table 5-3:
Schedule of assessments for the UCB7665 4mg/kg twice weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Dose 3
Dose 4
Dose 5
Visit 
1
2a
3a
4a
5a
6a
7
8
9b
10
11b
12
13b
14
BL 
Visit
EOS/EW
c
Day
-28 to -1
1
4
8
11
15
18
22
29
36
43
50
57
71
Week
1
1
2
2
3
3
4
5
6
7
8
9
11
Visit 
Window
+1dd
+1dd
+1dd
+1dd
±1d
±2d
e
±2de
±2de
±2de
±2de
±2de
±2de
hepatitis B, and hepatitis 
C
Blood sample for 
cytokines
X
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Whole blood sample for 
DNA (optional)
X
X
Whole blood sample for 
RNA (optional)
X
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
X
X
Call to IXRS for 
treatment kit number
X
X
X
X
X
Administration of IMP
X
X
X
X
X
Blood sampling for 
plasma concentration of 
UCB7665
X
X
X
X
X
X
X
Anti-UCB7665 
antibodies/IgG depletion 
assay
X
X
X
X
X
X
X
X
X
X
X
REDACTED COPY 
Y
CO
D C
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4
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This document cannot be
t c


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 220 of 353
Table 5-3:
Schedule of assessments for the UCB7665 4mg/kg twice weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Dose 3
Dose 4
Dose 5
Visit 
1
2a
3a
4a
5a
6a
7
8
9b
10
11b
12
13b
14
BL 
Visit
EOS/EW
c
Day
-28 to -1
1
4
8
11
15
18
22
29
36
43
50
57
71
Week
1
1
2
2
3
3
4
5
6
7
8
9
11
Visit 
Window
+1dd
+1dd
+1dd
+1dd
±1d
±2d
e
±2de
±2de
±2de
±2de
±2de
±2de
Serum complements (C3 
and C4) and plasma 
complements (C3a and 
C5a)
X
X
X
X
Serum biomarkers 
X
X
X
X
X
X
X
X
X
X
X
X
Serum biomarkers 
X
X
X
X
X
Serum BAFF levels
X
X
X
X
X
X
X
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEn
X
X
X
X
ITP-specific 
autoantibodieso
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
REDACTED COPY 
Y
D C
X
ACT
X
CTE
DA
R
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ot
This document can
an


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 221 of 353
Table 5-3:
Schedule of assessments for the UCB7665 4mg/kg twice weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Dose 3
Dose 4
Dose 5
Visit 
1
2a
3a
4a
5a
6a
7
8
9b
10
11b
12
13b
14
BL 
Visit
EOS/EW
c
Day
-28 to -1
1
4
8
11
15
18
22
29
36
43
50
57
71
Week
1
1
2
2
3
3
4
5
6
7
8
9
11
Visit 
Window
+1dd
+1dd
+1dd
+1dd
±1d
±2d
e
±2de
±2de
±2de
±2de
±2de
±2de
Headache questionnairep
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewq
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid ; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response 
system; LP=lumbar puncture; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis;
RNA=ribonucleic acid;
a Frequency of assessments on dosing days is detailed in Table 5-4.
b Visits 9, 11, and 13 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of +1 day is allowed for the dosing visits, with at least 3 days in between 2 successive doses. 
e The visit windows in the Observation Period are relative to the final dosing visit date. 
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h Dose Arm 3 will be opened once 15 subjects are enrolled in Dose Arm 1 and safety data review of at least 3 subjects in Dose Arm 2 is done. Subsequent 
subjects will be randomly assigned in 1:1 ratio to either Dose Arm 2 or Dose Arm 3 using an IXRS. Once 15 subjects are in Dose Arm 2 or 6 subjects are 
enrolled in Dose Arm 3, the respective dose arm will be closed.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
ED COPY 
X
OPY
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Y
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 222 of 353
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m Blood sample for cytokines will be obtained only in case of infusion reactions.
n In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 6 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
o
p This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
q A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
Change #25
Section 5.2
Schedule of study assessments
Table 5-3:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of infusion
4h after end of infusion
Withdrawal criteria
X
Platelet count (local laboratory) for inclusion check 
at Visit 2 and for withdrawal criterion at other 
dosing visits
X
Prior and concomitant medications
X
Concomitant medical procedures
X
Vital signsa
X
X
X
X
Physical examination
X
12-lead ECG
X
Hematology 
X
Clinical chemistry
X
REDACTED COPY 
g day
CTED
g day
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This document cannot 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 223 of 353
Table 5-3:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of infusion
4h after end of infusion
Urinalysis
X
Urine pregnancy test
X
Immunoglobulinsb
X
ITP-specific autoantibodiesc
X
Blood sampling for UCB7665 plasma 
concentration
X
Anti-UCB7665 antibodies/IgG depletion assay
X
Serum (C3 and C4) and plasma complements (C3a 
and C5a)d
X
Serum biomarkers 
X
X
X
Serum BAFF levels
X
X
X
Blood sampling for cytokinese
X
ITP bleeding scale
X
AEs
X
X
X
X
NFI-MSf
X
AE=adverse event; BAFF=B cell activating factor; ECG=electrocardiogram; h=hours; Ig=immunoglobulin; IMP=investigational medicinal product; 
ITP=immune thrombocytopenia; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
 PRO=Patient Reported 
Outcomes; 
a In addition to time points mentioned, vital signs will be evaluated every 15 minutes during infusion. Respiratory rate will be assessed only once predose.
b Total IgG and IgG subclasses. 
c Evaluation of ITP-specific autoantibodies will be performed prior to dose 1 only. 
d Serum and plasma complement levels will be assessed prior to dose 1 and dose 3 only.
e Blood sample for Baseline cytokine values will be obtained at Visit 2 for all subjects at predose and at other visits in case of infusion reactions.
f PRO endpoint (NFI-MS) will be assessed prior to dose 1 only.
REDACTED COPY 
OP
TE
AC
AC
AC
AC
AC
RE
eting authorization application and any extensions or variations thereof.
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G=electr
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s will be
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s will be
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 224 of 353
Has been changed to:
Table 5‒4:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of infusion
4h after end of infusion
Withdrawal criteria
X
Platelet count (local laboratory) for inclusion check 
at Visit 2 and for withdrawal criterion at other 
dosing visits
X
Prior and concomitant medications
X
Concomitant medical procedures
X
Vital signsa
X
X
X
X
Physical examination
X
12-lead ECGb
X
Hematology 
X
Clinical chemistry
X
Urinalysis
X
Urine pregnancy test
X
Immunoglobulinsc
X
ITP-specific autoantibodiesd
X
Blood sampling for UCB7665 plasma 
concentration
X
Anti-UCB7665 antibodies/IgG depletion assay
X
Serum (C3 and C4) and plasma complements (C3a 
and C5a)e
X
Serum biomarkers 
X
X
X
Serum BAFF levels
X
X
X
REDACTED COPY 
Y
OP
D
CT
AC
DA
R
keting authorization application and any extensions or variations thereof.
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here
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on
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ons 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 225 of 353
Table 5‒4:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of infusion
4h after end of infusion
Blood sampling for cytokinesf
X
Whole blood sample for DNA and RNA (optional)g
X
ITP bleeding scale
X
AEs
X
X
X
X
NFI-MSh
X
AE=adverse event; BAFF=B cell activating factor; DNA=deoxyribonucleic acid; ECG=electrocardiogram; h=hours; Ig=immunoglobulin; IMP=investigational 
medicinal product; ITP=immune thrombocytopenia; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
PRO=Patient Reported Outcomes; RNA=ribonucleic acid; 
a In addition to time points mentioned, vital signs will be evaluated every 15 minutes during infusion. Respiratory rate will be assessed only once predose.
b The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
c Total IgG and IgG subclasses. 
d Evaluation of ITP-specific autoantibodies will be performed prior to dose 1 only. 
e Serum and plasma complements (C3a and C5a) will be assessed prior to dose 1 and dose 3 only.
f Blood sample for Baseline cytokine values will be obtained at Visit 2 for all subjects at predose and at other visits in case of infusion reactions.
g For DNA, samples are taken at Baseline (Visit 2) and last dose only. For RNA, samples are taken at Baseline (Visit 2), Visit 3, at last dose, and End of Study 
Visit. All samples collected prior to dosing (if applicable for visit).
h PRO endpoint (NFI-MS) will be assessed prior to dose 1 only.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 226 of 353
Change #26
Section 5.3
Schematic diagram
Figure 5‒1: Schematic diagram
DMC=Data Monitoring Committee; EOS=End of Study; sc=subcutaneous
RED
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 227 of 353
Has been changed to:
Figure 5‒1: Schematic diagram
DMC=Data Monitoring Committee; EOS=End of Study; sc=subcutaneous
Note: 2x4mg/kg refers to UCB7665 4mg/kg dose given twice weekly.
Change #27
Section 5.4.5
Rationale for dose selection
Paragraph #5:
Therefore, doses of UCB7665 4mg/kg given once weekly for 5 weeks and UCB7665 7mg/kg 
given once weekly for 3 weeks have been selected to evaluate the safety, tolerability and effect 
on platelet count in subjects with primary persistent or chronic ITP.
Has been changed to:
Therefore, doses of UCB7665 4mg/kg given once weekly for 5 weeks and UCB7665 7mg/kg 
given once weekly for 3 weeks have been selected as the initial doses to evaluate the safety, 
tolerability and effect on platelet count in subjects with primary persistent or chronic ITP. 
However, modelled data has shown a similar IgG reduction in a 4mg/kg twice weekly dosing 
regimen as in a 7mg/kg weekly dosing regimen. Therefore, a third dosing arm of UCB7665 
4mg/kg twice weekly has been integrated into the study design to explore the PD effect of 
UCB7665 administered as an sc infusion in subjects with ITP following a more frequent dosing 
regimen. This dose arm will be initiated after safety data review of at least 3 subjects in Dose 
Arm 2 is done and Dose Arm 1 has completed enrollment of 15 subjects.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 228 of 353
Change #28
NEW Section 5.4.6
Justification for additional genomic analyses
DNA analysis
A genetic component in ITP has long been suspected to predispose some persons to develop ITP 
when exposed to a provocative event.
Further, the hypothesis of underlying genetic risk for ITP is supported by rare anecdotal and case 
reports of familial ITP. Affected members of these families present with ITP that meets the 
clinical criteria for primary ITP, but demonstrates a convincing pattern of inheritance. A 2006 
review of the Pediatric and Adult Registry of Chronic ITP (PARC-ITP) (Johnsen, 2012) found 
that 10 of 445 (2.2%) of pediatric patients reported a positive family history of ITP. However, 
identification of susceptibility genes in ITP, via family linkage studies or genome wide 
association studies, have not yet been forthcoming, likely due to the rarity of familial ITP 
families available for study and the heterogeneity of ITP sporadic cases. Identification and 
characterization of a genetic and/or epigenetic component of familial ITP will lead to important 
clues into the pathogenesis of more common forms of ITP and possibly advance understanding 
of drug response phenotypes. 
RNA analysis
Gene expression (mRNA) analyses have identified distinct gene transcription signatures from 
whole blood associated with many autoimmune diseases including rheumatoid arthritis, systemic 
lupus erythematosus, and ITP. Such signatures have provided molecular insight into disease 
biology and can facilitate patient stratification via gene expression panels predictive of 
therapeutic response and clinical outcomes. 
Collection of blood for RNA analysis will enable identification of candidate markers for 
treatment effect and safety, and determine the feasibility of patient stratification.
MicroRNA analysis
MicroRNA are short (19-25 nucleotides) evolutionarily conserved single-stranded RNA 
molecules that regulate the expression of genes involved in diverse biological processes. The 
effect of miRNA on mRNA is mediated through the binding of the miRNA to the target mRNA 
ribonucleoprotein complex resulting in altered expression and decreased protein translation.  
Regulated miRNA in ITP significantly affect both gene and protein expression in T cells, 
indicating that they may be important regulatory molecules involved in the loss of immune 
tolerance in ITP.
In summary, the genetic, epigenetic, and genomic elements of ITP are complex and require 
further elucidation to understand the cause, progression, and appropriate treatment of ITP. 
Through the voluntary collection of blood DNA/and RNA samples from consenting subjects, this 
substudy will help enable further investigation of this complex disease.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 229 of 353
Change #29
Section 6.1
Inclusion criteria
7. Female subjects of childbearing potential must have a negative serum pregnancy test at the 
Screening Visit, which is confirmed to be negative by urine testing prior to the first dose of 
IMP at Week 1 (Visit 2) and prior to further dosing at each study visit thereafter. 
Female subjects of childbearing potential must agree to use a highly effective method of 
birth control, during the study and for a period of 3 months after their final dose of IMP. 
Highly effective forms of birth control are methods which achieve a failure rate of less than 
1% per year when used consistently and correctly. Highly effective methods of birth control 
include:
…
Has been changed to:
7. Female subjects of childbearing potential must have a negative serum pregnancy test at the 
Screening Visit, which is confirmed to be negative by urine testing prior to the first dose of 
IMP at Week 1 (Visit 2) and prior to further dosing at each study visit thereafter. 
Female subjects of childbearing potential must agree to use a highly effective method of 
birth control, during the study and for a period of 2 months after their final dose of IMP. 
Highly effective forms of birth control are methods which achieve a failure rate of less than 
1% per year when used consistently and correctly. Highly effective methods of birth control 
include:
…
Change #30
Section 6.5
Study stopping rules
Paragraph #2:
More detailed criteria for stopping a cohort will be defined in the DMC charter.
Has been changed to:
More detailed criteria for stopping a dose arm will be defined in the DMC charter.
Change #31
Section 7.2
Treatment to be administered
Paragraph #1: Dose Arm 3 details added as follows:
Subjects in the Dose Arm 3 will receive 5 sc doses of UCB7665 4mg/kg at 3 to 4 day intervals 
(ie, approximately twice a week).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 230 of 353
Change #32
Section 7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Conference on 
Harmonisation (ICH) guidelines on GCP and GMP and will include any locally required 
statements. If necessary, labels will be translated into the local language.
Has been changed to:
Clinical drug supplies will be labeled in accordance with the current International Council for 
Harmonisation (ICH) guidelines on GCP and GMP and will include any locally required 
statements. If necessary, labels will be translated into the local language.
Change #33
Section 7.10
Randomization and numbering of subjects
Paragraph #2:
The first 6 subjects (and those treated before DMC assessment after the 6 subjects) will not be 
randomized. Once the DMC has approved opening of Dose Arm 2 for enrollment, subsequent 
subjects will be randomized to 1 of the 2 dose arms in a 1:1 ratio. Once 15 subjects are in the 
4mg/kg group, the remaining subjects will not be randomized. They will be allocated to the 
7mg/kg group.
Has been changed to:
The first 6 subjects (and those treated before DMC assessment after the 6 subjects) will not be 
randomized. Once the DMC has approved opening of Dose Arm 2 for enrollment, subsequent 
subjects will be randomly assigned to 1 of the 2 dose arms (ie, Dose Arm 1 and Dose Arm 2) in a 
1:1 ratio. Once 15 subjects are enrolled in the Dose Arm 1 and safety data review of at least 
3 subjects in Dose Arm 2 is done, the remaining subjects will be randomly assigned in 1:1 ratio 
to either Dose Arm 2 or Dose Arm 3. Once 15 subjects are enrolled in the Dose Arm 2 or 
6 subjects are enrolled in Dose Arm 3, the respective dose arm will be closed. 
Change #34
Section 8.1.1 Visit 1 (Day -28 to -1) Screening Visit
Has been changed to:
Section 8.1.1 Visit 1 (Day -28 to -1) Screening Visit (all Dose Arms)
Detail regarding informed consent process for exploratory genomic analyses added as follows:
Subjects will also have the option of providing additional voluntary informed consent for 
collection of whole blood samples for exploratory DNA and RNA analyses.
NEW bullet:

Obtain informed consent for substudy involving DNA and RNA analyses
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 231 of 353
Change #35
Section 8.2
Dosing Period 
Has been changed to:
Section 8.2
Dosing Period for Dose Arms 1 and 2 (weekly dosing regimen)
Change #36
Section 8.2.1 Visit 2 (Week 1/Day 1) Baseline Visit
Paragraphs #2, #3, and #4:
Eligible subjects will be treated with IMP at Visit 2. The first 6 subjects will be enrolled in Dose 
Arm 1, subsequent subjects will be randomized to 1 of the 2 dose arms. Once 15 subjects are in 
Dose Arm 1, the remaining subjects will not be randomized. They will be allocated to Dose 
Arm 2. 
Eligible subjects will be treated with IMP at Visit 2. The first 6 subjects will be enrolled in Dose 
Arm 1, subsequent subjects will be randomized to 1 of the 2 dose arms. Once 15 subjects are in 
Dose Arm 1, the remaining subjects will not be randomized. They will be allocated to Dose 
Arm 2. 
Subjects allocated to Dose Arm 1 (UCB7665 4mg/kg sc) will receive a total of 5 doses of IMP at 
Visit 2 (Day 1, Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), and Visit 7 
(Week 5). 
Subjects allocated to Dose Arm 2 (UCB7665 7mg/kg sc) will receive a total of 3 doses of IMP at 
Visit 2 (Day 1, Week 1), Visit 4 (Week 2), and Visit 5 (Week 3). 
Has been changed to:
Section 8.2.1 Visit 2 (Week 1/Day 1) Baseline Visit [UCB7665 4mg/kg weekly and UCB7665 
7mg/kg weekly]
Eligible subjects will be treated with IMP at Visit 2. The first 6 subjects will be enrolled in Dose 
Arm 1; subsequent subjects will be randomly assigned to 1 of the 2 dose arms (ie, Dose Arm 1 
and Dose Arm 2). Once 15 subjects are in Dose Arm 1 and at least 3 subjects are in Dose Arm 2, 
the remaining subjects will be randomly assigned in 1:1 ratio to either Dose Arm 2 or Dose 
Arm 3. Once 15 subjects are in Dose Arm 2 or 6 subjects are enrolled in Dose Arm 3, the 
respective dose arm will be closed.
Subjects allocated to Dose Arm 1 (UCB7665 4mg/kg weekly sc) will receive a total of 5 doses of 
IMP at Visit 2 (Day 1, Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), and 
Visit 7 (Week 5). 
Subjects allocated to Dose Arm 2 (UCB7665 7mg/kg weekly sc) will receive a total of 3 doses of 
IMP at Visit 2 (Day 1, Week 1), Visit 4 (Week 2), and Visit 5 (Week 3). 
NEW bullet:

Collection of whole blood for exploratory DNA and RNA analyses
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 232 of 353
Change #37
Section 8.2.2 Visit 3 (Week 1/Day 4)
Has been changed to:
Section 8.2.2 Visit 3 (Week 1/Day 4) [UCB7665 4mg/kg weekly and UCB7665 7mg/kg 
weekly]
New bullet:

For Dose Arm 1 and 2, collection of whole blood for exploratory RNA analyses 
Change #38
Section 8.2.3 Visit 4 (Week 2/Day 8)
Has been changed to:
Section 8.2.3 Visit 4 (Week 2/Day 8) [UCB7665 4mg/kg weekly and UCB7665 7mg/kg 
weekly]
Change #39
Section 8.2.4 Visit 5 (Week 3/Day 15)
Has been changed to:
Section 8.2.4 Visit 5 (Week 3/Day 15) [UCB7665 4mg/kg weekly and UCB7665 7mg/kg 
weekly]
New bullet:

For Dose Arm 2 only, collection of whole blood for exploratory DNA and RNA analyses
Change #40
Section 8.2.5 Visit 6 (Week 4/Day 22) [UCB7665 4mg/kg only]
Has been changed to:
Section 8.2.5 Visit 6 for Dose Arm 1 (Week 4/Day 22) [UCB7665 4mg/kg only]
Change #41
Section 8.2.6 Visit 7 (Week 5/Day 29) [UCB7665 4mg/kg only]
Has been changed to:
Section 8.2.6 Visit 7 for Dose Arm 1 (Week 5/Day 29) [UCB7665 4mg/kg only]
New bullet:

For Dose Arm 1 only, collection of whole blood for DNA and RNA analyses
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 233 of 353
Change #42
NEW Sections 8.3, 8.3.1, 8.3.2, 8.3.3, 8.3.4, and 8.3.5:
Section 8.3
Dosing for Dose Arm 3 (twice weekly dosing regimen)
Subjects allocated to Dose Arm 3 (UCB7665 4mg/kg twice weekly sc) will receive a total of 
5 doses of IMP at Visit 2 (Day 1, Week 1), Visit 3 (Day 4, Week 1), Visit 4 (Day 8, Week 2), 
Visit 5 (Day 11, Week 2), and Visit 6 (Day 15, Week 3). 
Section 8.3.1 Visit 2 (Week 1 Day 1) Baseline Visit [UCB7665 4mg/kg twice weekly]
The same conditions and assessments are required at this Visit as are detailed in Section 8.2.1.
Section 8.3.2 Visit 3 (Week 1/Day 4) [UCB7665 4mg/kg twice weekly]
This is the second dosing visit and a window of +1 day is allowed for this visit. However, there 
should be a minimum of 3 days (72 hours) interval between two doses. 
The assessments at this visit are identical to those detailed in Section 8.2.3. Additional to the 
assessments mentioned in Section 8.2.3, whole blood samples will be collected for RNA 
analyses.
Section 8.3.3 Visit 4 (Week 2/Day 8) [UCB7665 4mg/kg twice weekly]
This is the third dosing visit and a window of +1 day is allowed for this visit, relative to Dose 1 
at the Visit 2 date. However, there should be a minimum of 3 days (72 hours) interval between 
two doses.
The assessments at this visit are identical to those detailed in Section 8.2.4.
Section 8.3.4 Visit 5 (Week 2/Day 11) [UCB7665 4mg/kg twice weekly]
This is the fourth dosing visit and a window of +1 day is allowed for this visit, relative to Dose 1 
at the Visit 2 date. However, there should be a minimum of 3 days (72 hours) interval between 
two doses.
The assessments at this visit are identical to those detailed in Section 8.2.5.
Section 8.3.5 Visit 6 (Week 3/Day 15) [UCB7665 4mg/kg twice weekly]
This is the fifth dosing visit and a window of +1 day is allowed for this visit, relative to Dose 1 at 
the Visit 2 date. However, there should be a minimum of 3 days (72 hours) interval between two 
doses.
The assessments at this visit are identical to those detailed in Section 8.2.6. Blood samples will 
be collected for DNA and RNA analyses.
Change #43
Section 8.3
Observation Period
Paragraph #2:
For UCB7665 4mg/kg dose, the following visits will be performed: Visit 8, Visit 9, Visit 10, 
Visit 11, Visit 12, Visit 13, Visit 14, and Visit 15, corresponding to UCB7665 7mg/kg Visit 6, 
Visit 7, Visit 8, Visit 9, Visit 10, Visit 11, Visit 12, and Visit 13.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 234 of 353
Has been changed to:
Section 8.4
Observation Period
For UCB7665 4mg/kg weekly dose (Dose Arm 1), the following visits will be performed: 
Visit 8, Visit 9, Visit 10, Visit 11, Visit 12, Visit 13, Visit 14, and Visit 15, corresponding to 
UCB7665 7mg/kg weekly dose (Dose Arm 2) on Visit 6, Visit 7, Visit 8, Visit 9, Visit 10, 
Visit 11, Visit 12, and Visit 13.
For the UCB7665 4mg/kg twice weekly dose (Dose Arm 3), the following visits will be 
performed: Visit 7, Visit 8, Visit 9, Visit 10, Visit 11, Visit 12, Visit 13, and Visit 14.
Change #44
Section 8.3.1 Visit 8 (Week 5/Day 32) [UCB7665 4mg/kg]/ Visit 6 (Week 3/Day 18) 
[UCB7665 7mg/kg]
Has been changed to:
Section 8.4.1 Visit 8 (Week 5/Day 32) [UCB7665 4mg/kg weekly]/ Visit 6 (Week 3/Day 18) 
[UCB7665 7mg/kg weekly]/ Visit 7 (Week 3/Day 18) [UCB7665 4mg/kg twice weekly]
Change #45
Section 8.3.2 Visit 9 (Week 6/Day 36) [UCB7665 4mg/kg]/ Visit 7 (Week 4/Day 22) 
[UCB7665 7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit.
The following assessments will be performed at this visit:
…
Has been changed to:
Section 8.4.2 Visit 9 (Week 6/Day 36) [UCB7665 4mg/kg weekly]/ Visit 7 (Week 4/Day 22)
[UCB7665 7mg/kg weekly]/ Visit 8 (Week 4/Day 22) [UCB7665 4mg/kg twice weekly]
This is the second visit in the Observation Period. A visit window of ±2 days is applicable for 
this visit relative to the day of the final dosing visit. The following assessments will be 
performed at this visit:
…
Change #46
Section 8.3.3 Visit 10 (Week 7/Day 43) [UCB7665 4mg/kg]/ Visit 8 (Week 5/Day 29)
[UCB7665 7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
This visit can be performed at home with a healthcare professional visiting the subject at his/her 
home. The following assessments will be performed at this visit:
…
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 235 of 353
Has been changed to:
Section 8.4.3 Visit 10 (Week 7/Day 43) [UCB7665 4mg/kg weekly]/ 
Visit 8 (Week 5/Day 29) [UCB7665 7mg/kg weekly]/ 
Visit 9 (Week 5/Day 29) [UCB7665 4mg/kg twice weekly]
This is the third visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visit:
…
Change #47
Section 8.3.4 Visit 11 (Week 8/Day 50) [UCB7665 4mg/kg]/ Visit 9 (Week 6/Day 36)
[UCB7665 7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit.
The following assessments will be performed at this visit:
…
Has been changed to:
Section 8.4.4 Visit 11 (Week 8/Day 50) [UCB7665 4mg/kg weekly]/ Visit 9 (Week 6/Day 36)
[UCB7665 7mg/kg weekly]/ Visit 10 (Week 6/Day 36) [UCB7665 4mg/kg twice weekly]
This is the fourth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. The following assessments will be performed at 
this visit:
…
Change #48
Section 8.3.5 Visit 12 (Week 9/Day 57) [UCB7665 4mg/kg]/ Visit 10 (Week 7/Day 43)
[UCB7665 7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
This visit can be performed at home with a healthcare professional visiting the subject at his/her 
home. The following assessments will be performed at this visit:
…
Has been changed to:
Section 8.4.5 Visit 12 (Week 9/Day 57) [UCB7665 4mg/kg weekly]/ Visit 10 (Week 7/Day 43) 
[UCB7665 7mg/kg weekly]/ Visit 11 (Week 7/Day 43) [UCB7665 4mg/kg twice weekly]
This is the fifth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visit:
…
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 236 of 353
Change #49
Section 8.3.6 Visit 13 (Week 10/Day 64) [UCB7665 4mg/kg]/ Visit 11 (Week 8/Day 50)
[UCB7665 7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit.
The following assessments will be performed at this visit:
…
Has been changed to:
Section 8.4.6 Visit 13 (Week 10/Day 64) [UCB7665 4mg/kg weekly]/Visit 11 (Week 8/Day 50) 
[UCB7665 7mg/kg weekly]/ Visit 12 (Week 8/Day 50) [UCB7665 4mg/kg twice weekly]
This is the sixth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. The following assessments will be performed at 
this visit:
…
Change #50
Section 8.3.7 Visit 14 (Week 11/Day 71) [UCB7665 4mg/kg weekly]/Visit 12 (Week 9/Day 57) 
[UCB7665 7mg/kg weekly]/ Visit 13 (Week 9/Day 57) [UCB7665 4mg/kg twice weekly]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
This visit can be performed at home with a healthcare professional visiting the subject at his/her 
home. The following assessments will be performed at this visit:
…
Has been changed to:
Section 8.4.7 Visit 14 (Week 11/Day 71) [UCB7665 4mg/kg weekly]/Visit 12 (Week 9/Day 57)
[UCB7665 7mg/kg weekly]/ Visit 13 (Week 9/Day 57) [UCB7665 4mg/kg twice weekly]
This is the seventh visit in the Observation Period. A visit window of ±2 days is applicable for 
this visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visit:
…
Change #51
Section 8.3.8 End-of-Study Visit: Visit 15 (Week 13/Day 85) [UCB7665 4mg/kg]/ 
Visit 13 (Week 11/Day 71) [UCB7665 7mg/kg]
Has been changed to:
Section 8.4.8 End-of-Study Visit: Visit 15 (Week 13/Day 85) [UCB7665 4mg/kg weekly]/ 
Visit 13 (Week 11/Day 71) [UCB7665 7mg/kg weekly]/ Visit 14 (Week 11/Day 71)
[UCB7665 4mg/kg twice weekly]
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 237 of 353
NEW bullet:

For all dose arms, collection of whole blood for exploratory RNA analyses
Change #52
Section 8.4
Early Withdrawal Visit
Paragraph #3:
The assessments to be done at both the Early Withdrawal Visit as well as the End-of-Study Visit 
are the same as those at Visit 15 for the UCB7665 4mg/kg group or Visit 13 for the 
UCB7665 7mg/kg group, except for the subject exit interview which will be performed at the 
End-of-Study Visit only.
Has been changed to:
Section 8.5
Early Withdrawal Visit
The assessments to be done at both the Early Withdrawal Visit as well as the End-of-Study Visit 
are the same as those at Visit 15 for the UCB7665 4mg/kg weekly (Dose Arm 1) group, Visit 13 
for the UCB7665 7mg/kg weekly (Dose Arm 2) group, or Visit 14 for the UCB7665 4mg/kg 
twice weekly (Dose Arm 3) group, except for the subject exit interview which will be performed 
at the End-of-Study Visit only.
Change #53
Section 9.1
Platelet counts
NEW variables:

Baseline-corrected AUEC for platelet count calculated from Baseline to the end of study visit

Clinical Response: platelet count ≥30x109/L and <100x109/L with at least 2-fold increase 
from Baseline value and absence of bleeding

Time to Clinical Response: time from starting treatment to achievement of Clinical Response

Duration of Clinical Response: measured from achievement of Clinical Response to loss of 
Clinical Response (loss of Clinical Response defined as platelet count <30x109/L or less than 
2-fold increase from Baseline platelet count or presence of bleeding)

Complete Clinical Response: platelet count ≥100x109/L and absence of bleeding

Time to Complete Clinical Response: time from starting treatment to achievement of 
Complete Clinical Response

Duration of Complete Clinical Response: measured from achievement of Complete Clinical 
Response to loss of Complete Clinical Response (loss of Complete Clinical Response defined 
as platelet count <100x109/L or presence of bleeding)

No Clinical Response: platelet count <30x109/L and less than 2-fold increase from Baseline 
or presence of bleeding
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 238 of 353
Change #54
Section 11
Assessment of other immunological variables
NEW assessment:

Lymphocyte counts (B and T)
Change #55
Section 12.1.1 Definition of adverse event
Paragraph #4:
Bleeding events should not be reported as an AE since these events will be assessed and reported 
during the ITP-BAT assessment. Common Terminology Criteria for Adverse Events (CTCAE) 
grade 3 or more bleeding events should be reported as AEs.
Has been changed to:
Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2 bleeding events 
should not be reported as an AE since these events will be assessed and reported during the 
ITP-BAT assessment; CTCAE grade 3 or more bleeding events should be reported as AEs. 
Change #56
Section 12.1.9
Safety signal detection
Paragraph #1:
The safety variables and ADA results available after 7 days of the final dose of 3 and 6 subjects 
in the UCB7665 4mg/kg dose arm will be reviewed by a DMC (interim analysis 1 and 2) 
comprising at least 1 external expert, the UCB study physician, the UCB DS representative, and 
a biostatistician and will be summarized on an ongoing basis during the study so as to 
continuously evaluate the safety of subjects. The DMC will meet and reach a decision on 
whether or not the study can continue as planned, and whether or not the next dose arm can be 
started. Subsequently, safety variables and ADA results available after 7 days of the final dose of 
3 and 6 subjects in the UCB7665 7mg/kg dose arm (together with all available data from the 
UCB7665 4 mg/kg dose arm) will be reviewed by the DMC (interim analysis 3 and 4).
Has been changed to:
The safety variables and ADA results available after 7 days of the final dose of 3 and 6 subjects 
in the UCB7665 4mg/kg weekly group (Dose Arm 1) will be reviewed by the DMC (interim 
analysis 1 and 2) comprising at least 1 external expert, the UCB study physician, the UCB PS
representative, and a biostatistician and will be summarized on an ongoing basis during the study 
so as to continuously evaluate the safety of subjects. The DMC will meet and reach a decision on 
whether or not the study can continue as planned, and whether or not Dose Arm 2 can be started. 
Subsequently, safety variables and ADA results available after 7 days of the final dose of 3 and 
6 subjects in the UCB7665 7mg/kg weekly (Dose Arm 2) (together with all available data from 
Dose Arm 1 and 2) will be reviewed by the DMC (interim analysis 3 and 4).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 239 of 353
Change #57
Section 12.7
Laboratory measurements
Table 12-2 Laboratory measurements
Deletion of: B and T Lymphocyte count
Addition of: γ-globulin
Change #58
Section 12.7.1 Evaluation of PDILI
Table 12-3 Required investigations and follow up for PDILI
Deletion of: ≥8xULN row
Addition of: Hepatology consult required if ALT or AST ≥8xULN to≥5xULN (and ≥2x 
Baseline) row immediate consultation requirements
Change #59
Section 12.8.512-Lead ECG
Paragraph #1:
A standard 12-lead ECG will be performed at visits as specified in the schedule of study
assessments (Section 5.2). Care should be taken to assure proper lead placement and quality 
ECG recordings. Subjects should rest in a supine position in a controlled, calm environment for 
at least 15 minutes prior to the recording and should be motionless during the recording. The 
ECG will be performed in triplicate prior to blood collection for assessment of laboratory
parameters.
Has been changed to:
A standard 12-lead ECG will be performed at visits as specified in the schedule of study
assessments (Section 5.2). Care should be taken to assure proper lead placement and quality 
ECG recordings. Subjects should rest in a supine position in a controlled, calm environment for 
at least 15 minutes prior to the recording and should be motionless during the recording. 
The ECG will be performed in triplicate prior to blood collection for assessment of laboratory
parameters. Three ECGs should be recorded in a time frame of 5 minutes with at least 1 minute 
difference, 1-2 minutes between the ECGs.
Change #60
Section 14.1
Definition of analysis sets
Full Analysis Set (FAS):
The FAS will consist of all subjects who have received at least 1 infusion (full infusion) of IMP 
and, in addition, have a Baseline and at least 1 post-Baseline measurement for platelet count.
The analysis of the PD, efficacy, and immunologic variables will be performed on the FAS. 
Selected outputs may be repeated for the Per Protocol Set (PPS). Further details will be provided 
in the SAP.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 240 of 353
Has been changed to:
The FAS will consist of all subjects who have received at least 1 infusion (full infusion) of IMP 
and, in addition, have a Baseline and at least 1 post-Baseline measurement for platelet count.
The analysis of the PD (excluding total IgG, IgG subclasses, and IgG depletion assay), efficacy, 
and immunologic variables will be performed on the FAS. Selected outputs may be repeated for 
the PD Per Protocol Set (PD-PPS). Further details will be provided in the SAP. 
Change #61
Section 14.1
Definition of analysis sets
NEW analysis set:
Pharmacodynamic Per Protocol Set (PD-PPS)
The PD-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations potentially affecting the serum concentration of total IgG, as confirmed during a 
pre-analysis review of the data prior to database lock.
The PD-PPS will be used for the analysis of the total IgG, IgG subclasses, and IgG depletion 
assay. 
Change #62
Section 14.2
General statistical considerations
All analyses will be performed using SAS® version 9.2 or later (SAS Institute, Cary, NC, USA). 
Continuous variables will be summarized by visit (where applicable) with the statistics including 
the number of subjects (n), mean, standard deviation (SD), median, minimum, and maximum. 
Categorical variables will be summarized by visit (where applicable) with frequency counts and 
percentages. Analyses will be performed by dose arm, unless otherwise stated. In the event that 
the number of infusions in the planned dose arms (3x7mg/kg and 5x4mg/kg) are modified 
following review by the DMC, the data will be summarized based on the actual dose arms 
completing the study. For example, if the 5x4 mg/kg dose arm is modified such that some 
subjects receive only 4 infusions, then the data will be summarized separately for this new dose 
regimen.
Has been changed to:
All analyses will be performed using SAS® version 9.2 or later (SAS Institute, Cary, NC, USA). 
Continuous variables will be summarized by visit (where applicable) with the statistics including 
the number of subjects (n), mean, standard deviation (SD), median, minimum, and maximum. 
Categorical variables will be summarized by visit (where applicable) with frequency counts and 
percentages. Analyses will be performed by dose arm, unless otherwise stated. In the event that 
the number of planned infusions in Dose Arms 1 and 2 (5x4mg/kg and 3x7mg/kg weekly) are 
modified following review by the DMC, the data will be summarized based on the actual dose 
arms completing the study. For example, if the weekly 5x4mg/kg dose arm is modified such that 
some subjects receive only 4 infusions, then the data will be summarized separately for this new 
dose regimen.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 241 of 353
Change #63
Section 14.3.2 Other safety analyses
Paragraph #1 and #2:
The absolute and relative frequencies for subjects with a given TEAE with respect to the 
preferred term according to the latest available version of the MedDRA, as well as the absolute 
frequencies of the individual TEAEs that have occurred, will be determined within each system 
organ class. Additional tables will summarize TEAEs by maximum intensity and causal 
relationship with UCB7665, as judged by the investigator. Adverse events will be categorized by
severity according to the CTCAE version 4.03 grading. In case the CTCAE grading is not 
available, the intensity (mild/moderate/severe) will be utilized. The TEAEs leading to 
discontinuation of IMP and treatment-emergent SAEs will also be summarized. The action taken, 
time of onset relative to dosing, and duration of each AE will be listed only.
For the continuous laboratory variables, the values and changes from Baseline will be 
summarized at each time point. For categorized values according to the reference range, shift 
tables from Baseline to each post-Baseline time point will be presented for selected variables to 
be defined in the SAP. Values outside the reference range will be flagged in the data listings.
Has been changed to:
The absolute and relative frequencies for subjects with a given TEAE with respect to the 
preferred term according to the latest available version of the MedDRA, as well as the absolute 
frequencies of the individual TEAEs that have occurred, will be determined within each system 
organ class. Additional tables will summarize TEAEs by maximum intensity and causal 
relationship with UCB7665, as judged by the investigator. Adverse events will be categorized by
severity according to the CTCAE version 4.03 grading. In case the CTCAE grading is not 
available, the intensity (mild/moderate/severe) will be utilized. For the purpose of the tabulations 
CTCAE grades will be aligned with the intensity classifications (mild/moderate/severe) to enable 
pooling of the AEs in the summaries. The TEAEs leading to discontinuation of IMP and 
treatment-emergent SAEs will also be summarized. The action taken, time of onset relative to 
dosing, and duration of each AE will be listed only.
For the continuous laboratory variables, the values and changes from Baseline will be 
summarized at each time point. For categorized values according to the reference range, shift 
tables from Baseline to each post-Baseline time point will be presented for selected variables to
be defined in the SAP. Values outside the reference range will be flagged in the data listings. The 
number and percentage of subjects with markedly abnormal laboratory results (based on CTCAE 
grading) will be tabulated for each dose arm.
Change #64
Section 14.4.1 Efficacy analyses
The main efficacy variable is the maximum increase from Baseline in platelet count during the 
study. The maximum increase from Baseline and maximum platelet count during the study will 
be summarized by dose arm.
In addition, all measurements of platelet count will be summarized by dose arm and time point 
using descriptive statistics (including changes from Baseline).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 242 of 353
For each dose arm a 1-sided t-test will be applied to assess if the average maximum increase 
from Baseline is greater than zero. In case the assumptions for the-t-test are not fulfilled a 
variance-stabilizing transformation may be applied in addition and/or an alternative 
nonparametric method may be considered. Further details will be provided in the SAP.
The Response rate, Complete Response rates, and platelet count ≥50x109/L rate will be 
summarized (number of subjects and percentages) and presented with 90% 2-sided confidence 
intervals for the rate of responders at each time point and overall (across all time points).
Response and Complete Response are defined in Section 4.2.
Time to Response, time to Complete Response, time to platelet count ≥50x109/L, duration of 
Response, duration of Complete Response, and duration of platelet count ≥50x109/L will be 
calculated and summarized by dose arm.
The results from the ITP bleeding scale will be summarized at each time point and will include 
the grades for each of the 3 major domains: skin (S), visible mucosae (M), and organs (O).
Results of the NFI-MS will be summarized at each time point, using summary scores where 
applicable. Changes from Baseline will be calculated and summarized.
Has been changed to:
The main efficacy variable is the maximum increase from Baseline in platelet count during the 
study. The maximum increase from Baseline and maximum platelet count during the study will 
be summarized by dose arm.
In addition, all measurements of platelet count will be summarized by dose arm and time point 
using descriptive statistics (including changes from Baseline).
For Dose Arm 1 and 2, a 1-sided t-test will be applied to assess if the average maximum increase 
from Baseline is greater than zero. In case the assumptions for the-t-test are not fulfilled, an 
alternative nonparametric method may be considered. Further details will be provided in the 
SAP.
The Response, Complete Response, and platelet count ≥50x109/L will be summarized (number 
of subjects and percentages) and presented with 90% 2-sided confidence intervals for the rate of 
responders at each time point and overall (across all time points). Response and Complete 
Response are defined in Section 4.2. The analysis will be repeated for the Clinical Response 
variables defined in Section 4.2.
Time to Response, time to Complete Response, time to platelet count ≥50x109/L, duration of 
Response, duration of Complete Response, duration of platelet count ≥50x109/L, and 
Baseline-corrected AUEC for platelet count will be calculated and summarized by dose arm. The 
time to first response will be analyzed using a log-rank test and displayed using Kaplan-Meier 
curves. The time taken Response, time to Complete Response, and respective durations will be 
summarized by dose arm.
The results from the ITP bleeding scale will be summarized at each time point and will include 
the grades for each of the 3 major domains: skin (S), visible mucosae (M), and organs (O). In 
addition the number and percentage of subjects with severe or clinically relevant bleeding and 
number and percentage of subjects with absence of bleeding will be summarized at each time 
point.
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Results of the NFI-MS will be summarized at each time point, using summary scores where 
applicable. Changes from Baseline will be calculated and summarized.
Additional subgroup analyses may be performed as needed and further details will be provided in 
SAP regarding these analyses.
Change #65
Section 14.4.3 Pharmacodynamic analyses
For all PD variables, descriptive statistics for the values and change from Baseline and/or 
percentage change from Baseline will be tabulated by time point. If appropriate, measurements 
will be log-transformed.
The PD variables will include ITP-specific autoantibodies
total IgG, and IgG subclasses. In addition, for total IgG, the maximum decrease from Baseline 
and minimum value will be evaluated and summarized. Figures of mean values over time and 
changes from Baseline will be presented.
Has been changed to:
For all PD variables, descriptive statistics for the values and change from Baseline and/or 
percentage change from Baseline will be tabulated by time point. 
The PD variables will include ITP-specific autoantibodies
total IgG, IgG subclasses, and total and endogenous IgG measured via IgG depletion assay. In 
addition, for total IgG, the maximum decrease from Baseline and minimum value will be 
evaluated and summarized. Figures of mean values over time and changes from Baseline will be 
presented.
Change #66
Section 14.4.4 Immunologic variables
Paragraphs #1 and #2:
All immunologic variables including concentrations of immunoglobulins (IgA, IgE, and IgM),
serum (C3 and C4) and plasma (C3a and C5a) complement levels, serum biomarkers 
 
 serum BAFF levels and the results of 
the IgG depletion assay will be summarized by dose arm over time (including changes from 
Baseline) using descriptive statistics. Figures of mean values over time and changes from 
Baseline may be presented.
The ADA status (negative/positive) and changes in relative mass units from Baseline will be 
summarized by dose arm; figures will also be presented.
Has been changed to:
All immunologic variables including concentrations of immunoglobulins (IgA, IgE, and IgM), 
serum (C3 and C4) and plasma (C3a and C5a) complement levels, serum biomarkers
 
, serum BAFF levels, and lymphocyte 
counts (B and T) will be summarized by dose arm over time (including changes from Baseline) 
using descriptive statistics. Figures of mean values over time and changes from Baseline may be 
presented.
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TP0001
Confidential
Page 244 of 353
The ADA status (negative/positive) will be summarized by dose arm at each visit and overall; 
figures will also be presented in conjunction with PK concentrations of UCB7665 and with IgG 
depletion assay results.
Change #67
Section 14.4.5.2
Subject characteristics
Bullet #3:

Prior and concomitant medications
Has been changed to:

Past, prior, and concomitant medications
Change #68
Section 14.7
Planned interim analysis and data monitoring
Paragraphs #2, #4, #6, #8, and #13:
For the sequential adaptive design in this study, at least 4 interim analyses will be performed. 
Safety data from the interim analyses will be reviewed by the DMC to monitor the safety, to 
adapt the dose regimen, and to decide when and if the UCB7665 7mg/kg dose arm should be 
opened. Planned dosing may be discontinued for all subjects on a dose arm (see Section 6.5).
If the study continues without modifications, the next interim analysis will take place after data 
from 3 additional subjects are available. Based on the available combined data of the first 
6 subjects, the DMC will decide if the 3x7mg/kg dose arm can be initiated. If the new dose arm 
will be initiated and if the 5x4mg/kg will be continued, new subjects will be randomized to 1 of 
the 2 dose arms in an allocation ratio of 1:1(Once 15 subjects are in the 4mg/kg group, the 
remaining subjects will not be randomized. They will be allocated to the 7mg/kg group).
The fourth interim analysis and review of data by DMC will take place after safety data (7 days 
after final dose) is available for the first 6 subjects in Dose Arm 2.
The potential decisions based on the fourth and subsequent interim analysis for the UCB7665 
7mg/kg cohort are in line with the decisions described above for the UCB7665 4mg/kg cohort.
A detailed description of the DMC composition, processes and responsibilities, criteria to 
escalate to the next dose arm, and criteria to stop a dose arm will be provided in a separate DMC 
charter.
Has been changed to:
For the sequential adaptive design in this study, at least 4 interim analyses will be performed. 
Safety data from the interim analyses will be reviewed by the DMC to monitor the safety, to 
adapt the dose regimen, and to decide when and if the UCB7665 7mg/kg weekly group (Dose 
Arm 2) should be opened. Planned dosing may be discontinued for all subjects in a dose arm (see 
Section 6.5).
If the study continues without modifications, the next interim analysis will take place after data 
from 3 additional subjects are available. Based on the available combined data of the first 
6 subjects, the DMC will decide if the 3x7mg/kg dose arm can be initiated. If the new dose arm 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 245 of 353
will be initiated and if the 5x4mg/kg will be continued, new subjects will be randomly assigned
to 1 of the 2 dose arms in an allocation ratio of 1:1.
The fourth planned interim analysis and review of data by DMC will take place after safety data 
(7 days after final dose) is available for the first 6 subjects in Dose Arm 2.
The potential decisions based on the fourth and subsequent interim analysis for the UCB7665 
7mg/kg group (Dose Arm 2) are in line with the decisions described above for the UCB7665 
4mg/kg weekly group (Dose Arm 1).
A detailed description of the DMC composition, processes and responsibilities, criteria to 
escalate to the next dose arm, and criteria to stop, or continue a dose arm will be provided in a 
separate DMC charter.
Change #69
Section 14.8
Determination of sample size
Paragraph #1:
The sample size of 15 subjects, in each dose arm, is mainly based on the efficacy objective of the 
study. In addition the 2x15 subjects ensure that sufficient data are available to form conclusions 
about the safety of administering UCB7665.
Has been changed to:
The sample size of 15 subjects in Dose Arms 1 and 2, is mainly based on the efficacy objective 
of the study. In addition the 15 subjects in Dose Arms 1 and 2 ensure that sufficient data are 
available to form conclusions about the safety of administering UCB7665. Six subjects in Dose 
Arm 3 were judged to be sufficient in order to explore IgG reductions for the 5x4mg/kg/2 weeks 
dose regimen.
Change #70
Section 15.1
Informed consent
NEW paragraph #6:
Subjects have the right to withdraw their consent for the exploratory genomic substudy at any 
point without any impact on their care or participation in the main study. In this case, any data 
already generated on the samples will be retained and used, but no further analysis will occur.
Change #71
Section 15.4
Subject privacy
NEW paragraphs #3 and #4:
Genetic analysis data will not be shared with the subjects and will be subject to the highest level 
of data protection, as per European regulations.
Samples may be shared with collaborators working within UCB and may be analyzed at a third 
party site, but only in relation to the aims of this exploratory analysis as detailed in this study
protocol. Samples may be stored for up to 20 years and maybe used at any time up to that point. 
Samples will remain under the control of UCB at all times and may be destroyed at any point 
before the 20 year expiration date.
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TP0001
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Change #72
Section 17 References
NEW reference:
Johnsen J. Pathogenesis in immune thrombocytopenia: new insights. Hematology Am Soc 
Hematol Educ Program. 2012;2012:306-12.
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15 Feb 2017
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TP0001
Confidential
Page 247 of 353
18.9
Protocol Amendment 3
Rationale for the amendment
The primary purpose of this substantial amendment is to include three additional cohorts and a 
non-mandatory genomic substudy.
The previous protocol amendment (Protocol Amendment 2) was written to introduce a third 
cohort of 4mg/kg sc twice weekly. However, based on preliminary emerging data, it was
expected that the planned inclusion of a 3rd dose arm with 4mg/kg of sc UCB7665 given twice 
per week would not create additional insight regarding the safety and the tolerability of 
UCB7665 in subjects with ITP. Therefore the planned implementation of protocol amendment 
#02 has been canceled. Instead, protocol amendment 3 will enable to further explore the safety, 
tolerability and PD effect of the same cumulative dose of UCB7665 administered with higher 
doses given in less sc infusions by integrating three new dose arms into the study.
Dose Arm 3 (10mg/kg weekly) with a cumulative dose of 20mg/kg will be opened as per DMC 
recommendation after review of the safety data of at least 6 subjects of Dose Arm 2 (7mg/kg 
weekly).
Dose Arm 4 with a single dose of 15mg/kg will be activated after review of the safety data of at 
least 6 subjects of Dose Arm 3 (10mg/kg weekly) and the DMC recommends this 4th dose 
increase.
Dose Arm 5 with a single dose of 20mg/kg will be activated after review of the safety data of at 
least 6 subjects of Dose Arm 4 (15mg/kg weekly) and the DMC recommends this 4th dose 
increase.
During this amendment, additional exploratory genomic (DNA and RNA) analyses have been 
added as an optional substudy to evaluate the genomic components of ITP to understand the 
molecular etiology, progression, and treatment of the disease.
All of the changes that were made in protocol amendment 2 that are still applicable to the current
amendment 3 will be included in this section.
Modifications and changes
Global changes

The following changes were made throughout the protocol:

Addition of a new dose arm 10mg/kg administered once per week, a total of 2 sc doses.

Addition of a new dose arm 15mg/kg administered in one sc dose.

Addition of a new dose arm 20mg/kg administered in one sc dose. 

Additional exploratory genomic analyses added as an optional substudy.

Addition of detailed tuberculosis assessment to ensure the subject safety

Study variables were rearranged into ‘primary and others and exploratory variables.’ 


Serum biomarkers were changed to exploratory safety biomarkers throughout.
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TP0001
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Page 248 of 353

The Clinical Response upper limit of normal (<100x109/L) was deleted.

The IgG depletion assay was removed.

Clarification was added that ECG is done in triplicate.
Specific changes
Change #1
STUDY CONTACT INFORMATION
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Straße 10
40789 Monheim 
GERMANY
Phone:
Fax:
Has been changed to:
Name:
, MD
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporation Drive, Suite 175
Raleigh
NC 27617, USA
Phone:
Fax:
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Clinical Study Protocol
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TP0001
Confidential
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Change #2
Clinical Project Manager
Name:
Address:
UCB Biopharma SPRL
Allée de la Recherche 60
B-1070 Brussels
BELGIUM
Phone:
Fax:
Has been changed to:
Name:
Address:
UCB BioSciences GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
Germany
Phone:
Fax:
Change #3
LIST OF ABBREVIATIONS
ICH
International Conference on Harmonisation
Has been changed to:
ICH
International Council for Harmonisation
Change #4
LIST OF ABBREVIATIONS
The following additions were made to the list of abbreviations:
AUEC
area under the effect curve
DNA
deoxyribonucleic acid
EOS
End of Study
IGRA
interferon-gamma release assay
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LTB
latent tuberculosis
mRNA
messenger ribonucleic acid
miRNA
micro ribonucleic acid
NTMBI
nontuberculosis myobacterial infection
PD-PPS
Pharmacodynamic Per Protocol Set
RNA
ribonucleic acid
TB
tuberculosis
Change #5
LIST OF ABBREVIATIONS
The following abbreviation was deleted:
Change #6
Section 1 SUMMARY
Paragraph #3
TP0001 is a Phase 2, multicenter, open-label, multiple-dose, 2-dose-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 administered as subcutaneous (sc) doses of 4mg/kg 
or 7mg/kg, in subjects ≥18 years of age with persistent (>3 months up to 12 months after 
diagnosis) or chronic (more than 12 months after diagnosis) primary ITP.
Has been changed to:
TP0001 is a Phase 2, multicenter, open-label, multiple-dose, multiple-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 administered as subcutaneous (sc) doses of 4mg/kg, 
7mg/kg, and 10mg/kg, 15mg/kg, and 20mg/kg (resulting in cumulative doses of 20mg/kg, 
21mg/kg, 20mg/kg 15 mg/kg and 20mg/kg respectively), in subjects ≥18 years of age with 
persistent (>3 months up to 12 months after diagnosis) or chronic (more than 12 months after 
diagnosis) primary ITP.
Change #7
Section 1 SUMMARY
Paragraph #4:
The study is planned to be conducted at approximately 25 sites in Europe and Australia. A total 
of 30 subjects are planned to enter the Dosing Period in the study. The maximum study duration 
for study participation for an individual subject is approximately 16 weeks.
Has been changed to:
The study is planned to be conducted at up to approximately 45 sites in Europe and Australia. A 
total of approximately 48 to 66 subjects (dependent on emerging safety data and corresponding 
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Clinical Study Protocol
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TP0001
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Page 251 of 353
DMC recommendation) are planned to enter the Dosing Period in the study. The maximum study
duration for study participation for an individual subject is approximately 16 weeks.
Change #8
Section 1 SUMMARY
Paragraph #5:
The study will evaluate 2 dose arms of UCB7665. Subjects in Dose Arm 1 will receive 5 doses 
of UCB7665 4mg/kg sc at 1 week intervals and subjects in Dose Arm 2 will receive 3 doses of 
UCB7665 7mg/kg sc at 1 week intervals.
Has been changed to:
The study is intended to evaluate 5 dose arms of UCB7665. Subjects in Dose Arm 1 will receive 
5 doses of UCB7665 4mg/kg sc at 1 week intervals, subjects in Dose Arm 2 will receive 3 doses 
of UCB7665 7mg/kg sc at 1 week intervals, subjects in Dose Arm 3 will receive 2 doses of 
UCB7665 10mg/kg sc at 1 week intervals, Dose Arm 4 will receive 1 dose of UCB7665 
15mg/kg sc and Dose Arm 5 will receive 1 dose of UCB7665 20mg/kg sc. 
Change #9
Section 1 SUMMARY
Paragraph #6:
The study consists of a Screening Period (up to 4 weeks), Dosing Period of 2 to 4 weeks, and an 
Observation Period of 8 weeks. The Screening Visit corresponds to Visit 1 of the study. The 
Dosing Period will commence at Visit 2 (Baseline Visit), with dosing visits scheduled at weekly 
intervals. The Observation Period will start after the final dose administration with a visit 
scheduled 3 days after the final dose and weekly thereafter (ie, weekly after final dose) for a 
period of 8 weeks. The End-of-Study Visit will be performed at the end of the Observation 
Period, ie, 8 weeks after the final dose of investigational medicinal product (IMP).
Has been changed to:
The study consists of a Screening Period (up to 4 weeks), Dosing Period of 1 day to 4 weeks, and 
an Observation Period of 8 weeks. The Screening Visit corresponds to Visit 1 of the study. The 
Dosing Period will commence at Visit 2 (Baseline Visit), with dosing visits scheduled at weekly 
intervals for Dose Arms 1, 2 and 3 and only one visit scheduled for Dose Arms 4 and 5. The 
Observation Period will start after the last dose administration (or only dose administration for 
Dose Arms 4 and 5) with a visit scheduled 3 days after the last dose and weekly visits thereafter 
(ie, weekly after last or only dose) for a period of 8 weeks. The End-of-Study Visit will be 
performed at the end of the Observation Period, ie, 8 weeks after the last or only dose of 
investigational medicinal product (IMP).
Change #10
Paragraph #7:
The first 6 subjects will be enrolled in Dose Arm 1 only. While recruitment is ongoing, safety
data for the first 3 subjects up to 7 days after the final dose will be reviewed by a Data 
Monitoring Committee (DMC). During a second DMC meeting, safety data for the first 6 
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Clinical Study Protocol
UCB7665
TP0001
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subjects up to 7 days after the final dose will be reviewed. Following this review, the DMC will 
make a decision on whether to open Dose Arm 2 for enrollment. Once the DMC has approved 
initiation of Dose Arm 2, subsequent subjects will be randomized to 1 of the 2 dose arms using 
an interactive voice/web response system (IXRS). The aim is to have 15 subjects in each dose 
arm. The DMC may also decide to reduce the number of doses in each of the dose arms based on 
review of data during the study. Safety data will also be reviewed on an ongoing basis during the 
study so as to continuously evaluate the safety of subjects.
Has been changed to:
The first 6 subjects will be enrolled in Dose Arm 1 only. While recruitment is ongoing, safety
data for the first 3 subjects up to 7 days after the last dose of the third subject will be reviewed by 
the Data Monitoring Committee (DMC). During a second DMC meeting, all available safety 
data up to cut off date defined as 7 days after the last dose of the sixth subject will be reviewed. 
Following this review, the DMC will make a recommendation on whether to open Dose Arm 2 
for enrollment. Once the DMC has advocated the initiation of Dose Arm 2, the subsequent 
subjects for the first 2 arms will be randomly assigned in 1:1 ratio to either Dose Arm 1 or Dose 
Arm 2 using an interactive voice/web response system (IXRS). Once 15 subjects are enrolled in 
Dose Arm 1, the subsequently enrolled subjects will be enrolled in Dose Arm 2.
Change #11
Paragraph #8 modified and NEW paragraphs #9 and #10 added:
After the safety data review of at least 6 subjects in Dose Arm 2 is done, the DMC will make a 
recommendation on whether to open Dose Arm 3 for enrollment. Once the DMC has advocated 
the initiation of Dose Arm 3 and the enrollment of 15 subjects in Dose Arm 2 has been 
completed, the subsequent subjects will be assigned to Dose Arm 3 only. After every third 
subject has been enrolled, DMC will review all available safety data up to cut off date defined as 
7 days after the last dose. Depending on the emerging safety data of 6 subjects in Dose Arm 3,
the DMC will recommend whether to open Dose Arm 4 for enrollment or to include additional 
subjects in Dose Arm 3. If applicable, this step is planned to be done stepwise in groups of 3 
subjects. A maximum of 12 subjects are planned for Dose Arm 3. The DMC will recommend to 
open Dose Arm 4 for enrollment in a subsequent DMC meeting, if applicable.
Once the DMC has advocated the initiation of Dose Arm 4, the enrollment of Dose Arm 3 will 
be closed and all subsequently enrolled subjects will be assigned to Dose Arm 4. After every
third subject that has been enrolled, DMC will review all available safety data up to cut off date 
defined as 7 days after the dosing of the third subject in Dose Arm 3. Depending on the emerging 
safety data of 6 subjects in Dose Arm 4, the DMC will recommend whether to open Dose Arm 5 
for enrollment or to include additional subjects in Dose Arm 4. If applicable, this step is planned 
to be done stepwise in groups of 3 subjects. A maximum of 12 subjects are planned for Dose 
Arm 4. The DMC will recommend to open Dose Arm 5 for enrollment in a subsequent meeting, 
if applicable.
Once the DMC has advocated the initiation of Dose Arm 5, the enrollment of Dose Arm 4 will 
be closed and the subsequently enrolled subjects will be assigned to Dose Arm 5. After every
third subject is enrolled, the DMC will review all available safety data up to the cutoff date 
defined as 7 days after the dosing of the third subject in Dose Arm 4. Depending on the emerging 
safety data of 6 subjects in Dose Arm 5, the DMC will recommend to include additional subjects 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 253 of 353
in Dose Arm 5. If applicable, this step is planned to be done stepwise in groups of 3. A 
maximum of 12 subjects are planned for Dose Arm 5.
The DMC may also decide to reduce the number of doses in each of the dose arms, to stop a dose 
arm or not to open a dose arm based on review of safety data during the study. Safety data will 
also be reviewed on an ongoing basis by CRO medical monitor and UCB physician during the 
study so as to continuously evaluate the safety of subjects.
Change #12
Section 1 SUMMARY
Paragraph #12:
The following efficacy variables will be assessed: Response (platelet count ≥30x109/L and at 
least 2-fold increase of the Baseline count) during the study and by visit; Complete Response 
(platelet count ≥100x109/L) during the study and by visit; platelet count ≥50x109/L during the 
study and by visit; the maximum value and maximum increase from Baseline in platelet count 
during the study; value and change from Baseline in platelet count over time; time to Response 
(time from starting treatment to achievement of Response); time to Complete Response (time 
from starting treatment to achievement of Complete Response); time to achieving platelet count 
≥50x109/L; duration of Response (measured from achievement of Response to loss of Response 
[defined as platelet count below 30x109/L or less than 2-fold increase of Baseline platelet 
count]); duration of Complete Response (measured from achievement of Complete Response to 
loss of Complete Response [defined as platelet count below 100x109/L]); duration of platelet 
count ≥50x109/L (measured from achievement of platelet count ≥50x109/L to reduction of 
platelet count below 50x109/L); ITP bleeding score over time; and Patient Reported Outcome 
(PRO), ie, Neurological Fatigue Index for Multiple Sclerosis (NFI-MS) summary score over 
time. Plasma concentration of UCB7665 over time will be assessed as the PK variable. The PD 
variables are minimum value and maximum decrease in total IgG concentration during the study;
IgG subclass concentrations; and ITP-specific autoantibody
in serum over time. Other immunological variables to be evaluated are total IgA, IgE, and IgM 
levels; serum (C3 and C4) and plasma (C3a and C5a) complement levels; ADA status 
(negative/positive) and relative mass units; serum biomarkers 
B cell activating factor (BAFF) levels and the results of the IgG depletion assay; and cytokines 
(for subjects experiencing infusion reactions). Additional exploratory biomarkers may be 
investigated if needed using the samples already available.
Has been changed to:
Now paragraph #13:
The following efficacy variables will be assessed: Response (platelet count ≥30x109/L and at 
least 2-fold increase of the Baseline count) during the study and by visit; Complete Response 
(platelet count ≥100x109/L) during the study and by visit; platelet count ≥50x109/L during the 
study and by visit; the maximum value and maximum increase from Baseline in platelet count 
during the study; value and change from Baseline in platelet count over time; Baseline-corrected 
area under the effect curve (AUEC) for platelet count; time to Response (time from starting 
treatment to achievement of Response); time to Complete Response (time from starting treatment 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 254 of 353
to achievement of Complete Response); time to achieving platelet count ≥50x109/L; duration of 
Response (measured from achievement of Response to loss of Response [defined as platelet 
count below 30x109/L or less than 2-fold increase of Baseline platelet count]); duration of 
Complete Response (measured from achievement of Complete Response to loss of Complete 
Response [defined as platelet count below 100x109/L]); duration of platelet count ≥50x109/L
(measured from achievement of platelet count ≥50x109/L to reduction of platelet count below 
50x109/L); Clinical Response (defined as platelet count ≥30x109/L with at least 2-fold increase 
from Baseline value and absence of bleeding); time to Clinical Response (time from starting 
treatment to achievement of Clinical Response); duration of Clinical Response (measured from 
achievement of Clinical Response to loss of Clinical Response [loss of Clinical Response 
defined as platelet count <30x109/L or less than 2-fold increase from Baseline platelet count or 
presence of bleeding]); Complete Clinical Response (defined as platelet count ≥100x109/L and 
absence of bleeding); time to Complete Clinical Response (time from starting treatment to 
achievement of Complete Clinical Response); duration of Complete Clinical Response 
(measured from achievement of Complete Clinical Response to loss of Complete Clinical 
Response [loss of Complete Clinical Response defined as platelet count <100x109/L or presence 
of bleeding]); no Clinical Response (defined as platelet count <30x109/L and less than 2-fold 
increase from Baseline or presence of bleeding); ITP bleeding score over time; and Patient 
Reported Outcome (PRO), ie, Neurological Fatigue Index for Multiple Sclerosis (NFI-MS) 
summary score over time. Plasma concentration of UCB7665 over time will be assessed as the 
PK variable. The PD variables are minimum value and maximum decrease in total IgG 
concentration during the study; IgG subclass concentrations; and ITP-specific autoantibody 
 in serum over time. Other immunological variables to be 
evaluated are total IgA, IgE, and IgM levels; serum (C3 and C4) and plasma (C3a and C5a) 
complement levels; ADA status (negative/positive) and relative mass units; exploratory safety 
biomarkers 
 and B cell activating factor 
(BAFF) levels; B and T lymphocytes; and cytokines (for subjects experiencing infusion 
reactions).
Change #13
Section 1 SUMMARY
Exploratory genomic analyses substudy details are added as follows:
During this study, subjects will also have the option of providing additional informed consent for 
exploratory deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) (ie, messenger RNA 
[mRNA] and micro RNA [miRNA]) analyses. Participation in this additional portion of the study
is optional and does not preclude subject’s eligibility for participation in the main study. The 
additional genomic samples must not be collected if the subject has not consented to participate 
in this exploratory genomic substudy.
Change #14
Section 1 SUMMARY
New paragraph added at the end of the summary:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 255 of 353
Prior to this amendment, a protocol amendment 2 with a dose arm 4mg/kg twice weekly was 
planned, however the corresponding protocol amendment 2 was not implemented. These changes 
are highlighted in Section 18.8.
Change #15
Section 1 INTRODUCTION
Paragraph #11:
In 4-week and 13-week toxicity studies with 8-week, treatment-free recovery periods in 
Cynomolgus monkeys, UCB7665 induced the expected large decreases (75% to 90%) in plasma 
IgG in all animals which was maintained for the duration of both studies in the majority of the 
animals, with only minor effects on albumin levels. UCB7665 was well tolerated at the highest 
dose levels tested of UCB7665 150mg/kg sc and UCB7665 150mg/kg iv administered every
3 days (the no observed adverse effect level [NOAEL]).
Has been changed to:
In 4-week and 13-week toxicity studies with 8-week, treatment-free recovery periods in 
Cynomolgus monkeys, UCB7665 induced the expected large decreases (75% to 90%) in plasma 
IgG in all animals which was maintained for the duration of both studies in the majority of the 
animals, with only minor effects on albumin levels. UCB7665 was well tolerated at the highest 
dose levels tested of UCB7665 150mg/kg sc and UCB7665 150mg/kg iv administered every
3 days (there was no observed adverse effect level [NOAEL]).
Change #16
Section 1 INTRODUCTION
Paragraph #12:
Further information on the PK, PD, and safety profiles for UCB7665 from nonclinical studies, 
and preliminary safety information from clinical studies, can be obtained from the current 
version of the UCB7665 Investigator’s Brochure.
Has been changed to:
Further information on the PK, PD, and safety profiles for UCB7665 from nonclinical studies, 
and preliminary safety information from clinical studies (including data from this study), can be 
obtained from the current version of the UCB7665 Investigator’s Brochure.
Change #17
Section 1 INTRODUCTION
Paragraph #13:
Exploratory genomic analyses substudy details are added as follows:
Subjects will also have the option of providing additional informed consent for exploratory DNA 
and RNA (mRNA and miRNA) analyses as described in Section 5.1.1.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 256 of 353
Change #18
Section 3.3
Exploratory objectives
Two additional NEW bullets:

To evaluate the genomic components of ITP to understand the molecular etiology, 
progression, and treatment of the disease, applicable only for subjects consenting to 
participate in the optional genomic analyses substudy. 

Change #19
Section 4 Study Variables sub-sections were renumbered
4.1
Safety variables 
4.1.1. Primary safety variables 
4.1.2
Other saftey variables 
4.2
Efficacy variables 
4.3
Pharmacokinetic and pharmacodynamic variables
4.3.1
Pharmacokinetic variable
4.3.2
Pharmacodynamic variables
4.4
Other immunological variables
Has been changed to:
4.1 Primary variable
4.2 Others and exploratory variables 
4.2.1
Safety variables 
4.2.2
Efficacy variables 
4.2.3
Pharmacokinetic variables 
4.2.4
Pharmacodynamic variables 
4.2.5
Other immunological variables 
Change #20
Section 4.2.2 Efficacy variables
Additional efficacy variables listed as follows:

Baseline-corrected AUEC for platelet count

Clinical Response: platelet count ≥30x109/L with at least 2-fold increase from Baseline value 
and absence of bleeding
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 257 of 353

Time to Clinical Response: time from starting treatment to achievement of Clinical Response

Duration of Clinical Response: measured from achievement of Clinical Response to loss of 
Clinical Response (loss of Clinical Response defined as platelet count <30x109/L or less than 
2-fold increase from Baseline platelet count or presence of bleeding)

Complete Clinical Response: platelet count ≥100x109/L and absence of bleeding

Time to Complete Clinical Response: time from starting treatment to achievement of 
Complete Clinical Response

Duration of Complete Clinical Response: measured from achievement of Complete Clinical 
Response to loss of Complete Clinical Response (loss of Complete Clinical Response defined 
as platelet count <100x109/L or presence of bleeding)

No Clinical Response: platelet count <30x109/L or less than 2-fold increase from Baseline or 
presence of bleeding
Change #21
Section 4.3.2
Pharmacodynamic variables (now Section 4.2.4)
The following variable was deleted:

The value and change from Baseline in endogenous IgG concentrations will be measured by
IgG depletion assay
Change #22
Section 4.3.2 Pharmacodynamic variables (now Section 4.2.4)

Change from Baseline in serum biomarkers 
over time
Has been changed to:
Now moved to Section 4.2.1 Safety variables:

Change from Baseline in exploratory safety biomarkers over time
Change #23
Section 4.4
Other immunological variables (now Section 4.2.5)

Change from Baseline in serum biomarkers 
 over time
Has been changed to:

Change from Baseline in exploratory biomarkers relating to mechanism of action, disease 
activity, treatment response, and clinical outcome
Change #24
Section 4.4
Other immunological variables (now Section 4.2.5)
Additional immunological variable listed as follows:

Lymphocyte counts (B and T)
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 258 of 353
Change #25
Section 4.2.5
Other immunological variables
The following text was deleted:
Cytokine samples will be taken at Baseline for all subjects and at subsequent visits only if the 
subject experiences infusion reactions.
Change #26
Section 5.1
Study description
Paragraphs #1, #2 and #3:
This is a Phase 2, multicenter, open-label, multiple-dose, 2-dose-arm study to evaluate the safety, 
tolerability, and efficacy of UCB7665 in subjects with primary persistent or chronic ITP.
Dose Arm 1: UCB7665 4mg/kg sc (5 doses at an interval of 1 week)
Dose Arm 2: UCB7665 7mg/kg sc (3 doses at an interval of 1 week)
The DMC will monitor emergent safety data during the study. Refer to Section 14.7 for details. 
The maximum duration of the study per subject is approximately 16 weeks, consisting of a 
Screening Period (1 to 28 days), a Dosing Period of 2 or 4 weeks, and an Observation Period of 
8 weeks.
Has been changed to:
This is a Phase 2, multicenter, open-label, multiple-dose, multiple-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 in subjects with primary persistent or chronic ITP.
Dose Arm 1 (15 subjects): UCB7665 4mg/kg sc (5 doses at an interval of 1 week)
Dose Arm 2 (15 subjects): UCB7665 7mg/kg sc (3 doses at an interval of 1 week)
Dose Arm 3 (6 to 12 subjects): UCB7665 10mg/kg sc (2 doses at an interval of 1 week)
Dose Arm 4 (6 to 12 subjects): UCB7665 15mg/kg sc (1 dose)
Dose Arm 5 (6 to 12 subjects): UCB7665 20mg/kg sc (1 dose)
The maximum duration of the study per subject is approximately 16 weeks, consisting of a 
Screening Period (1 to 28 days), a Dosing Period of 1 to 4 weeks, and an Observation Period of 
8 weeks.
Change #27

Section 5.1
Study description
Paragraph #5:
Dosing Period: The first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in 
the Dose Arm 1 will not be randomized. While recruitment is still ongoing, safety data for the 
first 3 subjects up to 7 days after the final dose of the third subject will be reviewed by the DMC. 
During a second DMC meeting, all available safety data up to cut off date defined as 7 days after 
the final dose of the sixth subject will be reviewed. During these reviews recruitment in the dose 
arm will not be stopped. Following this review, the DMC will make a decision on whether to 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 259 of 353
open Dose Arm 2 for enrollment. Once the DMC has approved opening of Dose Arm 2 for 
enrollment, subjects will subsequently be randomized to 1 of the 2 dose arms using IXRS. If the 
new dose arm will be initiated and if the UCB7665 4mg/kg arm will be continued, new subjects 
will be randomized to 1 of the 2 dose arms in an allocation ratio of 1:1 (Once 15 subjects are in 
the 4mg/kg group, the remaining subjects will not be randomized. They will be allocated to the 
7mg/kg group.).
Has been changed to:
Dosing Period: The first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in 
the Dose Arm 1 will not be randomized. While recruitment is still ongoing, safety data for the 
first 3 subjects up to 7 days after the last dose of the third subject in Dose Arm 1 will be 
reviewed by the DMC. During a second DMC meeting, all available safety data up to cut off date 
defined as 7 days after the last dose of the sixth subject in Dose Arm 1 will be reviewed. During 
these reviews recruitment in the dose arm will not be stopped. Following this review, the DMC 
will make a decision on whether to open Dose Arm 2 for enrollment. Once DMC has advocated 
the initiation of Dose Arm 2, the subsequent subjects will be randomly assigned in 1:1 ratio to 
either Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in the Dose 
Arm 1, the remaining subjects will be enrolled in Dose Arm 2.
After the safety data review of at least 6 subjects in Dose Arm 2 is done, the DMC will make a 
recommendation on whether to open Dose Arm 3 for enrollment. Once the DMC has advocated 
the initiation of Dose Arm 3 and the enrollment of 15 subjects in Dose Arm 2 has been 
completed, the subsequent subjects will be assigned to Dose Arm 3 only. After every third 
subject has been enrolled, the DMC will review all available safety data up to cut off date 
defined as 7 days after the dosing. Depending on the emerging safety data of 6 subjects in Dose 
Arm 3, the DMC will recommend whether to open Dose Arm 4 for enrollment or to include 
additional subjects in Dose Arm 3. If applicable, the latter option will be done stepwise in groups 
of 3 subjects. A maximum, 12 subjects will be enrolled in Dose Arm 3. The DMC will 
recommend to open Dose Arm 4 for enrollment in a subsequent DMC meeting, if applicable.
Once the DMC has advocated the initiation of Dose Arm 4, the enrollment of Dose Arm 3 will 
be closed and all subsequent subjects will be assigned to Dose Arm 4. After every third subject is 
enrolled, the DMC will review all available safety data up to the cutoff date defined as 7 days 
after the dosing. Depending on the emerging safety data of 6 subjects in Dose Arm 4, the DMC 
will recommend to include additional subjects in Dose Arm 4 or not. Subjects will be added 
stepwise in groups of 3, if applicable. A maximum of 12 subjects may be enrolled in Dose 
Arm 4. The DMC will recommend to open Dose Arm 5 for enrollment in a subsequent DMC 
meeting, if applicable.
Once the DMC has advocated the initiation of Dose Arm 5, the enrollment of Dose Arm 4 will 
be closed and all subsequent subjects will be assigned to Dose Arm 5. After every third subject is 
enrolled, the DMC will review all available safety data up to the cutoff date defined as 7 days 
after the dosing. Depending on the emerging safety data of 6 subjects in Dose Arm 5, the DMC 
will recommend to include additional subjects in Dose Arm 5 or not. Subjects will be added 
stepwise in groups of 3, if applicable. A maximum of 12 subjects may be enrolled in Dose 
Arm 5.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 260 of 353
Change #28
Section 5.1
Study description
Paragraph #5:
At least 4 interim analyses will be performed. Based on the interim analysis, the DMC will 
assess the safety of UCB7665, determine whether to initiate the UCB7665 7mg/kg dose arm and 
may decide to adapt the dose regimen. Planned dosing may be discontinued for all subjects on a 
dose arm (see Section 6.5). Refer to Section 14.7 for details.
Has been changed to:
At least 11 interim analyses will be performed. Based on the interim analyses, the DMC will 
assess the safety of UCB7665, determine whether to initiate subsequent dose arms and may
decide to adapt the dose regimen. Planned dosing may be discontinued for all subjects in a dose 
arm (see Section 6.5). Refer to Section 14.7 for details.
Change #29
Paragraph #6:
In case the DMC recommends reducing the number of doses (infusions) for either the 
UCB7665 4mg/kg dose or UCB7665 7mg/kg dose based on review of safety data, then the 
additional dose arms receiving a reduced number of doses will be considered as additional new 
dose arms for the study.
Has been changed to:
In case the DMC recommends reducing the number of doses (infusions) for any of the 
predefined dose arms (as applicable) based on review of safety data, then the additional dose 
arms receiving a reduced number of doses will be considered as additional new dose arms for the 
study.
Change #30
Paragraph #7:
Observation Period: Following the final dose, a visit will be scheduled 3 days postdose and 
weekly thereafter for 8 weeks to collect safety and efficacy data.
Has been changed to:
Observation Period: Following the last dose (or only dose administration for Dose Arms 4 and 
5), a visit will be scheduled 3 days postdose and weekly thereafter for 8 weeks to collect safety
and efficacy data.
Change #31
NEW Section 5.1.1
Exploratory genomic analyses
During this study, subjects will also have the option of providing additional informed consent for 
exploratory DNA and RNA analyses. Participation in this additional portion of the study is 
optional and does not preclude subject’s eligibility for participation in the main study. The 
additional genomic samples must not be collected if the subject has not consented to participate 
in this exploratory genomic substudy.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 261 of 353
Once subject provides consent, through a separate informed consent form, blood samples will be 
drawn as follows:
For DNA: Blood samples will be collected at Baseline (Visit 2) for all dose arms. Subsequent 
blood sample will be collected prior to the last dose (ie, Visit 7 for Dose Arm 1, Visit 5 for Dose 
Arm 2, and Visit 4 for Dose Arm 3).
For RNA: Blood samples will be collected at the following time points for different dose arms: 

Dose Arm 1: Baseline (Visit 2), 3 days after dose 1 (Visit 3), prior to the last dose (Visit 7), 
and End of Study Visit (Visit 15).

Dose Arm 2: Baseline (Visit 2), 3 days after dose 1 (Visit 3), prior to the last dose (Visit 5), 
and End of Study Visit (Visit 13). 

Dose Arm 3: Baseline (Visit 2), 3 days after dose 1 (Visit 3), prior to the last dose (Visit 4), 
and End of Study Visit (Visit 12).

Dose Arm 4: Baseline (Visit 2), 3 days after dosing (Visit 3) and End of Study Visit (Visit 
10).

Dose Arm 5: Baseline (Visit 2), 3 days after dosing (Visit 3) and End of Study Visit (Visit 
10). 
For each DNA blood sample a volume of 6mL whole blood is needed and for each RNA sample 
a volume of 2.5mL whole blood is needed.
Failure to provide consent to participate in this substudy will not impact subject’s eligibility to 
participate in the main study.
Any exploratory biomarker or genomic analysis will only ever be related to the exploration of 
the underlying causes of ITP in patients, related biology, and drug response. Justification for 
additional genomic analyses is detailed in Section 5.4.6.
Details on the collection, storage, preparation, and shipping of samples will be presented in the 
Laboratory Manual provided separately.
Any results from this analysis will be reported separately and will not form a part of the main 
clinical study report.
Change #32
Section 5.1.3 Planned number of subjects and sites
A total of 30 subjects are planned to enter the Dosing Period in the study. This number should 
allow for an appropriate assessment of the safety and give information on efficacy of the 
treatment for planning of potential future studies. To achieve the required number of eligible 
subjects to enter the Dosing Period, it is anticipated that 40 subjects will need to be screened. 
These subjects will be enrolled at approximately 25 sites. First subject first visit is planned for 
Q1 2016, last subject last visit for Q3 2017.
Has been changed to:
A total of up to approximately 48 to 66 subjects are planned to enter the Dosing Periods in the 
study (15 subjects in each of Dose Arms 1 and 2, and 6 to 12 subjects in Dose Arms 3, 4, and 5). 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 262 of 353
To achieve the required number of eligible subjects to enter the Dosing Period, it is anticipated 
that approximately 90 subjects will need to be screened. These subjects will be enrolled at 
approximately 45 sites. First subject first visit is planned for Q1 2016, last subject last visit for 
Q2 2018.
Change #33
Section 5.2
Schedule of study assessments
Table 5‒1 presents the tabular scheme of study assessments for UCB7665 4mg/kg dose arm and 
Table 5‒2 presents the tabular scheme of study assessments for UCB7665 7mg/kg dose arm. 
Table 5‒3 presents the assessments to be performed on dosing days.
Has been changed to:
Table 5‒1 presents the tabular scheme of study assessments for the weekly UCB7665 4mg/kg 
dose arm (Dose Arm 1), Table 5‒2 presents the tabular scheme of study assessments for the 
weekly UCB7665 7mg/kg dose arm (Dose Arm 2), Table 5-3 presents the tabular scheme of
study assessments for the weekly UCB7665 10mg/kg dose arm (Dose Arm 3), Table 5-4 presents 
the tabular scheme of study assessments for the one dose of UCB7665 15mg/kg, Table 5-5
presents the tabular scheme of study assessments for the one dose of UCB7665 20mg/kg and 
Table 5‒6 presents the assessments to be performed on dosing days.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 263 of 353
Change #34
Section 5.2
Schedule of study assessments
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consent
X
Demographic data
X
Verification of 
inclusion/exclusion 
criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)f
X
X
X
X
X
Randomizationg
X
Withdrawal criteriah
X
X
X
X
X
X
General 
medical/procedures 
history
X
ITP history
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 264 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
X
X 
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 265 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serology test for HIV, 
hepatitis B, and hepatitis 
C
X
Blood sample for 
cytokines
X
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
X
X
Call to IXRS for treatment 
kit number
X
X
X
X
X
Administration of IMP
X
X
X
X
X
Blood sampling for 
plasma concentration of 
UCB7665
X
X
X
X
X
X
X
X
Anti-UCB7665 
antibodies/IgG depletion 
assay
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 266 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serum complements (C3 
and C4) and plasma
complements (C3a and 
C5a)
X
X
X
X
Serum biomarkers 
 
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum biomarkers 
X
X
X
X
X
X
Serum BAFF levels
X
X
X
X
X
X
X
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
IgA, IgM, IgEl
X
X
X
X
ITP-specific 
autoantibodiesm
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 267 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg dose arm
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Headache questionnairen
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewo
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
; HIV=human immunodeficiency virus;
Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar 
puncture; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
;
a Frequency of assessments on dosing days is detailed in Table 5‒3.  
b Visits 10, 12, and 14 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date.
f Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
g The first 6 subjects will be enrolled in the Dose Arm 1 group only. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the
DMC. Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, subjects subsequently enrolled will 
be randomly assigned subsequently to 1 of the 2 dose arms using an IXRS until 15 subjects are in Dose Arm 1.
h Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
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o


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 268 of 353
i A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
j At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
k Blood sample for cytokines will be obtained only in case of infusion reactions.
l In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 7 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
m
n This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
o A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only. 
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consent
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
X
Platelets for inclusion/withdrawal 
check (local laboratory) f
X
X
X
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This document c
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 269 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Randomizationg
X
Withdrawal criteriah
X
X
X
X
General medical/procedures history
X
ITP history
X
Prior and concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters (hematology, 
chemistry, urinalysis)
Xj
X
X
X
X
X
X
X
X
X
X
X
X
REDACTED COPY 
X
D CO
X
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D C
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DAC
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marketing authorization application and any extensions or variations thereof.
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This document can


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 270 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serology test for HIV, hepatitis B, and 
hepatitis C
X
Blood sample for cytokines
X
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
Call to IXRS for treatment kit number
X
X
X
Administration of IMP
X
X
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
X
X
X
Anti-UCB7665 antibodies/IgG 
depletion assay
X
X
X
X
X
X
X
X
X
X
Serum complements (C3 and C4) and 
plasma complements (C3a and C5a)
X
X
X
X
Serum biomarkers 
 
X
X
X
X
X
X
X
X
X
X
X
Serum biomarkers 
X
X
X
X
REDACTED COPY
C
 
X
E
Xk
D
k
C
D C
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This document cannot be used
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 271 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg dose arm
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serum BAFF levels
X
X
X
X
X
Immunoglobulins (total IgG, IgG 
subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEl
X
X
X
X
ITP-specific autoantibodiesm
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairen
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviewo
X
AE=adverse event; BAFF=B cell activating factor; BL=baseline; CSF=cerebrospinal fluid CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human immunodeficiency virus;
Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar 
puncture; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
a Frequency of assessments on dosing days is detailed in Table 5‒3.
b Visits 8, 10, and 12 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
REDACTED COPY
X
OPY
X
Y 
X
D CO
X
O
D C
TE
AC
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marketing authorization application and any extensions or variations thereof.
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This document c
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days an


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 272 of 353
e The visit windows in the Observation Period are relative to the final dosing visit date. 
f Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate
withdrawal criterion of platelet count >350x109/L.
g The first 6 subjects will be enrolled in the Dose Arm 1 group. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the DMC. 
Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, subjects subsequently enrolled will be 
randomly assigned to one of the dose arms using an IXRS until 15 subjects are in Dose Arm 1.
h Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
i A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
j At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
k Blood sample for cytokines will be obtained only in case of infusion reactions.
l In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 5 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
m
n This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
o A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
TED COPY 
ill be p
OPY
ill be p
y a neu
COP
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r CSF
D C
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REDAC
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ACTE
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pplication and any extensions or variations thereof.
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ons 
e will be
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This document cannot be used to support any marketing autho
ded. In
horiz
ded. In
z


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 273 of 353
Has been changed to:
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of 
inclusion/exclusion 
criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)g
X
X
X
X
X
Randomizationh
X
Withdrawal criteriai
X
X
X
X
X
X
General 
medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
REDACTED COPY 
±2d
OPY
±2dd
Y
d
Y
CO
D C
TE
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DA
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A
used to support any marketing authorization application and any extensions or variations thereof.
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This document cannot 
X
ot
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 274 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationj
X
X
X
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
X
X
X 
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xl
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis 
C
X
IGRA TB testm
X
REDACTED COPY 
X
COP
X
PY
CO
X
TE
X
ED
CT
AC
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any marketing authorization application and any extensions or variations thereof.
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or v
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This document cannot be use
su
se
us
nn
t c


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 275 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
TB signs and symptoms 
questionnaire
X
X
Blood sample for 
cytokines
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Whole blood sample for 
DNA (optional)
X
X
Whole blood sample for 
RNA (optional)
X
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
X
X
Call to IXRS for treatment 
kit number
X
X
X
X
X
Administration of IMP
X
X
X
X
X
Blood sampling for 
plasma concentration of 
UCB7665
X
X
X
X
X
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
X
X
X
X
X
REDACTED COPY 
PY
CO
X
TE
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ED
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support any marketing authorization application and any extensions or variations thereof.
 Period
or v
 Period
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o
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us
no
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 276 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Serum complements (C3 
and C4) and plasma 
complements (C3a and 
C5a)
X
X
X
X
Blood collection for 
exploratory safety 
biomarkers 
X
Xo
X
X
X
X
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Serum BAFF levels
X
X
X
X
X
X
X
Blood collection for 
exploratory biomarker 
analysis
X
X
X
X
X
X
X
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
IgA, IgM, IgEp
X
X
X
X
ITP-specific 
autoantibodies q
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
REDACTED COPY 
PY
AC
CO
X
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AC
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AC
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AC
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This document cann t b
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t c


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 277 of 353
Table 5‒1:
Schedule of assessments for the UCB7665 4mg/kg weekly dose arm (Dose Arm 1)
Assessments
Screening 
Period
Dosing Period 
Observation Period
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Visit
1
2a
3
4a
5a
6a
7a
8
9
10b
11
12b
13
14b
15
BL 
Visit
EOS/ 
EWc
Day
-28 to -1
1
4
8
15
22
29
32
36
43
50
57
64
71
85
Week
1
1
2
3
4
5
5
6
7
8
9
10
11
13
Visit 
Window
±1d
±2dd
±2dd
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Headache questionnairer
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviews
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring; 
DNA=deoxyribonucleic acid; Committee; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal;
 HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IMP=investigational medicinal product; ITP=immune thrombocytopenia; IXRS= interactive voice/web response 
system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.  
b Visits 10, 12, and 14 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the final dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date.
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h The first 6 subjects will be enrolled in the Dose Arm 1 group only. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the 
DMC. Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, the subsequent subjects will be 
randomly assigned in 1:1 ratio to either Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in Dose Arm 1 and safety data review of at 
least 6 subjects in Dose Arm 2 is done, the subsequently enrolled subjects will be enrolled in Dose Arm 2 until a planned number of 15 subjects are enrolled.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 278 of 353
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m The IGRA test will be performed in a central laboratory. Any IGRA-positive subjects will be withdrawn from the study.
o Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see 
Section 12.4).
n Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
p In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 7 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
q
r This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
s A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only. 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 279 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
X
Platelets for inclusion/withdrawal 
check (local laboratory)g
X
X
X
Randomizationh
X
Withdrawal criteriai
X
X
X
X
General medical/procedures history
X
ITP history
X
Prior and concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 280 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Physical examinationj
X
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters (hematology, 
chemistry, urinalysis)
Xl
X
X
X
X
X
X
X
X
X
X
X
X
Serology test for HIV, hepatitis B, and 
hepatitis C
X
IGRA TB testm
X
TB signs and symptoms questionnaire
X
X
Blood sample for cytokines
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Whole blood sample for DNA 
(optional)
X
X
Whole blood sample for RNA 
(optional)
X
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
X
X
Call to IXRS for treatment kit number
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 281 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Administration of IMP
X
X
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
X
X
X
Serum complements (C3 and C4) and 
plasma complements (C3a and C5a)
X
X
X
X
Blood collection for exploratory safety 
biomarkers
X
Xo
X
X
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Serum BAFF levels
X
X
X
X
X
Blood collection for exploratory 
biomarker analysis
X
X
X
X
X
Immunoglobulins (total IgG, IgG 
subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEp
X
X
X
X
ITP-specific autoantibodiesq
X
X
X
ITP bleeding scale
X
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 282 of 353
Table 5‒2:
Schedule of assessments for the UCB7665 7mg/kg weekly dose arm (Dose Arm 2) 
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 
2
Dose 
3
Visit
1
2a
3
4a
5a
6
7
8b
9
10b
11
12b
13
BL Visit
EOS/
EWc
Day
-28 to -1
1
4
8
15
18
22
29
36
43
50
57
71
Week
1
1
2
3
3
4
5
6
7
8
9
11
Visit Window
±1d
±2dd
±2dd
±1d
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Headache questionnairer
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviews
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
 HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IGRA= interferon-gamma release assay; IMP=investigational medicinal product; ITP=immune thrombocytopenia; 
IXRS= interactive voice/web response system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; NFI-MS=Neurological Fatigue 
Index for multiple sclerosis; TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.
b Visits 8, 10, and 12 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the last dose.
d A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose. 
e The visit windows in the Observation Period are relative to the final dosing visit date. 
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h The first 6 subjects will be enrolled in the Dose Arm 1 group. Safety data for these 6 subjects up to 7 days after the last dose will be reviewed by the DMC. 
Following this review the DMC will make a decision to open Dose Arm 2 for enrollment. If Dose Arm 2 is opened, the subsequent subjects will be randomly 
assigned in 1:1 ratio to either Dose Arm 1 or Dose Arm 2 using an IXRS. Once 15 subjects are enrolled in Dose Arm 1 and safety data review of at least 
6 subjects in Dose Arm 2 is done, the subsequently enrolled subjects will be enrolled in Dose Arm 2 until a planned number of 15 subjects are enrolled.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 283 of 353
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m The IGRA test will be performed in a central laboratory. Any IGRA-positive subjects will be withdrawn from the study.
n Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
o Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see 
Section 12.4).
p In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 5 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
q
r This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
s A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
Change #35
Section 5.2
Schedule of study assessments
NEW tables added:
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Visit 
1
2a
3
4a
5
6
7b
8
9b
10
11b
12
BL 
Visit
EOS/EW
c
Telephone 
Contact
1
2d
3
4d
Day
-28 to -1
1
2
3
4
8
9
10
11
15
22
29
36
43
50
64
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 284 of 353
Week
1
1
1
1
2
2
2
2
3
4
5
6
7
8
10
Visit 
Window
±1d
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±1d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d f
Written informed consentg
X
Demographic data
X
Verification of 
inclusion/exclusion criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory) h
X
X
Withdrawal criteriai
X
X
X
General medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationj
X
X
X
X
X
X
X
12-lead ECGk
X
X
X
X
X
Karnofsky Performance 
Status
X
Laboratory parameters 
(hematology, chemistry, 
Xl
X
X
X
X
X
X
X
X
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 285 of 353
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Visit 
1
2a
3
4a
5
6
7b
8
9b
10
11b
12
BL 
Visit
EOS/EW
c
Telephone 
Contact
1
2d
3
4d
Day
-28 to -1
1
2
3
4
8
9
10
11
15
22
29
36
43
50
64
Week
1
1
1
1
2
2
2
2
3
4
5
6
7
8
10
Visit 
Window
±1d
±2de
±1d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d f
urinalysis)
Serology test for HIV, 
hepatitis B, and hepatitis C
X
IGRA TB testm
X
TB signs and symptoms 
questionnaire
X
X
Blood sample for cytokines
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Whole blood sample for 
DNA (optional)
X
X
Whole blood sample for 
RNA (optional)
X
X
X
X
Serum pregnancy test
X
  
Urine pregnancy test
X
X
X
Call to IXRS for treatment 
kit number
X
X
Administration of IMP
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 286 of 353
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Visit 
1
2a
3
4a
5
6
7b
8
9b
10
11b
12
BL 
Visit
EOS/EW
c
Telephone 
Contact
1
2d
3
4d
Day
-28 to -1
1
2
3
4
8
9
10
11
15
22
29
36
43
50
64
Week
1
1
1
1
2
2
2
2
3
4
5
6
7
8
10
Visit 
Window
±1d
±2de
±1d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d f
Blood sampling for plasma 
concentration of UCB7665
X
X
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
X
X
Serum complements (C3 
and C4) and plasma 
complements (C3a and C5a)
X
X
X
Blood collection for 
exploratory safety 
biomarkers
X
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Serum BAFF levels
X
X
X
X
Blood collection for 
exploratory biomarker 
analysis
X
X
X
X
Immunoglobulins (total 
IgG, IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgEp
X
X
X
X
ITP-specific autoantibodiesq
X
X
X
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D
X
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pport any marketing authorization application and any extensions or variations thereof.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 287 of 353
Table 5-3:
Schedule of assessments for the UCB7665 10mg/kg once weekly dose arm (Dose Arm 3)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Dose 2
Visit 
1
2a
3
4a
5
6
7b
8
9b
10
11b
12
BL 
Visit
EOS/EW
c
Telephone 
Contact
1
2d
3
4d
Day
-28 to -1
1
2
3
4
8
9
10
11
15
22
29
36
43
50
64
Week
1
1
1
1
2
2
2
2
3
4
5
6
7
8
10
Visit 
Window
±1d
±2de
±1d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d
f
±2d f
ITP bleeding scale
X
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairer
X
X
X
X
X
X
X
X
X
X
X
Subject exit interviews
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal;
HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IGRA= interferon-gamma release assay; IMP=investigational medicinal product; ITP=immune 
thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; 
NFI-MS=Neurological Fatigue Index for multiple sclerosis; TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.
b Visits 7, 9, and 11 can be performed at home with a healthcare professional visiting the subject at his/her home.
c The End-of-Study Visit is 8 weeks following the last dose.
d If the TC is on the same day as an on-site visit, the TC may be skipped.
e A visit window of ±2 days is allowed for the dosing visits. The visit window of ±2 days is relative to the first dosing visit date. However, there should be a 
minimum interval of 5 days and maximum interval of 9 days as compared to the previous dose.
f The visit windows in the Observation Period are relative to the final dosing visit date. 
g Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
REDACTED COPY 
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This document canno
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 288 of 353
h Prior to dosing at Visit 2, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
i Subjects can withdraw at any time during the study, based on the criteria in Section 6.4. 
j A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
k The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
l At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
m The IGRA test will be performed in a central laboratory. Any IGRA-positive subjects will be withdrawn from the study.
n Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
o Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see 
Section 12.4).
p In case the number of infusions to be administered are reduced after DMC review of safety data, then the scheduled Visit 6 assessment for IgA, IgM, and IgE 
will be performed earlier at the last dosing visit.
q
r This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
s A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 289 of 353
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose Arm 4)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of 
inclusion/exclusion criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)g
X
Withdrawal criteriah
X
General medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
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port any marketing authorization application and any extensions or variations thereof.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 290 of 353
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose Arm 4)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
12-lead ECGj
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xk
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis C
X
IGRA TB testl
X
TB signs and symptoms 
questionnaire
X
X
Blood sample for cytokines
X
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Whole blood sample for DNA 
(optional)
X
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pport any marketing authorization application and any extensions or variations thereof.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 291 of 353
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose Arm 4)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Whole blood sample for RNA 
(optional)
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
Call to IXRS for treatment kit 
number
X
Administration of IMP
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
Serum complements (C3 and 
C4) and plasma complements 
(C3a and C5a)
X
X
X
Blood collection for 
exploratory safety biomarkers
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Serum BAFF levels
X
X
X
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OP
ED
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d
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 292 of 353
Table 5-4:
Schedule of assessments for the UCB7665 15mg/kg once dose arm (Dose Arm 4)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Blood collection for 
exploratory biomarker 
analysis
X
X
X
Immunoglobulins (total IgG, 
IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgE
X
X
X
ITP-specific autoantibodieso
X
X
X
ITP bleeding scale
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairep
X
X
X
X
X
X
X
X
X
Subject exit interviewq
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal;
HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IGRA= interferon-gamma release assay; IMP=investigational medicinal product; ITP=immune 
thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; 
NFI-MS=Neurological Fatigue Index for multiple sclerosis; TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.
b Visits 5, 7, and 9 can be performed at home with a healthcare professional visiting the subject at his/her home.
REDACTED COPY 
PY
TE
OP
CTE
TE
TE
E
T
RE
RE
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rt any marketing authorization application and any extensions or variations thereof.
d
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This document ca
perform
can
perform


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 293 of 353
c The End-of-Study Visit is 8 weeks following the dose.
d If the TC is on the same day as an on-site visit, the TC may be skipped.
e The visit windows in the Observation Period are relative to the dosing visit date. 
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 1, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
i A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
j The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
k At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
l IGRA test will be performed in a central laboratory. It is recommended that the QFT-GIT be the first test performed at Screening to reduce the number of 
screening procedures conducted for any IGRA-positive subjects that may need to be withdrawn from the study.
m Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
n Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see 
Section 12.4).
o
p This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
q A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 294 of 353
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose Arm 5)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Written informed consentf
X
Demographic data
X
Verification of 
inclusion/exclusion criteria
X
X
Platelets for inclusion/ 
withdrawal check (local 
laboratory)g
X
Withdrawal criteriah
X
General medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medical 
procedures
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 295 of 353
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose Arm 5)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationi
X
X
X
X
X
X
12-lead ECGj
X
X
X
X
Karnofsky Performance Status
X
Laboratory parameters 
(hematology, chemistry, 
urinalysis)
Xk
X
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis C
X
IGRA TB testl
X
TB signs and symptoms 
questionnaire
X
X
Blood sample for cytokines
X
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Whole blood sample for DNA 
(optional)
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 296 of 353
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose Arm 5)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Whole blood sample for RNA 
(optional)
X
X
X
Serum pregnancy test
X
Urine pregnancy test
X
X
Call to IXRS for treatment kit 
number
X
Administration of IMP
X
Blood sampling for plasma 
concentration of UCB7665
X
X
X
Anti-UCB7665 antibodies
X
X
X
X
X
X
X
Serum complements (C3 and 
C4) and plasma complements 
(C3a and C5a)
X
X
X
Blood collection for 
exploratory safety biomarkers
X
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Serum BAFF levels
X
X
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 297 of 353
Table 5-5:
Schedule of assessments for the UCB7665 20mg/kg once dose arm (Dose Arm 5)
Assessments
Screening 
Period
Dosing Period
Observation Period
Dose 1
Visit 
1
2a
3
4
5b
6
7b
8
9b
10
BL Visit
EOS/EWc
Telephone 
Contact
1
2d
Day
-28 to -1
1
2
3
4
8
15
22
29
36
43
57
Week
1
1
1
1
2
3
4
5
6
7
9
Visit 
Window
±1de
±2de
±2de
±2de
±2de
±2de
±2de
±2de
Blood collection for 
exploratory biomarker 
analysis
X
X
X
Immunoglobulins (total IgG, 
IgG subclasses) 
X
X
X
X
X
X
X
X
X
X
IgA, IgM, IgE
X
X
X
ITP-specific autoantibodieso
X
X
X
ITP bleeding scale
X
X
X
X
X
X
NFI-MS
X
X
X
X
X
Headache questionnairep
X
X
X
X
X
X
X
X
X
Subject exit interviewq
X
AE=adverse event; BAFF=B cell activating factor; BL=Baseline; CSF=cerebrospinal fluid; CT=computed tomography; d=day(s); DMC=Data Monitoring 
Committee; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EW=Early Withdrawal; 
HIV=human 
immunodeficiency virus; Ig=immunoglobulin; IGRA= interferon-gamma release assay; IMP=investigational medicinal product; ITP=immune 
thrombocytopenia; IXRS= interactive voice/web response system; LP=lumbar puncture; RNA=ribonucleic acid; MRI=magnetic resonance imaging; 
NFI-MS=Neurological Fatigue Index for multiple sclerosis; TB=tuberculosis.
a Frequency of assessments on dosing days is detailed in Table 5‒6.
b Visits 5, 7, and 9 can be performed at home with a healthcare professional visiting the subject at his/her home.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 298 of 353
c The End-of-Study Visit is 8 weeks following the dose.
d If the TC is on the same day as an on-site visit, the TC may be skipped.
e The visit windows in the Observation Period are relative to the dosing visit date. 
f Additional informed consent is needed for participation in the exploratory genomic substudy. All samples will be collected prior to dosing with IMP.
g Prior to dosing at Visit 1, 2 platelet samples will be taken. One sample will be analyzed locally and the value will be used to check inclusion criteria. The other 
platelet sample will be sent to the central laboratory. At subsequent dosing visits, a platelet sample will be assessed locally prior to dosing to evaluate 
withdrawal criterion of platelet count >350x109/L.
h Subjects can withdraw at any time during the study, based on the criteria in Section 6.4.
i A complete physical examination will be performed at Screening and EOS/EW Visit. At all other visits (where physical examination is performed), an 
abbreviated physical examination will be conducted.
j The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
k At the Screening Visit, 2 separate blood samples will be obtained on the same day for evaluation of platelet count.
l The IGRA test will be performed in a central laboratory. Any IGRA-positive subjects will be withdrawn from the study.
m Blood sample for cytokines will be obtained and analyzed at baseline for all subjects and at subsequent visits only in subjects with infusion reactions.
n Exploratory safety biomarker samples to be obtained on dosing days for all subjects. During non-dosing visits and during the visits in the Observation Period, 
the samples should be obtained only from subjects experiencing severe headaches or GI disturbances (only in case of Adverse Events of Interest, see 
Section 12.4). 
o
p This assessment is applicable only to subjects experiencing severe headaches and will be performed daily until resolution (ie, if headache becomes moderate or 
mild, normal collection of AEs should apply); this assessment will be followed by a neurological assessment (including fundoscopy). Additionally, other 
diagnostic procedures including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if indicated at the discretion of the investigator, 
considering the local guidelines for performing LP in subjects with ITP.
q A semi-structured interview guide will be used and the interview will be recorded. In case of early withdrawal from the study, the subject exit interview should 
be performed at End-of-Study Visit only.
Change #36
Section 5.2
Schedule of study assessments
Table 5‒3:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of infusion
4h after end of infusion
Withdrawal criteria
X
Platelet count (local laboratory) for inclusion check 
at Visit 2 and for withdrawal criterion at other 
dosing visits
X
Prior and concomitant medications
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 299 of 353
Table 5‒3:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of infusion
4h after end of infusion
Concomitant medical procedures
X
Vital signsa
X
X
X
X
Physical examination
X
12-lead ECG
X
Hematology 
X
Clinical chemistry
X
Urinalysis
X
Urine pregnancy test
X
Immunoglobulinsb
X
ITP-specific autoantibodiesc
X
Blood sampling for UCB7665 plasma 
concentration
X
Anti-UCB7665 antibodies/IgG depletion assay
X
Serum (C3 and C4) and plasma complements (C3a
and C5a)d
X
Serum biomarkers 
X
X
X
Serum BAFF levels
X
X
X
Blood sampling for cytokinese
X
ITP bleeding scale
X
AEs
X
X
X
X
NFI-MSf
X
AE=adverse event; BAFF=B cell activating factor; ECG=electrocardiogram; h=hours; Ig=immunoglobulin; IMP=investigational medicinal product; 
ITP=immune thrombocytopenia; NFI-MS=Neurological Fatigue Index for multiple sclerosis; 
 PRO=Patient Reported 
Outcomes; 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 300 of 353
a In addition to time points mentioned, vital signs will be evaluated every 15 minutes during infusion. Respiratory rate will be assessed only once predose.
b Total IgG and IgG subclasses. 
c Evaluation of ITP-specific autoantibodies will be performed prior to dose 1 only. 
d Serum and plasma complement levels will be assessed prior to dose 1 and dose 3 only.
e Blood sample for Baseline cytokine values will be obtained at Visit 2 for all subjects at predose and at other visits in case of infusion reactions.
f PRO endpoint (NFI-MS) will be assessed prior to dose 1 only.
Has been changed to:
Table 5‒6:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of 
infusion
4h after end of 
infusion
6h after end of 
infusiona
Withdrawal criteria
X
Platelet count (local laboratory) for 
inclusion check at Visit 2 and for 
withdrawal criterion at other dosing visits
X
Prior and concomitant medications
X
Concomitant medical procedures
X
Vital signsb
X
X
X
X
X
Physical examination
X
12-lead ECGc
X
Hematology 
X
Clinical chemistry
X
Urinalysis
X
Urine pregnancy test
X
Immunoglobulinsd
X
ITP-specific autoantibodiese
X
Blood sampling for UCB7665 plasma 
concentration
X
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 301 of 353
Table 5‒6:
Schedule of investigations on the dosing days
Predose
End of infusion
2h after end of 
infusion
4h after end of 
infusion
6h after end of 
infusiona
Anti-UCB7665 antibodies
X
Serum (C3 and C4) and plasma 
complements (C3a and C5a)f
X
Blood collection for exploratory safety 
biomarkersg
X
X
X
Serum BAFF levels
X
Blood collection for exploratory 
biomarker analysis
X
Blood sampling for cytokines
Xh
Xi
Whole blood sample for DNA and RNA 
(optional)j
X
ITP bleeding scale
X
AEs
X
X
X
X
X
NFI-MSk
X
AE=adverse event; BAFF=B cell activating factor; DNA=deoxyribonucleic acid; ECG=electrocardiogram; h=hours; Ig=immunoglobulin; IMP=investigational 
medicinal product; ITP=immune thrombocytopenia; NFI-MS=Neurological Fatigue Index for multiple sclerosis; PRO=Patient Reported Outcomes; 
RNA=ribonucleic acid; 
a For Dose Arms 3, 4 and 5 only
b In addition to time points mentioned, vital signs will be evaluated every 15 minutes during infusion. Respiratory rate will be assessed only once predose.
c The ECG should be performed in triplicate prior to blood collection for assessment of laboratory parameters. Three ECGs should be recorded in a time frame of 
5 minutes with at least 1 minute difference, 1-2 minutes between the ECGs.
d Total IgG and IgG subclasses. 
e Evaluation of ITP-specific autoantibodies will be performed prior to dose 1 only. 
f Serum and plasma complements (C3a and C5a) will be assessed prior to dose 1 and dose 3 only.
g
h Blood sample for Baseline cytokine values will be obtained and analyzed at Baseline (Visit 2) pre-dose for all subjects. Also for all subjects on Dose Arm 3, the 
blood sample for cytokine values will be obtained and analyzed at Visit 4 pre-dose.
i Additional cytokine blood sample to be taken at 4h after end of infusion only in subjects with infusion reaction.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 302 of 353
j For DNA, samples are taken at Baseline (Visit 2) and last dose only. For RNA, samples are taken at Baseline (Visit 2), Visit 3, at last dose, and End of Study 
Visit. All samples collected prior to dosing (if applicable for visit).
k PRO endpoint (NFI-MS) will be assessed prior to dose 1 only.
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 303 of 353
Change #37
Section 5.3
Schematic diagram
Figure 5‒1: Schematic diagram
RED
EDACTED COPY 
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authorization application and any extensions or variat


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15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 304 of 353
Has been changed to:
Change #38
Section 5.4.3 Choice of study design endpoints
Paragraph #1:
The primary objective of the study is evaluation of safety and tolerability of UCB7665 
administered as an sc infusion in subjects with ITP. The study utilizes a sequential adaptive 
design with at least 4 interim analyses as described in Section 14.7. This design was chosen to 
permit adequate monitoring of the safety of the subjects in the study.
Has been changed to:
The primary objective of the study is evaluation of safety and tolerability of UCB7665 
administered as an sc infusion in subjects with ITP. The study utilizes a sequential adaptive 
design with at least 11 interim analyses as described in Section 14.7. This design was chosen to 
permit adequate monitoring of the safety of the subjects in the study.
Change #39
5.4.5
Rationale for dose seletion
Paragraph #5:
Therefore, doses of UCB7665 4mg/kg given once weekly for 5 weeks and UCB7665 7mg/kg 
given once weekly for 3 weeks have been selected to evaluate the safety, tolerability and effect 
on platelet count in subjects with primary persistent or chronic ITP.
REDAC
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5.4.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 305 of 353
Has been changed to:
Therefore, doses of UCB7665 4mg/kg given once weekly for 5 weeks(Dose Arm 1) and 
UCB7665 7mg/kg given once weekly for 3 weeks (Dose Arm 2) have been selected as the initial 
doses to evaluate the safety, tolerability and effect on platelet count in subjects with primary 
persistent or chronic ITP. Both dose regimens have the same cumulative dose of approximately 
UCB7665 20mg/kg.
New paragraph #6 added:
Preliminary data from the current study indicates that the current dose regimens of UCB7665 
4mg/kg and UCB7665 7mg/kg have been well tolerated. Hence the additional dose regimens of 
UCB7665 10mg/kg given once weekly for 2 weeks (Dose Arm 3) and of UCB7665 20mg/kg 
given once only (Dose Arm 5) are planned to further investigate the safety, tolerability and effect 
on platelet count of the same cumulative dose of UCB7665 20mg/kg but administered in dose 
regimes with higher dosages given in less infusions. The dose of UCB7665 15mg/kg given once 
only (Dose Arm 4) has been selected in addition as a risk mitigation as it is bridging the dose of 
UCB7665 10mg/kg given once weekly for 2 weeks (Dose Arm 3) and the dose of UCB7665 
20mg/kg given once only (Dose Arm 5).
Change #40
NEW Section 5.4.6
Justification for additional genomic analyses
DNA analysis
A genetic component in ITP has long been suspected to predispose some persons to develop ITP 
when exposed to a provocative event.
Further, the hypothesis of underlying genetic risk for ITP is supported by rare anecdotal and case 
reports of familial ITP. Affected members of these families present with ITP that meets the 
clinical criteria for primary ITP, but demonstrates a convincing pattern of inheritance. A 2006 
review of the Pediatric and Adult Registry of Chronic ITP (PARC-ITP) (Johnsen, 2012) found 
that 10 of 445 (2.2%) of pediatric patients reported a positive family history of ITP. However, 
identification of susceptibility genes in ITP, via family linkage studies or genome wide 
association studies, have not yet been forthcoming, likely due to the rarity of familial ITP 
families available for study and the heterogeneity of ITP sporadic cases. Identification and 
characterization of a genetic and/or epigenetic component of familial ITP will lead to important 
clues into the pathogenesis of more common forms of ITP and possibly advance understanding 
of drug response phenotypes. 
RNA analysis
Gene expression (mRNA) analyses have identified distinct gene transcription signatures from 
whole blood associated with many autoimmune diseases including rheumatoid arthritis, systemic 
lupus erythematosus, and ITP. Such signatures have provided molecular insight into disease 
biology and can facilitate patient stratification via gene expression panels predictive of 
therapeutic response and clinical outcomes. 
Collection of blood for RNA analysis will enable identification of candidate markers for 
treatment effect and safety, and determine the feasibility of patient stratification.
MicroRNA analysis
REDACTED COPY
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RED
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof.
665 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 306 of 353
MicroRNA are short (19-25 nucleotides) evolutionarily conserved single-stranded RNA 
molecules that regulate the expression of genes involved in diverse biological processes. The 
effect of miRNA on mRNA is mediated through the binding of the miRNA to the target mRNA 
ribonucleoprotein complex resulting in altered expression and decreased protein translation.  
Regulated miRNA in ITP significantly affect both gene and protein expression in T cells, 
indicating that they may be important regulatory molecules involved in the loss of immune 
tolerance in ITP.
In summary, the genetic, epigenetic, and genomic elements of ITP are complex and require 
further elucidation to understand the cause, progression, and appropriate treatment of ITP. 
Through the voluntary collection of blood DNA/and RNA samples from consenting subjects, this 
substudy will help enable further investigation of this complex disease.
Change #41
Section 6.1
Inclusion criteria
7. Female subjects of childbearing potential must have a negative serum pregnancy test at the 
Screening Visit, which is confirmed to be negative by urine testing prior to the first dose of 
IMP at Week 1 (Visit 2) and prior to further dosing at each study visit thereafter. 
Female subjects of childbearing potential must agree to use a highly effective method of 
birth control, during the study and for a period of 3 months after their final dose of IMP. 
Highly effective forms of birth control are methods which achieve a failure rate of less than 
1% per year when used consistently and correctly. Highly effective methods of birth control 
include:
…
Has been changed to:
7. Female subjects of childbearing potential must have a negative serum pregnancy test at the 
Screening Visit, which is confirmed to be negative by urine testing prior to the first dose of 
IMP at Week 1 (Visit 2) and prior to further dosing at each study visit thereafter. 
Female subjects of childbearing potential must agree to use a highly effective method of 
birth control, during the study and for a period of 2 months after their final dose of IMP. 
Highly effective forms of birth control are methods which achieve a failure rate of less than 
1% per year when used consistently and correctly. Highly effective methods of birth control 
include:
…
Change #42
Section 6.2.1 Exclusion criteria related to health status
9. Subject has renal impairment, defined as:
Serum creatinine level of ≥1.4 mg/dL for females and ≥1.5 mg/dL for males at 
Screening Visit.
10. Subject has liver impairment, defined as:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 307 of 353
Subject has >1.5xULN of any of the following: alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), or alkaline phosphatase (ALP), or >ULN total bilirubin (≥1.5xULN 
total bilirubin if known Gilbert’s syndrome). If the subject has elevations only in total 
bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible 
undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%).
…
Has been changed to:
9. Subject has renal impairment, defined as:
Serum creatinine level of ≥1.4mg/dL for females and ≥1.5mg/dL for males at Screening 
Visit. 
10. Subject has 2xULN of any of the following: alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), or alkaline phosphatase (ALP), or >ULN total bilirubin (≥1.5xULN 
total bilirubin if known Gilbert’s syndrome). If the subject has elevations only in total bilirubin 
that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert’s 
syndrome (ie, direct bilirubin <35%).
…
Change #43
6.2.2
Exclusion criteria related to medical history
NEW exclusion criteria added:
25. Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or 
with latent TB (LTB) infection or current history of nontuberculous mycobacterial infection 
(NTMBI) infection are excluded.
a. Known TB infection whether present or past is defined as:

Active TB infection or clinical signs and symptoms suggestive of TB (pulmonary or 
extrapulmonary).

History of active TB infection involving any organ system or findings in other organ systems 
consistent with TB infection.

Any historical evidence by radiography or other imaging modalities consistent with 
previously active TB infection.

b. High risk of acquiring TB infection is defined as:

Known exposure to another person with active TB infection within the 3 months prior to 
Screening.

Time spent in a healthcare delivery setting or institution where individuals infected with TB 
are housed and where the risk of transmission of infection is high.
c. LTB infection (refer to Section 12.8.1 for further details and instructions).
d. NTMBI is defined as a group of lung infections caused by mycobacteria different from 
mycobacterium tuberculosis infections.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 308 of 353
26 Subjects with known TB infection, at high risk of acquiring TB infection, or LTB infection, 
or current/history of NTMBI are excluded.
Change #44
6.4 Withdrawal criteria
2. Subject develops an illness or has a change in health status that would interfere with 
his/her continued participation, including but not limited to:

Subject has a serious infective episode requiring hospitalization or iv antibiotic therapy 
(including but not limited to bacteremia or sepsis, bacterial meningitis, osteomyelitis or 
septic arthritis, bacterial pneumonia, or visceral abscess). 

Subject experiences a severe AE of gastrointestinal disturbance or headache which is 
considered related to the IMP in the opinion of the investigator.

Subject has a severe infusion reaction requiring corticosteroid and/or epinephrine 
therapy.

Subject has an anaphylactic reaction requiring corticosteroid and/or epinephrine therapy.

Subject has a life threatening bleeding event.
Has been changed to:
2. Subject develops an illness or has a change in health status that would interfere with his/her 
continued participation, including but not limited to:

Subject has a serious infective episode requiring hospitalization or iv antibiotic therapy 
(including but not limited to bacteremia or sepsis, bacterial meningitis, osteomyelitis or 
septic arthritis, bacterial pneumonia, or visceral abscess). 

Subject experiences a severe AE of gastrointestinal disturbance or headache which is 
considered related to the IMP in the opinion of the investigator.

Subject has a severe infusion reaction requiring corticosteroid and/or epinephrine 
therapy.

Subject has an anaphylactic reaction requiring corticosteroid and/or epinephrine therapy.

Subject has a life threatening bleeding event.

Subject has a TB test that is confirmed positive or any further evidence suggestive of
potential TB infection (eg, close exposure) and further examinations result in a diagnosis 
of active TB or LTB. Refer to Section 12.8.1 for further details and instructions.

If an NTMBI infection is identified during a study, the same withdrawal procedures as 
those used for an active TB infection identified during the study should be followed.
Change #45
6.4 Withdrawal criteria
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 309 of 353
Subjects MUST stop treatment with the IMP if the platelet count is >350x109/L during the 
Dosing Period. Subjects should continue in the study and attend the protocol defined visits in the 
Observation Period.
Subjects with PDILI must be assessed to determine if IMP must be discontinued. In addition, all 
concomitant medications and herbal supplements that are not medically necessary should also be 
discontinued.
Has been changed to:
Subjects MUST stop treatment with the IMP if the platelet count is >350x109/L during the 
Dosing Period. Subjects should continue in the study and attend the protocol defined visits in the 
Observation Period.
6.4.1 Potential drug induced liver injury IMP discontinuation criteria
Subjects with PDILI must be assessed to determine if IMP must be discontinued. In addition, all 
concomitant medications and herbal supplements that are not medically necessary should also be 
discontinued.
Change #46
6.5 Study stopping rules 
More detailed criteria for stopping a cohort will be defined in the DMC charter.
Has been changed to:
More detailed criteria for stopping a dose arm will be defined in the DMC charter.
Change #47
Section 7.2 Treatment to be administered 
Subjects in Dose Arm 1 will receive 5 sc doses of UCB7665 4mg/kg at 1-week intervals. 
Subjects in Dose Arm 2 will receive 3 sc doses of UCB7665 7mg/kg at 1-week intervals.
Has been changed to:
Subjects in Dose Arm 1 will receive 5 sc doses of UCB7665 4mg/kg at 1-week intervals. 
Subjects in Dose Arm 2 will receive 3 sc doses of UCB7665 7mg/kg at 1-week intervals. 
Subjects in Dose Arm 3 will receive 2 sc doses of UCB7665 10mg/kg at a 1-week interval.
Subjects in Dose Arm 4 will receive 1 sc dose of UCB7665 15mg/kg.
Subjects in Dose Arm 5 will receive 1 sc dose of UCB7665 20mg/kg.
Change #48
Section 7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Conference on 
Harmonisation (ICH) guidelines on GCP and GMP and will include any locally required 
statements. If necessary, labels will be translated into the local language.
Has been changed to:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 310 of 353
Clinical drug supplies will be labeled in accordance with the current International Council for 
Harmonisation (ICH) guidelines on GCP and GMP and will include any locally required 
statements. If necessary, labels will be translated into the local language.
Change #49
7.8.3
Rescue medication
In the case of prolonged hypogammaglobulinemia the subject will be considered for treatment 
with prophylactic antimicrobial therapy. Subjects will be followed up until immunoglobulin 
levels return to within the normal range.
In case of lack of efficacy and/or severe bleeding events and where appropriate, platelet 
substitution or treatment with a commercially available iv immunoglobulin may be considered.
Has been changed to:
In the case of prolonged hypogammaglobulinemia the subject will be considered for treatment 
with prophylactic antimicrobial therapy. Subjects will be followed up until immunoglobulin 
levels return to within the normal range.
In case of lack of efficacy and/or severe bleeding events and where appropriate, platelet 
substitution or treatment with a commercially available iv immunoglobulin may be considered.
If such rescue medication must be given when the subject is still in the dosing period, the subject 
should be withdrawn from the study treatment and complete all Observation visits, if possible. 
If such rescue medication is given when the subject has completed the study treatment, the 
subject should continue the Observation Visits, as per schedule of study assessments 
(Section 5.2).
Change #50
Section 7.10
Randomization and numbering of subjects
Paragraph #2:
The first 6 subjects (and those treated before DMC assessment after the 6 subjects) will not be 
randomized. Once the DMC has approved opening of Dose Arm 2 for enrollment, subsequent 
subjects will be randomized to 1 of the 2 dose arms in a 1:1 ratio. Once 15 subjects are in the 
4mg/kg group, the remaining subjects will not be randomized. They will be allocated to the 
7mg/kg group.
Has been changed to:
An IXRS will be used for assigning eligible subjects to a treatment regimen based on a 
predetermined production randomization and/or packaging schedule provided by PAREXEL 
Informatics. The IXRS will generate individual assignments for subject kits of IMP, as 
appropriate, according to the dose arm and subject’s weight.
The first 6 subjects (and those treated before DMC assessment after the 6 subjects) will not be 
randomized. Once the DMC has advocated the initiation of Dose Arm 2 for enrollment, 
subsequent subjects will be randomly assigned to 1 of the 2 dose arms (ie, Dose Arm 1 and Dose 
Arm 2) in a 1:1 ratio. Once 15 subjects are enrolled in the Dose Arm 1, the remaining subjects 
will be enrolled in Dose Arm 2 until Dose Arm 2 is completed with 15 subjects.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 311 of 353
After Dose Arm 2, there will be no randomization between dose arms.
Change #51
Section 8.1.1 Visit 1 (Day -28 to -1) Screening Visit
Has been changed to:
Section 8.1.1 Visit 1 (Day -28 to -1) Screening Visit (all Dose Arms)
Detail regarding informed consent process for exploratory genomic analyses added as follows:
Subjects will also have the option of providing additional voluntary informed consent for 
collection of whole blood samples for exploratory DNA and RNA analyses.
Change #52
Section 8.1.1
Visit (Day -28 to -1) Screening Visit 
…

12-lead ECG

Karnofsky Performance Status

Recording of AEs

Urine sample for urinalysis

Blood sample for the following laboratory parameters:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry* 

Serum pregnancy test for women of childbearing potential

Serum total IgG and IgG subclasses concentration 

Serum HbA1c 

Serology tests for HIV, hepatitis B, and hepatitis C

ITP bleeding scale
*Two blood samples for assessment of platelet count to be obtained via 2 separate blood 
collections
Has been changed to:
…

12-lead ECG (triplicate)

Karnofsky Performance Status

Recording of AEs

Urine sample for urinalysis

Blood sample for the following:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 312 of 353

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry (two blood samples for assessment of platelet count to be obtained via 2 
separate blood collections)

Serum pregnancy test for women of childbearing potential

Serum total IgG and IgG subclasses concentration 

Serum HbA1c 

Serology tests for HIV, hepatitis B, and hepatitis C

ITP bleeding scale
NEW bullet points added:
…

Obtain informed consent for substudy involving DNA and RNA analyses
…

IGRA TB test

TB signs and symptoms questionnaire
Change #53
Section 8.2 Dosing Period
Has been changed to:
Section 8.2 Dosing Period for all Dose Arms 
Change #54
Section 8.2.1 Visit 2 (Week 1/Day 1) Baseline Visit
Paragraphs #2, #3, and #4:
Eligible subjects will be treated with IMP at Visit 2. The first 6 subjects will be enrolled in Dose 
Arm 1, subsequent subjects will be randomized to 1 of the 2 dose arms. Once 15 subjects are in 
Dose Arm 1, the remaining subjects will not be randomized. They will be allocated to Dose 
Arm 2. 
Eligible subjects will be treated with IMP at Visit 2. The first 6 subjects will be enrolled in Dose 
Arm 1, subsequent subjects will be randomized to 1 of the 2 dose arms. Once 15 subjects are in 
Dose Arm 1, the remaining subjects will not be randomized. They will be allocated to Dose 
Arm 2. 
Subjects allocated to Dose Arm 1 (UCB7665 4mg/kg sc) will receive a total of 5 doses of IMP at 
Visit 2 (Day 1, Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), and Visit 7 
(Week 5). 
Subjects allocated to Dose Arm 2 (UCB7665 7mg/kg sc) will receive a total of 3 doses of IMP at 
Visit 2 (Day 1, Week 1), Visit 4 (Week 2), and Visit 5 (Week 3).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 313 of 353
Has been changed to:
Eligible subjects will be treated with IMP at Visit 2. 
Subjects allocated to Dose Arm 1 (UCB7665 4mg/kg weekly sc) will receive a total of 5 doses of 
IMP at Visit 2 (Day 1, Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), and 
Visit 7 (Week 5). 
Subjects allocated to Dose Arm 2 (UCB7665 7mg/kg weekly sc) will receive a total of 3 doses of 
IMP at Visit 2 (Day 1, Week 1), Visit 4 (Week 2), and Visit 5 (Week 3). 
Subjects allocated to Dose Arm 3 (UCB7665 10mg/kg weekly sc) will receive a total of 2 doses 
of IMP at Visit 2 (Day 1, Week 1) and Visit 4 (Day 8, Week 2). 
Subjects allocated to Dose Arm 4 (UCB7665 15mg/kg) will receive 1 dose of IMP at Visit 2 
(Day 1, Week 1).
Subjects allocated to Dose Arm 5 (UCB7665 20mg/kg) will receive 1 dose of IMP at Visit 2 
(Day 1, Week 1).
Change #55
8.2.1
Visit 2 (Week 1/Day 1) Baseline Visit 

12-lead ECG

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Blood sample for the following laboratory parameters:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies/IgG depletion assay

Serum total IgG and IgG subclasses concentration 

Serum IgA, IgM, and IgE concentration

ITP-specific autoantibodies 

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the inclusion 
criteria of platelet count <35x109/L at Baseline

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Serum biomarkers 
 and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF

Serum cytokines
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 314 of 353
NEW bullet points:

Subjects in Dose Arms 1 and 2 will stay on site for 4 hours after the end of infusion for 
inpatient observation at the site.

Subjects in Dose Arms 3, 4 and 5 will stay on site for 6 hours after the end of infusion for 
inpatient observation at the site.
Has been changed to:

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Blood sample for the following:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration 

Serum IgA, IgM, and IgE concentration

ITP-specific autoantibodies 

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the inclusion 
criteria of platelet count <35x109/L at Baseline

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Exploratory safety biomarkers
. Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety 
biomarkers

Serum BAFF levels

Exploratory biomarker analysis

Serum cytokines mandatory for all subjects at pre-dose, and only in case of infusion 
reactions at 4 hours after end of infusion

Collection of whole blood for exploratory DNA and RNA analyses
Change #56
8.2.2
Visit 3 (Week 1/Day 4)
…

Blood sample for the following laboratory parameters:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 315 of 353

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665

Anti-UCB7665 antibodies/IgG depletion assay

Serum total IgG and IgG subclasses concentration

Serum biomarkers

Review withdrawal criteria

Serum cytokines, only in case of infusion reactions
…
Has been changed to:
8.2.2
Visit 3 (Week 1/Day 4) [UCB7665 4mg/kg, UCB7665 7mg/kg, and UCB7665 10mg/kg]
…

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

Exploratory safety biomarkers
 only from 
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4)

Review withdrawal criteria

Serum cytokines, only in case of late infusion reactions visible during the visit
For Dose Arm 1, 2, and 3 collection of whole blood for exploratory RNA analyses
…
Change #57
8.2.3
Visit 4 (Week 2/Day 8)
…

12-lead ECG

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 316 of 353

Blood sample for the following laboratory parameters:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies/IgG depletion assay

Serum total IgG and IgG subclasses concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Serum biomarkers
 and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF
…
Has been changed to:
8.2.3
Visit 4 (Week 2/Day 8) [UCB7665 4mg/kg, UCB7665 7mg/kg and UCB7665 10mg/kg]
…

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory serum 
biomarkers

Serum BAFF levels

Exploratory biomarker analysis
…
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 317 of 353
NEW bullet points:

Subjects in Dose Arms 1 and 2 will stay on site for 4 hours after the end of infusion for 
inpatient observation at the site.

Subjects in Dose Arms 3, 4 and 5 will stay on site for 6 hours after the end of infusion for 
inpatient observation at the site.

For Dose Arm 3, only collection of whole blood for exploratory DNA and RNA analyses
…

Serum cytokines at pre-dose mandatory for subjects on Dose Arm 3 (10mg/kg), and at 4 
hours after end of infusion (for all dose arms)
Change #58
8.2.4
Visit 5 (Week 3/Day 15)
…

12-lead ECG

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following laboratory parameters:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies/IgG depletion assay

Serum total IgG and IgG subclasses concentration 

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Serum IgA, IgM, and IgE concentration (UCB7665 7mg/kg only)

Serum biomarkers 
 and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF
Has been changed to:
8.2.4
Visit 5 (Week 3/Day 15) [UCB7665 4mg/kg and UCB7665 7mg/kg]
…

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 318 of 353

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration 

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Serum IgA, IgM, and IgE concentration (UCB7665 7mg/kg only)

Exploratory safety biomarker
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety 
biomarkers

Serum BAFF levels

Exploratory biomarker analysis

For Dose Arm 2 only, collection of whole blood for exploratory DNA and RNA analyses 
…
Change #59
Visit 6 (Week 4/Day 22) [UCB7665 4mg/kg only]

12-lead ECG

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following laboratory parameters:

Plasma concentration of UCB7665 

Anti-UCB7665 antibodies/IgG depletion assay

Serum total IgG and IgG subclasses concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 319 of 353

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Serum biomarkers 
 and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF
Has been changed to:
8.2.5
Visit 6 for Dose Arm 1 (Week 4/Day 22) [UCB7665 4mg/kg only]

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following:

Plasma concentration of UCB7665 

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety
biomarkers

Serum BAFF levels

Exploratory biomarker analysis
Change #60
8.2.6
Visit 7 (Week 5/Day 29) [UCB7665 4mg/kg only]

12-lead ECG

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following laboratory parameters:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies/IgG depletion assay
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 320 of 353

Serum total IgG and IgG subclasses concentration

Serum IgA, IgM, and IgE concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Serum biomarkers 
 and 
serum BAFF levels. Blood samples are taken prior to dosing, 2 and 4 hours after end of 
infusion for serum biomarkers and BAFF
Has been changed to:

12-lead ECG (triplicate)

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Call IXRS to obtain treatment kit number(s)

Blood sample for the following:

Plasma concentration of UCB7665

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

Serum IgA, IgM, and IgE concentration

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Additional platelet sample for analysis in local laboratory for evaluation of the 
withdrawal criteria of platelet count >350x109/L

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety
biomarkers

Serum BAFF levels

Exploratory biomarker analysis

For Dose Arm 1 only, collection of whole blood for DNA and RNA analyses
Change #61
NEW sections added:
8.3
Telephone Contacts 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 321 of 353
For Dose Arms 3, 4 and 5 the site must make a phone call to the subject on Day 1 and Day 2 
after dosing as a safety measure.
8.3.2
Telephone Contact 1 (Week 1/Day 2) [UCB7665 10mg/kg, UCB7665 15mg/kg, 
UCB7665 20mg/kg]

Concomitant medications

Concomitant medical procedures

Recording of AEs
8.3.3
Telephone Contact 2 (Week 1/Day 3) [UCB7665 10mg/kg, UCB7665 15mg/kg, 
UCB7665 20mg/kg]

Concomitant medications

Concomitant medical procedures

Recording of AEs
8.3.4
Telephone Contact 3 (Week 2/Day 9) [UCB7665 10mg/kg only]

Concomitant medications

Concomitant medical procedures

Recording of AEs
8.3.5
Telephone Contact 4 (Week 2/Day 10) [UCB7665 10mg/kg only]

Concomitant medications

Concomitant medical procedures

Recording of AEs
Change #62
8.3 Observation Period
The Observation Period will last for 8 weeks following the final dose administration. The first 
visit in the Observation Period will be performed 3 days after the final dose administration and 
subsequent visits will be performed at weekly intervals (except for a 2-week interval before the 
final visit). 
For UCB7665 4mg/kg dose, the following visits will be performed: Visit 8, Visit 9, Visit 10, 
Visit 11, Visit 12, Visit 13, Visit 14, and Visit 15, corresponding to UCB7665 7mg/kg Visit 6, 
Visit 7, Visit 8, Visit 9, Visit 10, Visit 11, Visit 12, and Visit 13.
Has been changed to:
8.4 Observation Period 
The Observation Period will last for 8 weeks following the final dose administration. The first 
visit in the Observation Period will be performed 3 days after the final dose administration and 
subsequent visits will be performed at weekly intervals (except for a 2-week interval before the 
final visit). 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 322 of 353
For UCB7665 4mg/kg weekly dose (Dose Arm 1), the following visits will be performed: 
Visit 8, Visit 9, Visit 10, Visit 11, Visit 12, Visit 13, Visit 14, and Visit 15, corresponding to 
UCB7665 7mg/kg weekly dose (Dose Arm 2) on Visit 6, Visit 7, Visit 8, Visit 9, Visit 10, 
Visit 11, Visit 12, and Visit 13.
For the UCB7665 10mg/kg weekly dose (Dose Arm 3), the following visits will be performed: 
Visit 5, Visit 6, Visit 7, Visit 8, Visit 9, Visit 10, Visit 11, and Visit 12.
For the UCB7665 15 mg/kg dose (Dose Arm 4) and the UCB7665 20mg/kg dose (Dose Arm 5), 
the following visits will be performed: Visit 3, Visit 4, Visit 5, Visit 6, Visit 7, Visit 8, Visit 9 
and Visit 10.
Change #63
8.3.1
Visit 8 (Week 5/Day 32) [UCB7665 4mg/kg]/ Visit 6 (Week 3/Day 18) [UCB7665 
7mg/kg]
…

Blood sample for the following laboratory parameters:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665 

Anti-UCB7665 antibodies/IgG depletion assay

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Serum biomarkers 

Serum total IgG and IgG subclasses concentration
…
Has been changed to:
8.4.1
Visit 8 (Week 5/Day 32) [UCB7665 4mg/kg]/ Visit 6 (Week 3/Day 18) [UCB7665 
7mg/kg]]/ Visit 5 (Week 2/Day 11) [UCB7665 10mg/kg]
Visit 3 (Week 1/Day 4) [UCB7665 15mg/kg and UCB7665 20mg/kg]

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665 

Anti-UCB7665 antibodies

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Exploratory safety biomarkers
only from 
subjects experiencing severe headaches or GI disturbances (only in case of Adverse 
Events of Interest, see Section 12.4)
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 323 of 353

Serum total IgG and IgG subclasses concentration
Change #64
8.3.2
Visit 9 (Week 6/Day 36) [UCB7665 4mg/kg]/ Visit 7 (Week 4/Day 22) [UCB7665 
7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
The following assessments will be performed at this visit:
…

12-lead ECG

Urine sample for urinalysis

Blood sample for the following laboratory parameters:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665

Anti-UCB7665 antibodies/IgG depletion assay

Serum biomarkers 

Serum total IgG and IgG subclasses concentration

Serum IgA, IgM, and IgE concentration 

ITP-specific autoantibodies
Has been changed to:
8.4.2
Visit 9 (Week 6/Day 36) [UCB7665 4mg/kg ]/ Visit 7 (Week 4/Day 22) [UCB7665 
7mg/kg]]/ Visit 6 (Week 3/Day 15) [UCB7665 10mg/kg]
Visit 4 (Week 2/Day 8) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the second visit in the Observation Period. A visit window of ±2 days is applicable for 
this visit relative to the day of the final dosing visit. The following assessments will be 
performed at this visit:
…

12-lead ECG (triplicate)
…

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Plasma concentration of UCB7665

Anti-UCB7665 antibodies
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 324 of 353

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety 
biomarkers)
Change #65
8.3.3
Visit 10 (Week 7/Day 43) [UCB7665 4mg/kg]/ Visit 8 (Week 5/Day 29) [UCB7665 
7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
This visit can be performed at home with a healthcare professional visiting the subject at his/her 
home. The following assessments will be performed at this visit:
…

Blood sample for the following laboratory parameters:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies/IgG depletion assay

Serum biomarkers 

Serum BAFF levels

Serum total IgG and IgG subclasses concentration
…
Has been changed to:
8.4.3
Visit 10 (Week 7/Day 43) [UCB7665 4mg/kg]/ Visit 8 (Week 5/Day 29) [UCB7665 
7mg/kg]]/ Visit 7 (Week 4/Day 22) [UCB7665 10mg/kg]
Visit 5 (Week 3/Day 15) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the third visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visi
…

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety 
biomarkers)
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 325 of 353

Serum BAFF levels

Exploratory biomarker analysis
…
Change #66
8.3.4
Visit 11 (Week 8/Day 50) [UCB7665 4mg/kg]/ Visit 9 (Week 6/Day 36) [UCB7665 
7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
The following assessments will be performed at this visit:
…

Blood sample for the following laboratory parameters:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Serum biomarkers 

Serum total IgG and IgG subclasses concentration
…
Has been changed to:
8.4.4
Visit 11 (Week 8/Day 50) [UCB7665 4mg/kg]/ Visit 9 (Week 6/Day 36) [UCB7665 
7mg/kg]]/ Visit 8 (Week 5/Day 29) [UCB7665 10mg/kg]
Visit 6 (Week 4/Day 22) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the fourth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. The following assessments will be performed at 
this visit:
…

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Exploratory safety biomarkers
Blood 
samples are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory
safety biomarkers)

Serum total IgG and IgG subclasses concentration 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 326 of 353
Change #67
8.3.5
Visit 12 (Week 9/Day 57) [UCB7665 4mg/kg]/ Visit 10 (Week 7/Day 43) [UCB7665 
7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
This visit can be performed at home with a healthcare professional visiting the subject at his/her 
home. The following assessments will be performed at this visit:
…

Blood sample for the following laboratory parameters:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies/IgG depletion assay

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Serum biomarkers 

Serum total IgG and IgG subclasses concentration
Has been changed to:
8.4.5
Visit 12 (Week 9/Day 57) [UCB7665 4mg/kg]/ 
Visit 10 (Week 7/Day 43) [UCB7665 7mg/kg]/ Visit 9 (Week 6/Day 36) [UCB7665 10mg/kg]
Visit 7 (Week 5/Day 29) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the fifth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visit:
…

12-lead ECG (triplicate)
…

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies

Serum complement levels (C3 and C4) and plasma complement levels (C3a and C5a)

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety 
biomarkers)

Serum total IgG and IgG subclasses concentration

Serum cytokines, only in case of late infusion reactions visible during the visit
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 327 of 353
Change #68
Visit 13 (Week 10/Day 64) [UCB7665 4mg/kg]/ Visit 11 (Week 8/Day 50) [UCB7665 7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
The following assessments will be performed at this visit:
…

Blood sample for the following laboratory parameters:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Serum total IgG and IgG subclasses concentration

Serum biomarkers 
…
Has been changed to:
8.4.6
Visit 13 (Week 10/Day 64) [UCB7665 4mg/kg]/ Visit 11 (Week 8/Day 50) [UCB7665 
7mg/kg]]/ Visit 10 (Week 7/Day 43) [UCB7665 10mg/kg]
Visit 8 (Week 6/Day 36) [UCB7665 15mg/kg and UCB7665 20mg/kg]
This is the sixth visit in the Observation Period. A visit window of ±2 days is applicable for this 
visit relative to the day of the final dosing visit. The following assessments will be performed at 
this visit:

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Serum total IgG and IgG subclasses concentration

Exploratory safety biomarker
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety 
biomarkers)
Change #69
8.3.7
Visit 14 (Week 11/Day 71) [UCB7665 4mg/kg]/ Visit 12 (Week 9/Day 57) [UCB7665 
7mg/kg]
A visit window of ±2 days is applicable for this visit relative to the day of the final dosing visit. 
This visit can be performed at home with a healthcare professional visiting the subject at his/her 
home. The following assessments will be performed at this visit:
Has been changed to:
8.3.7
Visit 14 (Week 11/Day 71) [UCB7665 4mg/kg]/ 
Visit 12 (Week 9/Day 57) [UCB7665 7mg/kg]/ Visit 11 (Week 8/Day 50) [UCB7665 10mg/kg]
Visit 9 (Week 7/Day 43) [UCB7665 15mg/kg and UCB7665 20mg/kg]
REDACTED COPY
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 328 of 353
This is the seventh visit in the Observation Period. A visit window of ±2 days is applicable for 
this visit relative to the day of the final dosing visit. This visit can be performed at home with a 
healthcare professional visiting the subject at his/her home. The following assessments will be 
performed at this visit:

Concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory
rate)

Recording of AEs

Urine sample for urinalysis

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies

Exploratory safety biomarkers
 Blood samples 
are taken prior to dosing, 2 and 4 hours after end of infusion for exploratory safety 
biomarkers)

Serum BAFF levels

Exploratory biomarker analysis
Change #70
8.3.8
End-of-Study Visit: Visit 15 (Week 13/Day 85) [UCB7665 4mg/kg]/ 
Visit 13 (Week 11/Day 71) [UCB7665 7mg/kg]
…

12-lead ECG

Urine pregnancy test for women of childbearing potential

Urine sample for urinalysis

Blood sample for the following laboratory parameters:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies/IgG depletion assay

Serum total IgG and IgG subclasses concentration

ITP-specific autoantibodies 

ITP bleeding scale
REDACTED COP
er end
COP
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aramet
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 329 of 353

NFI-MS

Subject exit interview 

Serum cytokines, only in case of infusion reactions

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.
Has been changed to:
8.4.8 End-of-Study Visit: Visit 15 (Week 13/Day 85) [UCB7665 4mg/kg]/ 
Visit 13 (Week 11/Day 71) [UCB7665 7mg/kg]/ 
Visit 12 (Week 10/Day 64) [UCB7665 10mg/kg]
Visit 10 (Week 9/Day 57) [UCB7665 15mg/kg and UCB7665 20mg/kg]
…

12-lead ECG (triplicate)
…

Blood sample for the following:

Standard safety laboratories: hematology including coagulation parameters, clinical 
chemistry

Anti-UCB7665 antibodies

Serum total IgG and IgG subclasses concentration

ITP-specific autoantibodies 

For all dose arms, collection of whole blood for exploratory RNA analyses

NFI-MS

Subject exit interview 

Serum cytokines, only in case of late infusion reactions visible during the visit

Headache questionnaire, only if subject experiences severe headaches, followed by a 
neurological assessment (including fundoscopy). Additionally, other diagnostic procedures 
including but not limited to CT scan, MRI and/or LP for CSF collection to be performed if 
indicated at the discretion of the investigator, considering the local guidelines for performing 
LP in subjects with ITP.

TB signs and symptoms questionnaire
Change #71
8.4 Early Withdrawal Visit
Paragraph #3
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 330 of 353
The assessments to be done at both the Early Withdrawal Visit as well as the End-of-Study Visit 
are the same as those at Visit 15 for the UCB7665 4mg/kg group or Visit 13 for the 
UCB7665 7mg/kg group, except for the subject exit interview which will be performed at the 
End-of-Study Visit only.
Has been changed to:
The assessments to be done at both the Early Withdrawal Visit as well as the End-of-Study Visit 
are the same as those at Visit 15 for the UCB7665 4mg/kg weekly (Dose Arm 1) group, Visit 13 
for the UCB7665 7mg/kg weekly (Dose Arm 2) group, Visit 12 for the UCB7665 10mg/kg 
weekly (Dose Arm 3) group, or Visit 10 for the UCB7665 15mg/kg (Dose Arm 4) and UCB7665 
20mg/kg (Dose Arm 5) groups, except for the subject exit interview which will be performed at 
the End-of-Study Visit only.
Change #72
9.1
Platelet counts
NEW bullet points added:

Baseline-corrected AUEC for platelet count calculated from Baseline to the end of study visit

Clinical Response: platelet count ≥30x109/L and at least 2-fold increase from Baseline value 
and absence of bleeding

Time to Clinical Response: time from starting treatment to achievement of Clinical Response

Duration of Clinical Response: measured from achievement of Clinical Response to loss of 
Clinical Response (loss of Clinical Response defined as platelet count <30x109/L or less than 
2-fold increase from Baseline platelet count or presence of bleeding)

Complete Clinical Response: platelet count ≥100x109/L and absence of bleeding

Time to Complete Clinical Response: time from starting treatment to achievement of 
Complete Clinical Response

Duration of Complete Clinical Response: measured from achievement of Complete Clinical 
Response to loss of Complete Clinical Response (loss of Complete Clinical Response defined 
as platelet count <100x109/L or presence of bleeding)

No Clinical Response: platelet count <30x109/L or less than 2-fold increase from Baseline or 
presence of bleeding
NEW paragraph added:
The clinical response variables will be assessed only for visits for which both platelet counts and 
the ITP bleeding score are assessed (with the exception of the confirmatory platelet assessments 
which may be obtained at any visit [scheduled or unscheduled] provided that they meet the 
criteria below). In order to define a clinical response, the platelet count must be confirmed on 2 
separate occasions at least 7 days apart (ie, the second assessment should be ≥168 hours after the 
first assessment). The time to response will be taken as the time to the first platelet assessment 
(obtained at the same time as the corresponding ITP bleeding score assessment). If the second 
assessment does not fulfill the required criteria for a clinical response, the subject will be 
considered as a nonresponder at the respective visits. In order to define a clinical response (or no 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 331 of 353
clinical response), the platelet count must be confirmed on 2 separate occasions; further details 
will be provided in the SAP. Absence of bleeding is indicated by Grade 0 for all domains of the 
SMOG. Presence of bleeding is indicated by a Grade of 1 or above, for at least one domain of the 
SMOG.
Change #73
9.1
Platelet counts
Refer to Section 14 for details of statistical analysis of these parameters.
Has been changed to:
Refer to Section 14 for details of statistical analysis of these variables.
Change #74
11 Assessment of other immunological variables
…

Serum biomarkers levels over time

Serum BAFF levels

Plasma anti-UCB7665 antibodies/IgG depletion assay 

Cytokines
Cytokine samples will be taken at Baseline Visit for all subjects. At subsequent visits, cytokine 
samples will be taken only when the subject experiences infusion reactions.
Has been changed to:
…

Serum BAFF levels

Lymphocyte counts (B and T)

Anti-UCB7665 antibodies

Cytokines
Cytokine samples will be taken at Baseline Visit for all subjects. At subsequent visits, cytokine 
samples will be taken only when the subject experiences infusion reactions.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 332 of 353
Change #75
12.1.1 Definition of adverse event 
Paragraph #4:
Bleeding events should not be reported as an AE since these events will be assessed and reported 
during the ITP-BAT assessment. Common Terminology Criteria for Adverse Events (CTCAE) 
grade 3 or more bleeding events should be reported as AEs. 
Has been changed to:
Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2 bleeding events 
should not be reported as an AE since these events will be assessed and reported during the 
ITP-BAT assessment; CTCAE grade 3 or more bleeding events should be reported as AEs.
Change #76
12.1.9 Safety signal detection
Paragraph #1:
The safety variables and ADA results available after 7 days of the final dose of 3 and 6 subjects 
in the UCB7665 4mg/kg dose arm will be reviewed by the DMC (interim analysis 1 and 2) 
comprising at least 1 external expert, the UCB study physician, the UCB PS representative, and a 
biostatistician and will be summarized on an ongoing basis during the study so as to 
continuously evaluate the safety of subjects. The DMC will meet and reach a decision on 
whether or not the study can continue as planned, and whether or not the next dose arm can be 
started. Subsequently, safety variables and ADA results available after 7 days of the final dose of 
3 and 6 subjects in the UCB7665 7mg/kg dose arm (together with all available data from the 
UCB7665 4 mg/kg dose arm) will be reviewed by the DMC (interim analysis 3 and 4).
Has been changed to:
The safety variables and ADA results available after 7 days of the final dose of 3 and 6 subjects 
in the UCB7665 4mg/kg weekly group (Dose Arm 1) will be reviewed by the DMC (interim 
analysis 1 and 2) comprising at least 1 external expert, the UCB study physician, the UCB PS 
representative, and a biostatistician and will be summarized on an ongoing basis during the study 
so as to continuously evaluate the safety of subjects. The DMC will meet and reach a decision on 
whether or not the study can continue as planned, and whether or not Dose Arm 2 can be started. 
Subsequently, safety variables and ADA results available after 7 days of the final dose of 3 and 
6 subjects in the UCB7665 7mg/kg weekly (Dose Arm 2) (together with all available data from 
Dose Arm 1 and 2) will be reviewed by the DMC (interim analysis 3 and 4). The DMC will also 
meet and review safety data to add additional subjects to subsequent dose arms or to open 
subsequent dose arms. Further details are described in Section 5.1
The DMC may also decide to reduce the number of doses in each of the dose arms, to stop a dose 
arm or not to open a dose arm based on review of data during the study.
Change #77
12.5
Immediate reporting of adverse events
The following AEs must be reported immediately:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 333 of 353

SAE: AE that the investigator classifies as serious by the above definitions regardless of 
causality

Suspected transmission of an infectious agent via a medicinal product

AE of special interest (see Section 12.3)

AE of interest (see Section 12.4)
Has been changed to:
The following AEs must be reported immediately using the SAE Report Form according to the 
procedure in Section 12.2.2:

SAE: AE that the investigator classifies as serious by the above definitions regardless of 
causality

Suspected transmission of an infectious agent via a medicinal product

AE of special interest (see Section 12.3)

AE of interest (see Section 12.4)

Confirmed LTB, active TB, and NTBI (see Section 12.8.1)
Change #78
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Coagulation 
parameters
Urinalysis
Pregnancy test
Basophilsa
Calcium
INR 
pH
Urineb HCG
Eosinophilsa
Phosphate
Prothrombin time
Protein
Serumc HCG
Neutrophilsa
Chloride
aPTT
Creatinine 
Lymphocytesa
Magnesium
Fibrinogen
Glucose
Others
Monocytesa
Potassium
Ketones
HbA1c
Hematocrit
Sodium
Urobilinogen
HIV
Hemoglobin
BUN
Bilirubin
Hepatitis B
(HBsAg, anti-HBs,
anti-HBc)
Platelet count
AST
Blood
Hepatitis C
(anti-HCV)
RBC count
ALT
Nitrite
WBC count
GGT
Albumin
B- and T-
Lymphocyte count
Total bilirubin 
Leucocytes
Direct bilirubin (if 
indicated)
REDACTED COPY 
O
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o the
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at
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 334 of 353
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Coagulation 
parameters
Urinalysis
Pregnancy test
LDH
Total cholesterol
Triglycerides
ALP
Total protein
Albumin
α1-globulin, 
α2-globulin, and 
β-globulin
Creatinine
hs-CRP
Amylase
ALP=alkaline phosphatase; ALT=alanine aminotransferase; anti-HBc=hepatitis B core antibody; anti-HBs=hepatitis 
B surface antibody; anti-HCV=hepatitis C virus antibody; aPTT=activated partial thromboplastin time; 
AST=aspartate aminotransferase; BUN=blood urea nitrogen;GGT=gamma-glutamyltransferase; 
HbA1c=glycosylated hemoglobin; HBsAg=hepatitis B surface antigen; HCG=human chorionic gonadotropin; 
HIV=human immunodeficiency virus; hs-CRP=high-sensitivity C-reactive protein; INR=International Normalized 
Ratio; LDH=lactate dehydrogenase; RBC=red blood cell; WBC=white blood cell 
a Absolute as well as percentages for the differential leucocyte counts will be performed.
b Urine pregnancy test will be performed predose on dosing days and at End-of-Study Visit.
c Serum pregnancy test is done at Visit 1 (Screening) and to confirm results of positive urine test if applicable.
DACTED COPY
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This document cannot be used to support any market
ening) a
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 335 of 353
Has been changed to:
Table 12‒2: Laboratory measurements
Hematology
Chemistry
Coagulation 
parameters
Urinalysis
Pregnancy test
Basophilsa
Calcium
INR 
pH
Urineb HCG
Eosinophilsa
Phosphate
Prothrombin time
Protein
Serum
c HCG
Neutrophilsa
Chloride
aPTT
Creatinine 
Lymphocytesa
Magnesium
Fibrinogen
Glucose
Others
Monocytesa
Potassium
Ketones
HbA1c
Hematocrit
Sodium
Urobilinogen
HIV
Hemoglobin
BUN
Bilirubin
Hepatitis B
(HBsAg, anti-HBs,
anti-HBc)
Platelet count
AST
Blood
Hepatitis C
(anti-HCV)
RBC count
ALT
Nitrite
Tuberculosisd
WBC count
GGT
Albumin
Total bilirubin 
Leucocytes
Safety Biomarkerse
Direct bilirubin (if 
indicated)
LDH
Total cholesterol
Triglycerides
ALP
Total protein
Albumin
α1-globulin, 
α2-globulin, 
β-globulin, γ-globulin
Creatinine
hs-CRP
Amylase
a Absolute as well as percentages for the differential leucocyte counts will be performed.
ALP=alkaline phosphatase; ALT=alanine aminotransferase; anti-HBc=hepatitis B core antibody; anti-HBs=hepatitis 
B surface antibody; anti-HCV=hepatitis C virus antibody; aPTT=activated partial thromboplastin time; 
AST=aspartate aminotransferase; BUN=blood urea nitrogen;GGT=gamma-glutamyltransferase; 
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 336 of 353
HbA1c=glycosylated hemoglobin; HBsAg=hepatitis B surface antigen; HCG=human chorionic gonadotropin; 
HIV=human immunodeficiency virus; hs-CRP=high-sensitivity C-reactive protein; INR=International Normalized 
Ratio; LDH=lactate dehydrogenase; RBC=red blood cell; WBC=white blood cell 
b Urine pregnancy test will be performed predose on dosing days and at End-of-Study Visit.
c Serum pregnancy test is done at Visit 1 (Screening) and to confirm results of positive urine test if applicable.
d Interferon-gamma release assay by central laboratory.
e May include but not limited to the biomarkers listed in the table. Samples collected for safety biomarkers at 
Baseline (Visit 2) and 4 hours post dosing (Visit 2) for all subjects and during follow up only in subjects with severe 
headache and/or moderate to severe GI disturbances. The Baseline samples will only be analysed in case he subject 
experienced a severe headache and/or moderate to severe GI disturbance
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 337 of 353
Change #79
Table 12-3: Required investigations and follow up for PDILI 
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivit
y
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consultc
Medical Monitor 
must be notified 
within 24 hours (eg, 
by laboratory alert) 
and subject discussed 
with Medical Monitor 
ASAP.
Immediate, 
permanent IMP 
discontinuation.
Essential: Must 
have repeat liver 
chemistry values 
and additional 
testing completed 
ASAP (see 
Section 12.7.1.3); 
recommended to 
occur at the site 
with HCP.
Monitoring of liver 
chemistry values at 
least twice per week 
until values 
normalize, stabilize, 
or return to within 
baseline values.d
≥8xULN
NA
NA
≥3xULN
NA
Yes
Immediate, 
temporary or 
permanent, IMP 
discontinuation.
≥3xULN 
(and ≥2x 
baseline) 
and 
<5xULN
<2xULN
No
Discussion with 
Medical Monitor 
required if the 
criterion that allows 
for IMP continuation 
is met.
Further investigation 
– immediate IMP 
discontinuation not 
required (see 
Section 12.7.1.2).
Not required unless
otherwise 
medically indicated 
(at discretion of 
investigator).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 338 of 353
Table 12-3: Required investigations and follow up for PDILI 
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivit
y
Consultation 
requirements
Actions
Testing
Evaluation
≥5xULN 
(and ≥2x 
baseline) 
<2xULN
No
Discussion with 
Medical Monitor 
required.
Immediate, 
permanent IMP 
discontinuation.
Essential: Every
attempt must be 
made to have 
repeat liver 
chemistry values 
and additional 
testing completed 
within 48 hours at 
the site with HCP 
(see 
Section 12.7.1.3).
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chemistry values at 
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until values 
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baseline values. d
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This document cannot be used to support any marketing au
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 339 of 353
Table 12-3: Required investigations and follow up for PDILI 
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivit
y
Consultation 
requirements
Actions
Testing
Evaluation
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; 
HCP=healthcare practitioner; IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; 
ULN=upper limit of normal
a
Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms 
include eosinophilia (>5%), rash, and fever (without clear alternative cause).
b
If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical 
Monitor.
c
Details provided in Section12.7.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment 
and management of potential hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d
Unless an alternative monitoring schedule is agreed by the investigator and UCB responsible physician. Determination of 
stabilization is at the discretion of the investigator in consultation with the hepatologist (as applicable) and UCB responsible 
physician, as needed.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 340 of 353
Has been changed to:
Table 12-3: Required investigations and follow up for PDILI 
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULN
b
NA
Hepatology consultc
Medical Monitor must 
be notified within 
24 hours (eg, by 
laboratory alert) and 
subject discussed with 
Medical Monitor ASAP.
Immediate, permanent 
IMP discontinuation.
Essential: Must have 
repeat liver chemistry 
values and additional 
testing completed 
ASAP (see 
Section 12.7.1.3); 
recommended to 
occur at the site with 
HCP.
Monitoring of liver 
chemistry values at least 
twice per week until 
values normalize, 
stabilize, or return to 
within Baseline values.d
≥3xULN
NA
Yes
Immediate, temporary 
or permanent, IMP 
discontinuation.
≥3xULN 
(and ≥2x 
Baseline) 
and 
<5xULN
<2xULN
No
Discussion with Medical 
Monitor required if the 
criterion that allows for 
IMP continuation is met.
Further investigation –
immediate IMP 
discontinuation not 
required (see 
Section 12.7.1.2).
Not required unless 
otherwise medically 
indicated (at 
discretion of 
investigator).
≥5xULN 
(and ≥2x 
Baseline) 
<2xULN
No
Discussion with Medical 
Monitor required. 
Hepatology consult 
required if ALT or AST 
≥8xULN.
Immediate, permanent 
IMP discontinuation.
Essential: Every 
attempt must be made 
to have repeat liver 
chemistry values and 
additional testing 
completed within 
48 hours at the site 
with HCP (see 
Section 12.7.1.3).
Monitoring of liver 
chemistry values at least 
twice per week until 
values normalize, 
stabilize, or return to 
within Baseline values. d
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 341 of 353
Table 12-3: Required investigations and follow up for PDILI 
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause).
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
c Details provided in Section 12.7.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of 
potential hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d Unless an alternative monitoring schedule is agreed by the investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
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This document cannot be used to support any marketing authorization
on


UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 342 of 353
Change #80
Section 12.8
Other safety measurements
NEW sections added:
12.8.1 Assessment and management of TB and TB risk factors
With the currently available data, TB is not considered as an important potential or identified risk 
for treatment with UCB7665. As immunomodulation may carry a risk of new or activation of 
latent TB, UCB has conservatively developed TB detection and management procedures taking 
into account the most current recommendations of international guidelines (2010 WHO) and 
most recent literature, covering any infection by the mycobacteria tuberculosis complex. 
Appropriate rigorous precautions are being taken within this protocol to monitor for the risk of 
TB infection prior to study entry and during the study (see Section 6.2.2 (Exclusion Criterion 
#25) and Section 6.4. Following are the key considerations of these procedures:
12.8.1.1
TB Tests at Screening
The interferon-gamma release assay (IGRA) and TB questionnaire are required as indicated in 
Schedule of Assessments. 

TB screening is mandatory both before study entry and during the conduct of the study. The 
preferred screening test is IGRA performed at a Central Laboratory. 
-
The IGRA result must be negative for subjects to enroll in this study
-
Subjects who test positive for IGRA test should be excluded from the study and 
referred for appropriate medical evaluation according to the local medical practice 
guidelines. 
-
If the result of the IGRA test is indeterminate, the particular IGRA test previously
performed may be repeated once; if positive or indeterminate on retest, the subject 
may not be randomized to study drug and, if already randomized, must undergo 
appropriate study specified withdrawal procedures. The retest must be done during 
the protocol-defined Screening window.
12.8.1.2
Monitoring for TB during the study
Subjects will be monitored for signs/symptoms of TB using routine pharmacovigilance measures 
for Adverse Events. Subjects reporting AEs related to signs/symptoms of TB will be evaluated 
for LTB and active TB according to the local medical practice guidelines. 
Subjects with confirmed LTB or active TB or NTMBI infection will be immediately withdrawn 
from the study as described in Withdrawal Criteria. Confirmed LTB, active TB and NTMBI 
must be reported to the Sponsor immediately regardless of seriousness using the SAE Report 
Form. Additional information received by the Investigator should be provided within 24 hours of 
awareness.
Once withdrawn from study treatment, subjects should return for the POET, complete all early
withdrawal assessments, and complete the follow-up visits.
12.8.1.3
TB tests at Final /End of Study Visit
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 343 of 353
Subjects will be evaluated for signs and symptoms of latent or active TB infection and for risk 
factors of exposure to TB, using the TB questionnaire, at the Final /End of Study (EOS) Visit. 
See the ‘TB signs and symptoms questionnaire’ section for further instructions on using the 
questionnaire.
12.8.1.4
Signs and symptoms of Tuberculosis
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the subject’s history. 
Common symptoms with which the subject may present with include cough, blood in sputum, 
night sweats, lymphadenitis, joint pain/swelling, spinal deformity, headache/confusion, 
abdominal pain mimicking inflammatory bowel disease, frequent or painful urination, scrotal 
mass in men and pelvic inflammatory disease in women as well as other symptoms, or 
nonspecific symptoms. This is not an exhaustive list and unusual presentations should always be 
considered.
12.8.1.4.1 TB signs and symptoms questionnaire
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will assist with the identification of subjects who may
require therapy for TB. A subject who answers “Yes” to the question 
 at Screening is excluded. A “Yes” response to any of the other questions within the 
questionnaire at Screening should trigger further careful assessment to determine if subject has 
latent or active TB (see Section 6.2.2 (Exclusion Criterion #25). A “Yes” response to any of the 
questions during/end of the study should trigger further assessments as per local medical 
guidelines to determine if the subject has either LTB or active TB infection.
12.8.1.4.2 LTB infection, active TB or other NTMBI identified during study
During the study, subjects who develop evidence of LTB infection or active TB or NTMBI must 
immediately stop further administration of study drug and will be referred to an appropriate 
medical specialist for further evaluation.
Confirmed LTB or active TB or NTMBI must be reported to the Sponsor immediately as 
described above.
Change #81
Section 12.8.5 12-Lead ECG
Paragraph #1:
A standard 12-lead ECG will be performed at visits as specified in the schedule of study
assessments (Section5.2). Care should be taken to assure proper lead placement and quality ECG 
recordings. Subjects should rest in a supine position in a controlled, calm environment for at 
least 15 minutes prior to the recording and should be motionless during the recording. The ECG 
will be performed in triplicate prior to blood collection for assessment of laboratory parameters.
Has been changed to:
A standard 12-lead ECG will be performed at visits as specified in the schedule of study
assessments (Section 5.2). Care should be taken to assure proper lead placement and quality 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 344 of 353
ECG recordings. Subjects should rest in a supine position in a controlled, calm environment for 
at least 15 minutes prior to the recording and should be motionless during the recording. 
NEW paragraph #2 added:
The ECG will be performed in triplicate prior to blood collection for assessment of laboratory
parameters. Three ECGs should be recorded in a time frame of 5 minutes with at least 1 minute 
difference, 1-2 minutes between the ECGs.
Change #82
Section 14.1 Definition of analysis sets 
Paragraph #4:
The analysis of the PD, efficacy, and immunologic variables will be performed on the FAS. 
Selected outputs may be repeated for the Per Protocol Set (PPS). Further details will be provided 
in the SAP.
Paragraph #5 and #6:
Per Protocol Set:
The PPS is a subset of the FAS, consisting of those subjects who had received all foreseen sc 
infusions, had a platelet count measurement during the Observation Period, and no important 
protocol deviations that may potentially affect the platelet count as confirmed during a 
pre-analysis review of the data prior to database lock. Protocol deviations may not necessarily
lead to total exclusion of a subject from the PPS but may lead to exclusion of specific data. 
Pharmacokinetic Per Protocol Set (PK-PPS):
The PK-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations potentially affecting the plasma concentration of UCB7665, as confirmed during a 
pre-analysis review of the data prior to database lock.
Has been changed to:
The analysis of the PD (excluding total IgG, and IgG subclasses), efficacy, and immunologic 
variables will be performed on the FAS. Selected outputs may be repeated for the PD Per 
Protocol Set (PD-PPS). Further details will be provided in the SAP.
Pharmacokinetic Per Protocol Set (PK-PPS):
The PK-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations potentially affecting the plasma concentration of UCB7665, as confirmed during a 
pre-analysis review of the data prior to database lock. Protocol deviations may not necessarily
lead to total exclusion of a subject from the PK-PPS but may lead to exclusion of specific data.
Pharmacodynamic Per Protocol Set (PD-PPS)
The PD-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations potentially affecting the serum concentration of total IgG, as confirmed during a 
pre-analysis review of the data prior to database lock. Protocol deviations may not necessarily
lead to total exclusion of a subject from the PD-PPS but may lead to exclusion of specific data.
The PD-PPS will be used for the analysis of the total IgG, and IgG subclasses.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 345 of 353
Change #83
Section 14.3.2 Other safety analysis 
Paragraphs #1 and #2:
The absolute and relative frequencies for subjects with a given TEAE with respect to the 
preferred term according to the latest available version of the MedDRA, as well as the absolute 
frequencies of the individual TEAEs that have occurred, will be determined within each system 
organ class. Additional tables will summarize TEAEs by maximum intensity and causal 
relationship with UCB7665, as judged by the investigator. Adverse events will be categorized by
severity according to the CTCAE version 4.03 grading. In case the CTCAE grading is not 
available, the intensity (mild/moderate/severe) will be utilized. The TEAEs leading to 
discontinuation of IMP and treatment-emergent SAEs will also be summarized. The action taken, 
time of onset relative to dosing, and duration of each AE will be listed only.
For the continuous laboratory variables, the values and changes from Baseline will be 
summarized at each time point. For categorized values according to the reference range, shift 
tables from Baseline to each post-Baseline time point will be presented for selected variables to
be defined in the SAP. Values outside the reference range will be flagged in the data listings.
Has been changed to:
The absolute and relative frequencies for subjects with a given TEAE with respect to the 
preferred term according to the latest available version of the MedDRA, as well as the absolute 
frequencies of the individual TEAEs that have occurred, will be determined within each system 
organ class. Additional tables will summarize TEAEs by maximum intensity and causal 
relationship with UCB7665, as judged by the investigator. Adverse events will be categorized by 
severity according to the CTCAE version 4.03 grading. In case the CTCAE grading is not 
available, the intensity (mild/moderate/severe) will be utilized. For the purpose of the tabulations 
CTCAE grades will be aligned with the intensity classifications (mild/moderate/severe) to enable 
pooling of the AEs in the summaries. The TEAEs leading to discontinuation of IMP and 
treatment-emergent SAEs will also be summarized. The action taken, time of onset relative to 
dosing, and duration of each AE will be listed only.
For the continuous laboratory variables, the values and changes from Baseline will be 
summarized at each time point. For categorized values according to the reference range, shift 
tables from Baseline to each post-Baseline time point will be presented for selected variables to 
be defined in the SAP. Values outside the reference range will be flagged in the data listings. The 
number and percentage of subjects with markedly abnormal laboratory results (based on CTCAE 
grading) will be tabulated for each dose arm.
Change #84
Section 14.4.1 Efficacy analysis 
The main efficacy variable is the maximum increase from Baseline in platelet count during the 
study. The maximum increase from Baseline and maximum platelet count during the study will 
be summarized by dose arm.
In addition, all measurements of platelet count will be summarized by dose arm and time point 
using descriptive statistics (including changes from Baseline).
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 346 of 353
For each dose arm a 1-sided t-test will be applied to assess if the average maximum increase 
from Baseline is greater than zero. In case the assumptions for the-t-test are not fulfilled a 
variance-stabilizing transformation may be applied in addition and/or an alternative 
nonparametric method may be considered. Further details will be provided in the SAP.
The Response rate, Complete Response rates, and platelet count ≥50x109/L will be summarized 
(number of subjects and percentages) and presented with 90% 2-sided confidence intervals for 
the rate of responders at each time point and overall (across all time points). Response and 
Complete Response are defined in Section 4.2.
Time to Response, time to Complete Response, time to platelet count ≥50x109/L, duration of 
Response, duration of Complete Response, and duration of platelet count ≥50x109/L will be 
calculated and summarized by dose arm.
The results from the ITP bleeding scale will be summarized at each time point and will include 
the grades for each of the 3 major domains: skin (S), visible mucosae (M), and organs (O). 
Results of the NFI-MS will be summarized at each time point, using summary scores where 
applicable. Changes from Baseline will be calculated and summarized.
Has been changed to:
The main efficacy variable is the maximum increase from Baseline in platelet count during the 
study. The maximum increase from Baseline and maximum platelet count during the study will 
be summarized by dose arm.
In addition, all measurements of platelet count will be summarized by dose arm and time point 
using descriptive statistics (including changes from Baseline).
For dose arms with ≥10 subjects, a 1-sided t-test will be applied to assess if the average 
maximum increase from Baseline is greater than zero. In case the assumptions for the-t-test are 
not fulfilled, an alternative nonparametric method may be considered. Further details will be 
provided in the SAP. The Response, Complete Response, and platelet count ≥50x109/L will be 
summarized (number of subjects and percentages) and presented with 90% 2-sided confidence 
intervals for the rate of responders at each time point and overall (across all time points). 
Response and Complete Response are defined in Section 4.3. The analysis will be repeated for 
the Clinical Response variables defined in Section 4.3.
Time to Response, time to Complete Response, time to platelet count ≥50x109/L, duration of 
Response, duration of Complete Response, duration of platelet count ≥50x109/L, and 
Baseline-corrected AUEC for platelet count will be calculated and summarized by dose arm. The 
time to first response will be analyzed using a log-rank test and displayed using Kaplan-Meier 
curves. The time to Response, time to Complete Response, and respective durations will be 
summarized by dose arm.
The results from the ITP bleeding scale will be summarized at each time point and will include 
the grades for each of the 3 major domains: skin (S), visible mucosae (M), and organs (O). In 
addition the number and percentage of subjects with severe or clinically relevant bleeding and 
number and percentage of subjects with absence of bleeding will be summarized at each time 
point.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 347 of 353
Results of the NFI-MS will be summarized at each time point, using summary scores where 
applicable. Changes from Baseline will be calculated and summarized.
Additional subgroup analyses may be performed as needed and further details will be provided in 
SAP regarding these analyses.
Change #85
Section 14.4.3 Pharmacodynamic analysis 
For all PD variables, descriptive statistics for the values and change from Baseline and/or 
percentage change from Baseline will be tabulated by time point. If appropriate, measurements 
will be log-transformed.
The PD variables will include ITP-specific autoantibodies
total IgG, and IgG subclasses. In addition, for total IgG, the maximum decrease from Baseline 
and minimum value will be evaluated and summarized. Figures of mean values over time and 
changes from Baseline will be presented.
Has been changed to:
For all PD variables, descriptive statistics for the values and change from Baseline and/or 
percentage change from Baseline will be tabulated by time point. 
The PD variables will include ITP-specific autoantibodies 
total IgG, and IgG subclasses. In addition, for total IgG, the maximum decrease from Baseline 
and minimum value will be evaluated and summarized. Figures of mean values over time and 
changes from Baseline will be presented.
Change #86
Section 14.4.4 Immunologic variables 
Paragraphs #1 and #2:
All immunologic variables including concentrations of immunoglobulins (IgA, IgE, and IgM),
serum (C3 and C4) and plasma (C3a and C5a) complement levels, serum biomarkers 
 
 serum BAFF levels and the results of 
the IgG depletion assay will be summarized by dose arm over time (including changes from 
Baseline) using descriptive statistics. Figures of mean values over time and changes from 
Baseline may be presented.
The ADA status (negative/positive) and changes in relative mass units from Baseline will be 
summarized by dose arm; figures will also be presented.
Has been changed to:
All immunologic variables including concentrations of immunoglobulins (IgA, IgE, and IgM), 
serum (C3 and C4) and plasma (C3a and C5a) complement levels, serum BAFF levels, and 
lymphocyte counts (B and T) will be summarized by dose arm over time (including changes 
from Baseline) using descriptive statistics. Figures of mean values over time and changes from 
Baseline may be presented.
The ADA status (negative/positive) will be summarized by dose arm at each visit and overall; 
figures will also be presented in conjunction with PK concentrations of UCB7665.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 348 of 353
Change #87
14.4.5.2
Subject characteristics 
Bullet point #3:

Prior and concomitant medications
Has been changed to:

Past, prior, and concomitant medications
Change #88
Section 14.7 Planned interim analysis and data monitoring 
Paragraph #2:
For the sequential adaptive design in this study, at least 4 interim analyses will be performed. 
Safety data from the interim analyses will be reviewed by the DMC to monitor the safety, to 
adapt the dose regimen, and to decide when and if the UCB7665 7mg/kg dose arm should be 
opened. Planned dosing may be discontinued for all subjects on a dose arm (see Section 6.5).
Paragraph #4:
If the study continues without modifications, the next interim analysis will take place after data 
from 3 additional subjects are available. Based on the available combined data of the first 6 
subjects, the DMC will decide if the 3x7mg/kg dose arm can be initiated. If the new dose arm 
will be initiated and if the 5x4mg/kg will be continued, new subjects will be randomized to 1 of 
the 2 dose arms in an allocation ratio of 1:1 (Once 15 subjects are in the 4mg/kg group, the 
remaining subjects will not be randomized. They will be allocated to the 7mg/kg group).
Paragraph #7:
The fourth interim analysis and review of data by DMC will take place after safety data (7 days 
after final dose) is available for the first 6 subjects in Dose Arm 2.
The timing of further interim analysis and review of data by DMC will be decided by the DMC 
members at the fourth DMC meeting.
Paragraph #8:
During these reviews recruitment in the dose arms will not be stopped. If needed, subsequent 
DMC meetings may take place and the frequency will be detailed in the DMC charter.
Paragraph #9:
The DMC will monitor data for all reported AEs, clinical findings, including vital signs (pulse 
rate, blood pressure, temperature, and respiratory rate) and safety laboratory values, and 
immunogenicity data. Pharmacokinetic data will not be required for DMC review as blood 
sampling will be performed at a single time point per visit only. Thus, PK data is restricted only 
to the concentration data and can therefore make no plausible contribution to the assessment of 
safety in this particular study.
Paragraph #12:
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 349 of 353
A detailed description of the DMC composition, processes and responsibilities, criteria to 
escalate to the next dose arm, and criteria to stop a dose arm will be provided in a separate DMC 
charter.
Has been changed to:
Paragraph #2:
For the sequential adaptive design in this study, at least 11 interim analyses will be performed. 
Safety data from the interim analyses will be reviewed by the DMC to monitor the safety, to 
adapt the dose regimen, and to decide when and if the UCB7665 7mg/kg weekly group (Dose 
Arm 2), UCB7665 10mg/kg weekly group (Dose Arm 3), UCB7665 15mg/kg group (Dose 
Arm 4) and UCB7665 20mg/kg group (Dose Arm 5) should be opened. Planned dosing may be 
discontinued for all subjects in a dose arm (see Section 6.5).
Paragraph #4:
If the study continues without modifications, the next interim analysis will take place after data 
from 3 additional subjects are available. Based on the available combined data of the first 
6 subjects, the DMC will decide if the 3x7mg/kg dose arm can be initiated. If the new dose arm 
will be initiated and if the 5x4mg/kg will be continued, new subjects will be randomly assigned 
to 1 of the 2 dose arms in an allocation ratio of 1:1
Paragraphs #6 and #7:
The fourth planned interim analysis and review of data by DMC will take place after safety data 
(7 days after final dose) is available for the first 6 subjects in Dose Arm 2.
All subsequent DMC meetings will be dependent on opening of Dose Arms 3, 4 and 5 and 
decisions of the previous DMC meetings. Review of data will occur after every 3 subjects. More 
details are included in the DMC charter.
Paragraph #8:
During the first three interim analyses, recruitment in the Dose Arms 1 and 2 will not be stopped. 
If needed, subsequent DMC meetings may take place and the frequency will be detailed in the 
DMC charter.
Paragraph #11:
A detailed description of the DMC composition, processes and responsibilities, criteria to 
escalate to the next dose arm, and criteria to stop, or continue a dose arm will be provided in a 
separate DMC charter.
Change #89
Section 14.8 Determination of sample size 
Paragraph s#1 and #2
The sample size of 15 subjects, in each dose arm, is mainly based on the efficacy objective of the 
study. In addition the 2x15 subjects ensure that sufficient data are available to form conclusions 
about the safety of administering UCB7665.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 350 of 353
An approximate sample size calculation for the efficacy variable “maximum increase from 
Baseline in platelet count” shows that 15 subjects would be sufficient to show a change from 
Baseline with 1-sided testing at 5% and power of 80%. The anticipated change is based on an 
assumed Baseline average of 25x109/L and a clinically meaningful maximum value of 
100x109/L. The calculation made use of platelet count data presented in a publication by
Robak T (Robak et al, 2009), but it is approximate as maximum changes from Baseline for 
individual subjects were not available, necessitating the use of the maximum average platelet 
count instead. The SD is taken from visual inspection.
Has been changed to:
The sample size of 15 subjects in Dose Arms 1 and 2, is mainly based on the efficacy objective 
of the study. In addition the 15 subjects in Dose Arms 1 and 2 ensure that sufficient data are 
available to form conclusions about the safety of administering UCB7665. Based on the safety 
data from dose arms 1 and 2, the sample size of 6 to 12 subjects in Dose Arms 3, 4 and 5 is 
judged to be sufficient in order to explore subjects’ safety and IgG reductions under different 
dose regimens and is not based on a formal sample size calculation. 
For Dose Arms 1 and 2, an approximate sample size calculation for the efficacy variable 
“maximum increase from Baseline in platelet count” shows that 15 subjects would be sufficient 
to show a change from Baseline with 1-sided testing at 5% and power of 80%. The anticipated 
change is based on an assumed Baseline average of 25x109/L and a clinically meaningful 
maximum value of 100x109/L. The calculation made use of platelet count data presented in a 
publication by Robak T (Robak et al, 2009), but it is approximate as maximum changes from 
Baseline for individual subjects were not available, necessitating the use of the maximum 
average platelet count instead. The SD is taken from visual inspection.
Change #90
Section 15.1 Informed consent 
NEW paragraph added:
Subjects have the right to withdraw their consent for the exploratory genomic substudy at any 
point without any impact on their care or participation in the main study. In this case, any data 
already generated on the samples will be retained and used, but no further analysis will occur.
Change #91
Section 15.4 Subject privacy
NEW paragraphs added:
Genetic analysis data will not be shared with the subjects and will be subject to the highest level 
of data protection, as per European regulations.
Samples may be shared with collaborators working within UCB and may be analyzed at a third 
party site, but only in relation to the aims of this exploratory analysis as detailed in this study
protocol. Samples may be stored for up to 20 years and maybe used at any time up to that point. 
Samples will remain under the control of UCB at all times and may be destroyed at any point 
before the 20 year expiration date.
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 351 of 353
Change #92
Section 17 References
NEW reference:
Johnsen J. Pathogenesis in immune thrombocytopenia: new insights. Hematology Am Soc 
Hematol Educ Program. 2012;2012:306-12.
REDACTED COPY 
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 352 of 353
19
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Investigator:
Printed name
Date/Signature
REDACTED COPY 
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Y
plication and any extensions or variations thereof.
treated
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ion by
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e/Signa
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UCB
15 Feb 2017
Clinical Study Protocol
UCB7665
TP0001
Confidential
Page 353 of 353
20
SPONSOR DECLARATION
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.


ELECTRONIC SIGNATURES
Signed by 
Meaning of Signature 
Server Approval Date 
(dd-mon-yyyy 
(HH:mm)) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TP0001-Protocol Amendment 3 A multicenter, open-label,
multiple-dose study to evaluate the safety, tolerability, and efficacy
of UCB7665 in subjects
Clinical Approval
16-Feb-2017 15:58 GMT+01
Clinical Approval
17-Feb-2017 13:51 GMT+01
Clinical Approval
17-Feb-2017 14:34 GMT+01
D COPY 
D C
REDACTE
DA
proval
TED
proval
y marketing authorization application and any extensions or variations thereof.
n a
any e
rver A
any 
rver A
nd an
(d
a
(d
n and
y e
n a
uth
et
This document cannot be used to support any
pp
d
16
n
16
r

SAP_001.pdf: 
UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 1 of 128
STATISTICAL ANALYSIS PLAN AMENDMENT 3
Study: TP0001
Product: UCB7665
A MULTICENTER, OPEN-LABEL, MULTIPLE DOSE STUDY TO EVALUATE THE 
SAFETY, TOLERABILITY AND EFFICACY OF UCB7665 IN SUBJECTS WITH PRIMARY 
IMMUNE THROMBOCYTOPENIA
SAP/Amendment Number
Date
Final SAP
07 Oct 2016
SAP Amendment 1
14 Nov 2017
SAP Amendment 2
14 May 2018
SAP Amendment 3
28 Jan 2019
Confidentiality Statement
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
REDACTED COPY 
IPLE 
D CO
IPLE 
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ED 
Y OF
HROM
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HROM
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.
DOSE
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DOSE
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UCB7
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horiz
MBOC
Oct
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Oct 20
ar
20
14 No
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14 No
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14
an
4


UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 2 of 128
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................7
1
INTRODUCTION ...........................................................................................................12
2
PROTOCOL SUMMARY...............................................................................................13
2.1
Study objectives...........................................................................................................13
2.1.1
Primary objective.................................................................................................13
2.1.2
Secondary objectives ...........................................................................................13
2.1.3
Exploratory objectives.........................................................................................13
2.2
Study variables.............................................................................................................14
2.2.1
Safety variables....................................................................................................14
2.2.1.1
Primary safety variable..............................................................................14
2.2.1.2
Other safety variables................................................................................14
2.2.2
Efficacy variables ................................................................................................14
2.2.3
Pharmacokinetic and pharmacodynamic variables..............................................16
2.2.3.1
Pharmacokinetic variable ..........................................................................16
2.2.3.2
Pharmacodynamic variables......................................................................16
2.2.4
Other immunological variables............................................................................16
2.3
Study design and conduct ............................................................................................17
2.4
Determination of sample size.......................................................................................19
3
DATA ANALYSIS CONSIDERATIONS......................................................................19
3.1
General presentation of summaries and analyses ........................................................19
3.2
General study level definitions ....................................................................................21
3.2.1
Analysis timepoints .............................................................................................21
3.2.1.1
Relative day...............................................................................................21
3.2.1.2
Study periods.............................................................................................21
3.3
Definition of Baseline values.......................................................................................21
3.4
Protocol deviations.......................................................................................................23
3.5
Analysis sets.................................................................................................................23
3.5.1
Enrolled Set .........................................................................................................23
3.5.2
Safety Set.............................................................................................................23
3.5.3
Full Analysis Set..................................................................................................23
3.5.4
Per Protocol Set ...................................................................................................23
3.5.5
Pharmacokinetic Per Protocol Set .......................................................................24
3.5.6
Pharmacodynamic Per Protocol Set.....................................................................24
3.6
Treatment assignment and treatment groups ...............................................................24
3.7
Center pooling strategy................................................................................................24
3.8
Coding dictionaries ......................................................................................................24
3.9
Changes to protocol-defined analyses .........................................................................24
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 3 of 128
4
STATISTICAL/ANALYTICAL ISSUES.......................................................................25
4.1
Adjustments for covariates ..........................................................................................25
4.2
Handling of dropouts or missing data..........................................................................25
4.2.1
Efficacy data ........................................................................................................25
4.2.2
Safety laboratory data..........................................................................................25
4.2.3
Pharmacodynamic data........................................................................................25
4.2.4
Immunological data .............................................................................................25
4.2.5
UCB7665 concentration data...............................................................................25
4.2.6
Electrocardiogram data........................................................................................26
4.2.7
Dates and times....................................................................................................26
4.3
Handling of repeated and unscheduled measurements ................................................28
4.4
Interim analyses and data monitoring..........................................................................28
4.5
Multicenter studies.......................................................................................................29
4.6
Multiple comparisons/multiplicity...............................................................................29
4.7
Active-control studies intended to show equivalence..................................................29
4.8
Examination of subgroups ...........................................................................................29
5
STUDY POPULATION CHARACTERISTICS.............................................................30
5.1
Subject disposition.......................................................................................................30
5.2
Protocol deviations.......................................................................................................30
6
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................31
6.1
Demographics ..............................................................................................................31
6.2
Other Baseline characteristics......................................................................................31
6.3
Medical history and concomitant diseases...................................................................32
6.4
Past, prior, baseline and concomitant medications ......................................................32
6.4.1
Past medication definition ...................................................................................33
6.4.2
Prior medication definition..................................................................................33
6.4.3
Baseline medication definition ............................................................................33
6.4.4
Concomitant medication definition .....................................................................33
7
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................33
8
EFFICACY ANALYSES ................................................................................................33
8.1
Platelets........................................................................................................................33
8.1.1
Definition of variables .........................................................................................34
8.1.2
Presentation of results..........................................................................................35
8.1.3
Statistical analysis of platelets.............................................................................37
8.1.3.1
Analysis of maximum increase from Baseline..........................................37
8.1.3.2
Analysis of time to response......................................................................37
8.1.3.3
Analysis of responder rate.........................................................................37
8.1.4
Rescue medication definition (after medical inspection) ....................................38
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8.2
Other efficacy variables ...............................................................................................38
8.2.1
ITP bleeding score ...............................................................................................38
8.2.1.1
ITP bleeding score and platelet response ..................................................39
8.2.2
Patient reported outcomes....................................................................................41
8.2.2.1
NFI-MS .....................................................................................................41
9
PHARMACOKINETICS AND PHARMACODYNAMICS..........................................42
9.1
Pharmacokinetics .........................................................................................................42
9.2
Pharmacodynamics ......................................................................................................43
9.2.1
ITP-specific autoantibodies .................................................................................43
9.2.2
Total IgG and IgG subclasses..............................................................................44
9.3
Other immunological variables....................................................................................45
9.3.1
Serum immunoglobulins and lymphocytes .........................................................45
9.3.2
Serum and plasma complement levels.................................................................45
9.3.3
Serum biomarkers................................................................................................45
9.3.4
Anti-drug antibodies ............................................................................................46
9.3.5
Cytokines .............................................................................................................47
10
SAFETY ANALYSES.....................................................................................................47
10.1
Extent of exposure .......................................................................................................48
10.2
Adverse events.............................................................................................................48
10.3
Clinical laboratory evaluations ....................................................................................50
10.3.1
Potential drug-induced liver injury......................................................................52
10.4
Vital signs, physical findings, and other observations related to safety......................53
10.4.1
Vital signs ............................................................................................................53
10.4.2
Electrocardiograms..............................................................................................54
10.4.3
Other safety variables ..........................................................................................55
11
OTHER ANALYSES ......................................................................................................55
12
REFERENCES ................................................................................................................57
13
APPENDICES .................................................................................................................58
13.1
Corticosteroid use ........................................................................................................58
13.2
NFI-MS........................................................................................................................58
13.3
ITP bleeding score .......................................................................................................59
13.4
Cytokines .....................................................................................................................71
13.5
Classification of markedly abnormal laboratory values based on CTCAE grades......72
13.6
Treatment group assignment for the TFLs...................................................................74
14
AMENDMENTS TO THE STATISTICAL ANALYSIS PLAN....................................76
14.1
Amendment 1...............................................................................................................76
14.1.1
Rationale for the amendment...............................................................................76
14.1.2
List of changes.....................................................................................................76
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14.2
Amendment 2.............................................................................................................102
14.2.1
Rationale for the amendment.............................................................................102
14.2.2
List of changes...................................................................................................102
14.3
Amendment 3.............................................................................................................114
14.3.1
Rationale for the amendment.............................................................................114
14.3.2
List of changes...................................................................................................114
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE...................................................128
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28 Jan 2019
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TP0001
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Page 6 of 128
LIST OF TABLES
Table 3‒1:
Definition of Baseline......................................................................................22
Table 4‒1:
Calculation rules for duration of adverse events..............................................27
Table 10‒1:
Clinical laboratory measurements....................................................................51
Table 10‒2:
TEMA/PCS criteria for vital signs...................................................................53
Table 10‒3:
TEMA/PCS criteria for ECG...........................................................................55
Table 13‒1:
ITP-BAT scoring .............................................................................................61
Table 13‒2:
Criteria for markedly abnormal laboratory tests..............................................72
Table 13‒3:
Treatment group assignment for the tabulations..............................................74
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LIST OF ABBREVIATIONS
ACP
above cutpoint
ADA
anti-drug antibody
ADaM
analysis data model
AE
adverse event
ALC
absolute lymphocyte count
ALD
above the limit of detection
ALP
alkaline phosphatase
ALQ
above the limit of quantification
ALT
alanine aminotransferase
ANC
absolute neutrophil count
anti-HBc
hepatitis B core antibody
anti-HBs
hepatitis B surface antibody
anti-HCV
hepatitis C virus antibody
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
AUEC
area under the effect curve
BAFF
B cell activating factor
BCP
below cutpoint
BLQ
below the limit of quantification
BMI
body mass index
BUN
blood urea nitrogen
CI
confidence interval
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28 Jan 2019
Statistical Analysis Plan
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TP0001
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CP
confirmed positive
CRF
case report form
CRO
contract research organization
CSF
cerebrospinal fluid
CSR
Clinical Study Report
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
DEM
data evaluation meeting
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
ES
Enrolled Set
EudraCT
European Union Drug Regulating Authorities 
Clinical Trials
EOS
end of study
EW
early withdrawal
FAS
Full Analysis Set
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
geoCV
geometric coefficient of variation
geoMean
geometric mean
GGT
gamma glutamyltransferase
GM-CSF
granulocyte-macrophage colony-stimulating factor
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H0
null hypothesis
H1
alternative hypothesis
HA
high abundance
HbA1c
glycosylated hemoglobin
HBsAg
hepatitis B surface antigen
HCG
human chorionic gonadotropin
HIV
human immunodeficiency virus
HLT
high level term
hsCRP
high sensitivity C-reactive protein
ICAM-1
intercellular adhesion molecule-1
ICH
International Council for Harmonisation (formerly 
referred to as International Conference on 
Harmonisation)
IFN
interferon
Ig
immunoglobulin
IL
interleukin
INR
international normalized ratio
ITP
primary immune thrombocytopenia
ITP-BAT
ITP-specific Bleeding Assessment Tool
IVIg
intravenous immunoglobulin
IXRS
interactive voice/web response system
LDH
lactate dehydrogenase
LLOQ
lower limit of quantification
LP
lumbar puncture
MCP
monocyte chemotactic protein
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TP0001
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MDC
macrophage-derived chemokine
MedDRA
Medical Dictionary for Regulatory Activities
MIP
macrophage inflammatory protein
MRI
magnetic resonance imaging
n
number of subjects
NCP
not confirmed positive
NFI-MS
Neurological Fatigue Index for Multiple Sclerosis
OD
optical density
PCS
potentially clinically significant
PD
pharmacodynamic
PDILI
potential drug-induced liver injury
PD-PPS
Pharmacodynamic Per Protocol Set
PK
pharmacokinetic
PK-PPS
Pharmacokinetic Per Protocol Set
PPS
Per Protocol Set
PT
preferred term
QWK
every week 
QTcF
QT corrected for heart rate using Fridericia’s 
formula
RBC
red blood cells
RMU
relative mass units
RNA
ribonucleic acid
SAP
Statistical Analysis Plan
sc
subcutaneous
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SD
standard deviation
SMOG
Skin (S), visible mucosae (M) and organs (O), with 
gradation of severity
SOC
system organ class
SS
Safety Set
TARC
thymus and activation-related chemokine
TB
tuberculosis
TEAE
treatment-emergent adverse event
TEMA
treatment-emergent markedly abnormal
TFLs
tables, figures and listings
TGFβ
transforming growth factor beta
TNF
tumor necrosis factor
TPO-R
thrombopoietin-receptor
ULN
upper limit of normal
VEGF
vascular endothelial growth factor
WBC
white blood cell
WHODD
World Health Organization Drug Dictionary
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1
INTRODUCTION
The purpose of this statistical analysis plan (SAP) amendment is to provide all information that 
is necessary to perform the required final statistical analysis of study TP0001. It also defines the 
summary tables, figures and listings (TFLs) to be included in the final clinical study report 
(CSR) according to the protocol.
This SAP is based upon, and assumes familiarity, with the following documents:

Final Protocol: 09 November 2015

Protocol Amendment 0.1 (Moldova): 18 November 2015

Protocol Amendment 0.2 (Germany): 12 January 2016

Protocol Amendment 0.3 (Poland): 23 May 2016

Protocol Amendment 0.4 (Romania): 11 August 2016

Protocol Amendment 1.0 (Global): 19 May 2016

Protocol Amendment 1.1 (Moldova): 23 May 2016

Protocol Amendment 1.3 (Poland): 09 June 2016

Protocol Amendment 2.0 (Global; not implemented): 21 October 2016

Protocol Amendment 3.0 (Global): 15 February 2017

Protocol Amendment 3.1 (Moldova): 08 March 2017

Protocol Amendment 3.3 (Poland): 07 March 2017

Protocol Amendment 3.4 (Romania): 10 March 2017

Protocol Amendment 3.5 (Georgia and Bulgaria): 23 August 2017

Protocol Amendment 3.6 (Moldova): 07 September 2017
Unless specified below, the study will be analyzed as described in the most recent version of the 
protocol (European Union Drug Regulating Authorities Clinical Trials [EudraCT]-Number: 
2015-003984-12).
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP amendment will be updated accordingly. In addition, if analysis definitions 
have to be modified or updated prior to database lock, a further SAP amendment will be 
required.
This SAP amendment 3 is due to various updates and clarifications of the analysis definitions 
suggested prior to and during the Data Evaluation Meeting 3 part 1 in December 2018.
If, after database lock, additional analyses are required to supplement the planned analyses 
described in this SAP, these changes will be described in the CSR together with the associated 
rationale. The content of this SAP is compatible with the International Council for 
Harmonisation (ICH)/Food and Drug Administration (FDA) E9 Guidance documents.
UCB is the Sponsor and PAREXEL is the Contract Research Organization (CRO) for this study.
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28 Jan 2019
Statistical Analysis Plan
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TP0001
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Page 13 of 128
2
PROTOCOL SUMMARY
2.1
Study objectives
2.1.1
Primary objective
The primary objective of this study is:

To evaluate the safety and tolerability of UCB7665 administered by subcutaneous (sc) 
infusion in subjects with primary immune thrombocytopenia (ITP)
2.1.2
Secondary objectives
The secondary objectives of this study are:

To assess the clinical efficacy of UCB7665 as measured by the change in platelet count

To assess the pharmacodynamic (PD) effect of UCB7665 as measured by the change in total 
immunoglobulin (Ig) G (IgG) concentration in serum
2.1.3
Exploratory objectives
The exploratory objectives of this study are:


To evaluate the clinical efficacy as measured by the change in ITP bleeding score

To evaluate the effect of UCB7665 on the concentrations of total protein, albumin, 
α-globulin and β-globulin, IgG subclasses, IgM, IgA, IgE and serum and plasma complement 
levels

To evaluate the emergence of anti-drug antibody (ADA) with respect to immunogenicity and 
pharmacokinetics (PK)/ pharmacodynamic (PD)

To evaluate the relationship between changes in platelet count and total IgG, IgG subclasses, 
ITP-specific autoantibodies

To assess the plasma concentrations of UCB7665 administered by sc infusion

To evaluate the genomic components of ITP to understand the molecular etiology, 
progression, and treatment of the disease, applicable only for subjects consenting to 
participate in the optional genomic analyses substudy

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28 Jan 2019
Statistical Analysis Plan
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TP0001
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2.2
Study variables
2.2.1
Safety variables
2.2.1.1
Primary safety variable
The primary safety variable is:

Occurrence of treatment-emergent adverse events (TEAEs)
2.2.1.2
Other safety variables
The other safety variables are:

Vital sign values and change from Baseline (systolic and diastolic blood pressure,
temperature, pulse rate respiratory rate and body weight) to each visit in the Dosing Period
and in the Observation Period up to Day 85 in Dose Arm 1 (4mg/kg once weekly [QWK]),
up to Day 71 in Dose Arm 2 (7mg/kg QWK), up to Day 64 in Dose Arm 3 (10mg/kg QWK)
and up to Day 57 in Dose Arms 4 (15mg/kg) and 5 (20mg/kg). Body weight is measured only
at Screening and at the corresponding EOS/EW visit as outlined in the protocol

12-lead electrocardiogram (ECG) parameters and change from Baseline to each dosing visit
in the Dosing Period and to the second and the last visit in the Observation Period as outlined
in the protocol

Laboratory values and change from Baseline (hematology including coagulation parameters,
clinical chemistry, and urinalysis) to each visit in the Dosing Period and in the Observation
Period up to the corresponding EOS/EW visit as outlined in the protocol

Values and change from Baseline in concentrations of total protein, albumin, α-globulin, and
β-globulin to each visit in the Dosing Period and in the Observation Period up to the
corresponding EOS/EW visit as outlined in the protocol

TEAEs leading to withdrawal of UCB7665

Change from Baseline in serum biomarkers
 to each visit in the Dosing Period and up to the last visit prior to the 
corresponding EOS visit as outlined in the protocol
2.2.2
Efficacy variables
The efficacy variables are as follows where all variables relating to platelets refer to those 
measured by ACM Global Central Laboratory:

Response during the study: platelet count ≥30x109/L and at least 2-fold increase from the
Baseline count

Complete Response during the study: platelet count ≥100x109/L

Platelet count ≥50x109/L during the study

Response by visit

Complete Response by visit

Platelet count ≥50x109/L by visit
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28 Jan 2019
Statistical Analysis Plan
UCB7665
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
The maximum value and maximum increase from Baseline in platelet count during the study

Value and change from Baseline in platelet count over time

Baseline-corrected area under the effect curve (AUEC) for platelet count calculated from 
Baseline to the end of study visit (Day 85 in the Observation Period in Dose Arm 1, Day 71 
in the Observation Period in Dose Arm 2, Day 64 in the Observation Period in Dose Arm 3
and Day 57 in Observation Period in Dose Arms 4 and 5)

Time to Response: time from starting treatment to achievement of Response

Time to Complete Response: time from starting treatment to achievement of Complete 
Response

Time to achieving platelet count ≥50x109/L

Duration of Response: measured from achievement of Response to loss of Response (loss of 
Response defined as platelet count <30x109/L or less than 2-fold increase of Baseline platelet 
count)

Duration of Complete Response: measured from achievement of Complete Response to loss 
of Complete Response (loss of Complete Response defined as platelet count <100x109/L)

Duration of platelet count ≥50x109/L: measured from achievement of platelet count 
≥50x109/L to reduction of platelet count <50x109/L

Clinical Response: confirmation of platelet count ≥30x109/L and at least 2-fold increase from 
the Baseline value and absence of bleeding

Time to Clinical Response: time from starting treatment to achievement of Clinical Response

Duration of Clinical Response: measured from achievement of Clinical Response to loss of 
Clinical Response (loss of Clinical Response defined as platelet count <30x109/L or less than 
2-fold increase from Baseline platelet count or presence of bleeding)

Complete Clinical Response: confirmation of platelet count ≥100x109/L and absence of 
bleeding

Time to Complete Clinical Response: time from starting treatment to achievement of 
Complete Clinical Response

Duration of Complete Clinical Response: measured from achievement of Complete Clinical 
Response to loss of Complete Clinical Response (loss of Complete Clinical Response defined 
as platelet count <100x109/L or presence of bleeding)

No Clinical Response: confirmation of platelet count <30x109/L and less than 2-fold increase 
from Baseline or presence of bleeding

Assessment of ITP bleeding score over time at Baseline and at each dosing visit in the 
Dosing Period and to Day 36, Day 50, Day 64 and Day 85 in the Observation Period in Dose 
Arm 1, to Day 22, Day 36, Day 50 and Day 71 in the Observation Period in Dose Arm 2, to 
Day 15, Day 29, Day 43 and Day 64 in the Observation Period in Dose Arm 3 and to Day 8, 
Day 22, Day 36 and Day 57 in the Observation Period in Dose Arms 4 and 5
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 16 of 128

Value and change from Baseline in Neurological Fatigue Index for Multiple Sclerosis 
(NFI-MS) summary score to Day 36, Day 50, Day 64 and Day 85 in the Observation Period 
in Dose Arm 1, to Day 22, Day 36, Day 50 and Day 71 in the Observation Period in Dose 
Arm 2, to Day 15, Day 29, Day 43 and Day 64 in the Observation Period in Dose Arm 3 and 
to Day 8, Day 22, Day 36 and Day 57 in the Observation Period in Dose Arm 4 and 5
2.2.3
Pharmacokinetic and pharmacodynamic variables
2.2.3.1
Pharmacokinetic variable
The PK variable is:

Plasma concentration of UCB7665 over time, at each visit during the Dosing Period and 3 
and 7 days following the last dose of UCB7665 in each dose arm

Additional blood samples for the optional PK/PD substudy (early blood sampling) will be 
drawn at Visit 2 (predose and 4 hours after end of infusion on Day 1), Visit 2a (24 and 36 
[optional] hours after the start of Day 1 UCB7665 infusion) and Visit 2b (48 hours after the 
start of Day 1 UCB7665 infusion).
2.2.3.2
Pharmacodynamic variables
The PD variables are:

Minimum value and maximum decrease from Baseline in total IgG concentration (absolute 
and percentage) measured by ACM Global Central Laboratory

Value and change from Baseline (absolute and percentage) in total IgG concentrations
(measured by ACM Global Central Laboratory) to each visit in the Dosing Period and in the 
Observation Period up to Day 85 in Dose Arm 1, up to Day 71 in Dose Arm 2, up to Day 64 
in Dose Arm 3 and up to Day 57 in Dose Arms 4 and 5

ITP-specific autoantibodies in serum
over time, 
measured at Day 1, Day 36 and Day 85 in Dose Arm 1, at Day 1, Day 22 and Day 71 in Dose 
Arm 2, at Day 1, Day 15, and Day 64 in Dose Arm 3 and at Day 1, Day 8 and Day 57 in 
Dose Arms 4 and 5

Change from Baseline in IgG subclass concentrations (measured by ACM Global Central 
Laboratory) to each visit in the Dosing Period and in the Observation Period up to Day 85 in 
Dose Arm 1 and up to Day 71 in Dose Arm 2, up to Day 64 in Dose Arm 3 and up to Day 57 
in Dose Arms 4 and 5
2.2.4
Other immunological variables
Other immunological variables are:

Change from Baseline in serum immunoglobulin concentrations (total IgA, IgE, and IgM) to 
the last visit in the Dosing Period and to Day 36 and Day 71 in the Observation Period in 
Dose Arm 1, to Day 22 and Day 57 in the Observation Period in Dose Arm 2, to Day 15 and
Day 50 in the Observation Period in Dose Arm 3 and to Day 8 and Day 43 in the Observation 
Period in Dose Arms 4 and 5

Change from Baseline in serum (C3 and C4) and plasma (C3a and C5a) complement levels 
to Day 15 (Dosing Period) and to Day 32 and Day 57 in the Observation Period in Dose 
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 17 of 128
Arm 1, to Day 15 (Dosing Period) and to Day 18 and Day 43 in the Observation Period in 
Dose Arm 2, to Day 11 and Day 36 in Observation Period in Dose Arm 3 and to Day 4 and 
Day 29 in Observation Period in Dose Arms 4 and 5

Change from Baseline in exploratory biomarkers relating to mechanism of action, disease 
activity, treatment response, and clinical outcome

Value and change from Baseline in ADA relative mass units (RMU) to each visit in the 
Dosing Period and to Day 32, Day 36, Day 43, Day 57, Day 71 and Day 85 in the 
Observation Period in Dose Arm 1, and to Day 18, Day 22, Day 29, Day 43, Day 57 and 
Day 71 in the Observation Period in Dose Arm 2, to Day 11, Day 15, Day 22, Day 36, Day 
50 and Day 64 in Dose Arm 3 and to Day 4, Day 8, Day 15, Day 29, Day 43 and Day 57 in 
Dose Arms 4 and 5

Anti-drug antibody screening status (positive/negative) at each of the visits described above. 
For ADA screening positive results the confirmatory ADA result will be reported as either 
confirmed positive (CP) or not confirmed positive (NCP).

Change from Baseline in cytokines over time. Cytokines will be measured at all visits in all
dose arms for subjects who experience infusion reactions only. Further description of the 
cytokines variables can be found in Appendix 13.4. Additional exploratory biomarkers may 
be investigated if needed using the samples already available.

Change from Baseline in serum B cell activating factor (BAFF) levels to each dosing visit in 
the Dosing Period and to Day 43 and Day 71 in the Observation Period in Dose Arm 1, to 
Day 29 and Day 57 in the Observation Period in Dose Arm 2, to Day 22 and Day 50 in the 
Observation Period in Dose Arm 3 and to Day 15 and Day 43 in the Observation Period in 
Dose Arms 4 and 5

Change from Baseline in B- and T-lymphocyte concentrations to each visit in the Dosing 
Period and in the Observation Period up to Day 85 in Dose Arm 1, up to Day 71 in Dose 
Arm 2, up to Day 64 in Dose Arm 3 and up to Day 57 in Dose Arms 4 and 5
2.3
Study design and conduct
This is a Phase 2, multicenter, open-label, multiple-dose, multiple-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 in subjects with primary persistent or chronic ITP. 
The 5 dose arms will be as follows:

Dose Arm 1 (15 subjects): UCB7665 4mg/kg sc (5 doses at an interval of 1 week)

Dose Arm 2 (15 subjects): UCB7665 7mg/kg sc (3 doses at an interval of 1 week)

Dose Arm 3 (6 to 12 subjects): UCB7665 10mg/kg sc (2 doses at intervals of 1 week)

Dose Arm 4 (6 to 12 subjects): UCB7665 15mg/kg sc (1 dose)

Dose Arm 5 (6 to 12 subjects): UCB7665 20mg/kg sc (1 dose)
The maximum duration of the study per subject is approximately 16 weeks, consisting of a 
Screening Period (1 to 28 days), a Dosing Period of 1 to 4 weeks, and an Observation Period of 8 
weeks.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 18 of 128
A data monitoring committee (DMC) will monitor emergent safety data during the study. The 
first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in Dose Arm 1 will 
not be randomized. While recruitment is still ongoing safety data for the first 3 subjects up to 7 
days after the final dose of the third subject in Dose Arm 1 will be reviewed by the DMC. 
During a second DMC meeting, all available safety data up to the cut off date defined as 7 days 
after the final dose of the sixth subject in Dose Arm 1 will be reviewed. During these reviews 
recruitment in the dose arm will not be stopped. Following this review, the DMC will make a 
decision on whether to open Dose Arm 2 for enrollment. Once the DMC has advocated the 
initiation of Dose Arm 2, the subsequent subjects will be randomly assigned in 1:1 ratio to either 
Dose Arm 1 or Dose Arm 2 using an interactive voice/web response system (IXRS). Once 15 
subjects are enrolled in Dose Arm 1, the remaining subjects will enrolled in Dose Arm 2.
After the safety data review of at least 6 subjects in Dose Arm 2 is done, the DMC will make a 
recommendation on whether to open Dose Arm 3 for enrollment. Once the DMC has advocated 
the initiation of Dose Arm 3 and the enrollment of 15 subjects in Dose Arm 2 has been 
completed, the subsequent subjects will be assigned to Dose Arm 3 only. After every third 
subject has been enrolled, the DMC will review all available safety data up to cut off date 
defined as 7 days after the dosing. Depending on the emerging safety data of 6 subjects in Dose 
Arm 3, the DMC will recommend whether to open Dose Arm 4 for enrollment or to include 
additional subjects in Dose Arm 3. A maximum of 12 subjects may be enrolled in Dose Arm 3.
Once the DMC has advocated the initiation of Dose Arm 4, the enrollment of Dose Arm 3 will 
be closed and all subsequent subjects will be assigned to Dose Arm 4. After every third subject is 
enrolled, the DMC will review all available safety data up to the cutoff date defined as 7 days 
after the dosing. Depending on the emerging safety data of 6 subjects in Dose Arm 4, the DMC 
will recommend to include additional subjects in Dose Arm 4 or not. A maximum of 12 subjects 
may be enrolled in Dose Arm 4. The DMC will recommend to open Dose Arm 5 for enrollment 
in a subsequent meeting, if applicable. 
Once the DMC has advocated the initiation of Dose Arm 5, the enrollment of Dose Arm 4 will 
be closed and all subsequent subjects will be assigned to Dose Arm 5. After every third subject is 
enrolled, the DMC will review all available safety data up to the cutoff date defined as 7 days 
after the dosing. Depending on the emerging safety data of 6 subjects in Dose Arm 5, the DMC 
will recommend to include additional subjects in Dose Arm 5. A maximum of 12 subjects may 
be enrolled in Dose Arm 5.
At least 11 interim analyses will be performed. Based on the interim analyses the DMC will 
assess the safety of UCB7665, determine whether to initiate subsequent dose arms and may 
decide to adapt the dose regimen. The analyses and TFLs required for the interim analyses are 
described in a separate interim SAP.
During this study, subjects will also have the option of providing additional informed consent for 
exploratory deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) analyses. Participation in 
this additional portion of the study is optional and does not preclude subject’s eligibility for 
participation in the main study. The additional genomic samples must not be collected if the 
subject has not consented to participate in this exploratory genomic substudy. Any results from 
this analysis will be reported separately and will not form a part of the main CSR. Thus, these 
analyses are not described further in this SAP.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 19 of 128
During this study, subjects from Bulgaria, Georgia and Moldova who are enrolled in Dose Arm 
3, 4 or 5, will also have the option of providing additional informed consent for a PK/PD 
substudy (early blood sampling) at selected study sites. Participation in this additional portion of 
the study is optional and does not preclude subject’s eligibility for participation in the main 
study. The additional PK/PD blood samples must not be collected if the subject has not 
consented to participate in this exploratory substudy.
2.4
Determination of sample size
The sample size of 15 subjects in Dose Arms 1 and 2, is mainly based on the efficacy objective 
of the study. In addition, the inclusion of 15 subjects in Dose Arms 1 and 2 will ensure that 
sufficient data are available to form conclusions about the safety of administering UCB7665.
Based on the safety data from Dose Arms 1 and 2, the sample size of 6 to 12 subjects in Dose 
Arms 3, 4 and 5 were judged to be sufficient in order to explore subjects’ safety and IgG 
reductions under different dose regimens and is not based on a formal sample size calculation
For Dose Arms 1 and 2 an approximate sample size calculation for the efficacy variable 
“maximum increase from Baseline in platelet count” shows that 15 subjects would be sufficient 
to show a change from Baseline with 1-sided testing at 5% and power of 80%. The anticipated 
change is based on an assumed Baseline average of 25x109/L and a clinically meaningful 
maximum value of 100x109/L. The calculation made use of platelet count data presented in a 
publication by Robak (Robak et al, 2009), but it is approximate as maximum changes from 
Baseline for individual subjects were not available, necessitating the use of the maximum 
average platelet count instead. The standard deviation (SD) is taken from visual inspection.
With 15 subjects, the responder endpoints will confirm a true 50% response rate, in excess of the 
maximum 15% anticipated with no treatment benefit, with power in excess of 80%.
3
DATA ANALYSIS CONSIDERATIONS
3.1
General presentation of summaries and analyses
Statistical evaluation will be performed by PAREXEL. The datasets will follow the UCB 
analysis data model (ADaM) specifications.
All analyses will be performed using SAS version 9.3 or higher (SAS Institute, Cary, North 
Carolina, United States of America). Continuous variables will be summarized by visit (where 
applicable) including number of subjects (n), arithmetic mean, SD, median, minimum and
maximum. Categorical variables will be summarized by visit (where applicable) with frequency 
counts and percentages with 95% confidence intervals (CI) where stated. Geometric coefficient 
of variation (geoCV), geometric mean (geoMean) and 95% CI for the geoMean will also be 
presented in the descriptive statistics for the PK concentration data. 
When reporting relative frequencies or other percentage values, the following rules apply:

For values where all subjects fulfill certain criteria, the percentage value will be displayed as 
100

For values where the absolute frequency is zero, there will be no percentage displayed at all

All other percentage displays will use 1 decimal place
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 20 of 128
Percentages displayed based on continuous data (eg, percentage changes from baseline) will be 
displayed to 1 decimal place.
When reporting descriptive statistics, the following rules will apply in general:

n will be an integer

Mean (arithmetic and geometric), SD and median will use 1 decimal place more than the 
original data

Minimum and maximum will be reported using the same number of decimal places as the 
original value

If no subjects have data at a given timepoint, for example, then only n=0 will be presented. If 
n<3, present the n, minimum and maximum only. If n=3, present the n, mean, median, 
minimum and maximum only. The other descriptive statistics will be left blank.
When reporting descriptive statistics for PK data, the following rules will apply with regard to 
rounding and precision:

Individual values for PK concentration data will be reported to the same level of precision as 
received from the bioanalytical laboratory

Descriptive statistics for PK concentration data will be reported to the same level of precision 
as the individual data for the minimum and maximum, and to 1 additional significant figure 
for the mean (arithmetic and geometric), median, SD and 95% CI for the geoMean

Geometric CV will be reported as a percentage to 1 decimal place
All statistical tests will be carried out 1-tailed at the 5% level of significance unless otherwise 
stated. P-values will be presented to 4 decimal places; p-values less than 0.0001 will be 
presented as “<0.0001” and p-values greater than 0.9999 will be presented as “>0.9999”. All 
statistical output will be presented in statistical appendices where appropriate.
Analyses will be performed by dose arm for all efficacy, immunological, PK, PD and safety data, 
with the exception of adverse event (AE) data which will be presented by dose arm and overall
(Section 13.6). 
In the event that the number of planned infusions in the dose arms are modified following review 
by the DMC, the data will be summarized based on the actual dose arms completing the study. 
For example, if the 5x4 mg/kg QWK dose arm is modified such that some subjects receive only 
4 infusions, then the data will be summarized separately for this new dose regimen.
In the TFLs the dose arms will be displayed as follows where applicable:

UCB7665 5x4mg/kg

UCB7665 3x7mg/kg

UCB7665 2x10mg/kg

UCB7665 1x15mg/kg

UCB7665 1x20mg/kg
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 21 of 128
If additional dose arms are initiated during the study these will be displayed similarly. For 
example, if the 5x4 mg/kg QWK dose arm is modified such that some subjects receive only 4 
infusions this dose arm will be displayed as UCB7665 4x4mg/kg QWK in the TFLs.
Data listings containing all documented data and all derived data will be generated.
3.2
General study level definitions
3.2.1
Analysis timepoints
3.2.1.1
Relative day
Relative day for an event will be derived with the date of the first infusion of UCB7665 as 
reference.
Relative days for an event of measurement occurring before the date of first infusion are 
calculated as follows:
Relative Day = [(Event Date – Date of First Infusion)]
The relative day for an event or measurement occurring on or after the reference date to the date 
of the last infusion is calculated as follows:
Relative Day = [(Event Date - Date of First Infusion) + 1]
For events or measurements occurring after the date of the last infusion, relative day will be 
prefixed with ‘+’ in the data listings and will be calculated as follows:
Relative Day = + [(Event Date – Date of Last Infusion)]
There is no relative Day 0. Relative day is not calculated for partial dates in cases where relative 
day is shown in a subject data listing. In such cases, relative day should be presented as ‘-‘ in the 
subject data listings.
3.2.1.2
Study periods
For each subject the duration of the study is approximately 16 weeks.

Screening Period: 1 to 28 days

Dosing Period: 1 to 4 weeks; during the Dosing Period subjects will receive weekly doses of 
UCB7665 (5 doses of 4mg/kg [QWK] in Dose Arm 1, 3 doses of 7mg/kg [QWK] in Dose
Arm 2, 2 doses of 10mg/kg [QWK] in Dose Arm 3, 1 dose of 15mg/kg in Dose Arm 4 and 1 
dose of 20mg/kg in Dose Arm 5). The dose regimen may be adapted following review by the 
DMC

Observation Period: 8 weeks; a visit will be scheduled 3 days after the final dose (or only 
dose administration for Dose Arms 4 and 5) and weekly thereafter to collect safety and 
efficacy data
The end of the study is defined as the date of the last visit of the last subject in the study.
3.3
Definition of Baseline values
Baseline will be the last available predose value prior to the first infusion of UCB7665, or if
missing, the latest non missing value prior to Baseline (screening value or unscheduled visit 
value). 
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 22 of 128
Measurement-specific Baseline timepoints (based on the scheduled or unscheduled 
measurements) are presented in Table 3‒1.
Table 3‒1:
Definition of Baseline
Measurement
Definition of Baseline
Safety data:

Clinical chemistry (including proteins)

Hematology (including platelets measured 
locally)

Coagulation

Urinalysis

Vital signs

12-lead ECG

Serum safety biomarkers 

Predose Day 1 or if missing the latest non
missing value prior to Day 1
Efficacy variables:

Platelets (measured by ACM Global 
Central Laboratory)

ITP bleeding scale

NFI-MS

Platelets: Predose Day 1 or if missing the 
latest non missing value prior to Day 1

ITP bleeding scale: Predose Day 1 or if 
missing the latest non missing value prior 
to Day 1

NFI-MS: Predose Day 1
Pharmacodynamic variables:

Total IgG

IgG subclasses


ITP-specific autoantibodies in serum 

Total IgG: Predose Day 1 or if missing the 
latest non missing value prior to Day 1

IgG subclasses: Predose Day 1 or if 
missing the latest non missing value prior 
to Day 1

ITP-specific autoantibodies: Predose Day 1
Immunological variables:

Immunoglobulins (IgA, IgE and IgM)

B- and T-lymphocytes

Serum (C3 and C4) and plasma 
complement (C3a and C5a)

ADA

Serum BAFF

Cytokines, if applicable (as outlined in the 
protocol)

Predose Day 1 (except B- and T-
lymphocytes)

B- and T-lymphocytes: Predose Day 1 or if 
missing the latest non missing value prior 
to Day 1
ADA=anti-drug antibody; BAFF= B cell activating factor; ECG=electrocardiogram; Ig=immunoglobulin; 
ITP=primary immune thrombocytopenia; NFI-MS= Neurological Fatigue Index for Multiple Sclerosis;
If a measurement is repeated at Baseline and is obtained prior to receiving the first dose of 
UCB7665, then the last available measurement will be used as the Baseline value.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 23 of 128
For the platelet count performed at Screening (measured by ACM Global Central Laboratory 
only), 2 separate blood samples will be obtained on the same day. If the latest non missing value
prior to Baseline is to be used as Baseline (i.e., predose Day 1 is missing), the highest value for 
the platelet count obtained from the last 2 non missing measurements prior to Baseline will be 
used as the Baseline.
3.4
Protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct or on the primary efficacy, key safety, or PK/PD outcomes 
(if applicable) for an individual subject. The criteria for identifying such protocol deviations will 
be defined within the important protocol deviation specifications which is part of the data 
cleaning plan. Important protocol deviations will be reviewed as part of the ongoing data 
cleaning process and data evaluation. All important protocol deviations will be discussed and 
documented at the data evaluation meeting (DEM) together with any decisions regarding 
exclusion from analysis sets.
3.5
Analysis sets
3.5.1
Enrolled Set
The Enrolled Set (ES) will consist of all subjects who have given informed consent. This will 
include screening failures. Screening failures will be labeled as ‘not treated’ in any outputs based 
on the ES.
3.5.2
Safety Set
The Safety Set (SS) will consist of all subjects who have received at least 1 infusion (full or 
partial infusion) of UCB7665 and will be used for the analysis of safety data.
3.5.3
Full Analysis Set
The Full Analysis Set (FAS) will consist of all subjects who have received at least 1 infusion 
(full infusion) of UCB7665 and, in addition, have a Baseline and at least 1 post-Baseline 
measurement for platelet count (measured by ACM Global Central Laboratory).
The analysis of the PD (excluding total IgG and IgG subclasses), efficacy and immunologic 
variables will be performed on the FAS. Efficacy analyses will be repeated for the 
pharmacodynamics per protocol set (PD-PPS) where stated in the SAP.
Platelet data for subjects who have taken rescue medications (based on medical review and 
defined in Section 8.1.4) will only be utilized in the summary tables up to the start of these 
rescue medications.
3.5.4
Per Protocol Set
The Per Protocol Set (PPS) is a subset of the FAS, consisting of those subjects who had received 
all foreseen sc infusions, had a platelet count measurement (measured by ACM Global Central 
Laboratory) during the Observation Period, and no important protocol deviations that may 
potentially affect the platelet count as confirmed during a pre-analysis review of the data prior to 
database lock. Protocol deviations may not necessarily lead to total exclusion of a subject from 
the PPS but may lead to exclusion of specific data and/or timepoints from the analysis.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 24 of 128
Platelet data for subjects who have taken prohibited medications potentially affecting platelet 
counts such as IV corticosteroids, TPO-Rs, Oral corticosteroids, immunosuppressants (based on 
medical review) will only be utilised in the summary tables, up to the start date of these 
prohibited medications.
3.5.5
Pharmacokinetic Per Protocol Set
The Pharmacokinetic Per Protocol Set (PK-PPS) is a subset of the FAS, consisting of those 
subjects who had no important protocol deviations potentially affecting the plasma concentration 
of UCB7665, as confirmed during a pre-analysis review of the data prior to database lock.
3.5.6
Pharmacodynamic Per Protocol Set
The Pharmacodynamic Per Protocol Set (PD-PPS) is a subset of the FAS, consisting of those 
subjects who had no important protocol deviations potentially affecting the serum concentration 
of total IgG, as confirmed during a pre-analysis review of the data prior to database lock.
Protocol deviations may not necessarily lead to total exclusion of a subject from the PD-PPS but 
may lead to exclusion of specific data.
The PD-PPS will be used for the analysis of the total IgG and IgG subclasses.
3.6
Treatment assignment and treatment groups
Treatment (dose arm) assignment for the SS, FAS, PK-PPS, PD-PPS and the PPS will be 
according to the planned treatment regimen (reflecting the potential DMC decisions).
In the event that the number of planned infusions in the dose arms are modified following review 
by the DMC, the data will be summarized based on the actual dose arms completing the study. 
For example, if the weekly 5x4mg/kg QWK dose arm is modified such that some subjects 
receive only 4 infusions, then the data will be summarized separately for this new dose regimen.
Analyses will be performed by dose arm, unless otherwise stated. 
3.7
Center pooling strategy
The clinical study will be conducted in multiple centers in Europe and Australia. The data from 
different sites will be pooled for all analyses. There will be no analyses by site or country 
performed.
3.8
Coding dictionaries
Adverse events and medical history will be coded using the latest available version of the 
Medical Dictionary for Regulatory Activities (MedDRA®). 
Medications will be coded according to the World Health Organization Drug Dictionary 
(WHODD [September 2015]). Medical procedures will not be coded.
3.9
Changes to protocol-defined analyses
The protocol stated that changes from Baseline would be evaluated for the ITP-specific 
autoantibodies. However, as these data are semi-quantitative, changes from Baseline are not 
considered an appropriate way to present the results and would not provide any additional 
information. Thus, only absolute values over time will be reported. 
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 25 of 128
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
There will be no adjustment for covariates.
4.2
Handling of dropouts or missing data
In general, there will be no imputation of missing data unless otherwise stated below.
4.2.1
Efficacy data
There will be no imputation of missing platelet data (measured by ACM Global Central 
Laboratory) or missing data for the ITP bleeding score. Missing data for the calculation of the 
NFI-MS summary score will be handled as described in Section 13.2.
4.2.2
Safety laboratory data
Measurements below the limit of quantification (BLQ) will be imputed with half of the lower 
limit of quantification (LLOQ) for the purpose of calculating change from Baseline and for 
descriptive statistics. Measurements above the limit of quantification (ALQ), if applicable, will 
be imputed to the upper quantification limit.
These rules will be applied to all safety laboratory data including coagulation parameters, clinical 
chemistry and urinalysis. 
4.2.3
Pharmacodynamic data
Measurements BLQ are not anticipated in the PD data (total IgG [measured by ACM Global 
Central Laboratory] and IgG subclasses). In the event that any BLQ measurements are received,
these will be discussed at the DEM.
For the ITP-specific autoantibodies any measurements that are above the limit of detection 
(ALD) will be imputed with the value of the upper quantification limit for the calculation of 
summary statistics.
4.2.4
Immunological data
The rules for handling BLQ or ALQ measurements for all immunological data (including IgA, 
IgE, IgM, B- and T-lymphocytes, serum and plasma complement, serum biomarkers (including 
BAFF), ADA and cytokines) will be as described in Section 4.2.2.
For all immunological data, measurements that are BLQ will be imputed with LLOQ/2 for 
individual plots.
4.2.5
UCB7665 concentration data
Measurements that are BLQ will be imputed with LLOQ/2 for the purpose of calculating the 
geoMean and its 95% CI, the geoCV, the arithmetic mean, and SD for summaries and figures.
For the individual figures, any concentrations that are BLQ will be imputed with LLOQ/2, with 
the exception of predose BLQ measurements on Day 1, which will be imputed with zero for 
linear scale plots.
Additional rules for PK data summaries are provided in Section 9.1.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 26 of 128
4.2.6
Electrocardiogram data
For the ECG data, all calculations of changes from Baseline and descriptive statistics will be 
based on the mean of the triplicate assessments at each visit. In the event that there are not 3 
available measurements at a given visit, the mean will be calculated based on the number of 
measurements for which data is provided (variables analyzed will be those described in Section 
10.4.2).
4.2.7
Dates and times
Partial dates may be imputed for the following reasons:

Classification of AEs as treatment-emergent

Classification of medications as past, prior or concomitant
Imputed dates will not be shown in the listings; all dates will be displayed as reported in the 
database.
The following rules will be applied for partial start dates:

If only the month and year are specified and the month and year of first dosing is not the 
same as the month and year of the start date then use the 1st of the month, or the date of 
screening if this is later (if the latter imputation results in an end date that is earlier than the 
start date, then use the 1st of the month). If time is missing this will be imputed as 00:00 h;

If only the month and year are specified and the month and year of first dosing is the same as 
the month and year of the start date, then use the date of first dosing. If this results in an 
imputed start date that is after the specified end date, then use the 1st of the month, or the date 
of screening if this is later (if the latter imputation results in an end date that is earlier than 
the start date, then use the 1st of the month). If the imputed date is the date of first dosing then 
time will be imputed as the start time of the infusion (i.e., event will be regarded as 
treatment-emergent);

If only the year is specified, and the year of dosing is not the same as the year of the start date 
then use January 01 of the year of the start date. If time is missing this will be imputed as 
00:00 h;

If only the year is specified, and the year of dosing is the same as the year of the start date, 
then use the date of dosing. If this results in an imputed start date that is after the specified 
end date, then use January 01 of the year of start date, or the date of screening if this is later
(if the latter imputation results in an end date that is earlier than the start date, then use 
January 01). If the imputed date is the date of first dosing then time will be imputed as the 
start time of the infusion (i.e., event will be regarded as treatment-emergent);

If the start date is completely unknown, then use the date of first dosing. If this results in an 
imputed start date that is after the specified end date, then use January 01 of the year of the 
end date, or the date of screening if this is later (if the latter imputation results in an end date 
that is earlier than the start date, then use January 01). If the imputed date is the date of first 
dosing then time will be imputed as the start time of the infusion (i.e., event will be regarded 
as treatment-emergent).
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 27 of 128
Start and end time is not recorded for concomitant medications, thus no imputations for missing 
times will be performed. Any medication with a start date on the first dosing date, will be 
assumed to be concomitant.
The following rules will be applied for partial stop dates:

If only the month and year are specified, then use the last day of the month;

If only the year is specified, then use December 31 of the known year;

If the stop date is completely unknown, do not impute the stop date, except for ITP 
medications where end date is missing and ongoing is ticked as ‘no’, which will be imputed 
as “Past” medications.
Missing or partially missing date and/or times will be imputed as described in Table 4‒1 for the 
calculation of duration of each AE. Adverse event duration is computed and reported in day and 
time format: xx d hh:mm.
Table 4‒1:
Calculation rules for duration of adverse events
Data availability
Onset 
date/time
Outcome 
date/time
Calculation rules
Complete data
D1/T1
D2/T2
Duration = [(D2 – D1)*24 + (T2 – T1)]/24 d
End time missing
D1/T1
D2/--
End time is substituted by time 23:59h (=23.98 in 
decimal format)
Duration = <[(D2 – D1)*24 + (23.98 – T1)]/24 d
Start time missing
D1/--
D2/T2
Onset time is substituted by time 00:00h.
Duration = <[(D2 – D1)*24 + T2]/24 d
Start and end time 
missing
D1/--
D2/--
Duration = <D2 – D1 + 1
Start day and time 
missing
--/--
D2/T2
Duration = <[(D2 – D0)*24 + (T2 – T0)]/24 d
For a subject in the SS, D0 and T0 are the date and 
time of first administration of UCB7665 and for 
screen failures, D0 is the date of the screening visit 
and T0 = 00:00h
End day and time 
missing
D1/T1
--/--
For ongoing AE:
Duration = >Discharge day – D1 d
For resolved AE:
Duration = <Discharge day – D1 d
Where discharge refers to the date of the end of study 
visit or the date of discontinuation for subjects that 
were withdrawn.
For any AEs with known start date/time after the date 
of discontinuation, the date of last contact will be 
used as the discharge day.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 28 of 128
Table 4‒1:
Calculation rules for duration of adverse events
Data availability
Onset 
date/time
Outcome 
date/time
Calculation rules
Start and end date 
missing
--/--
--/--
For ongoing AE:
Duration = >Discharge day – D0 d
For resolved AE:
Duration = <Discharge day – D0 d
For a subject in the SS, D0 and T0 are the date and 
time of first administration of UCB7665 and for 
screen failures, D0 is the date of the screening visit 
and T0 = 00:00h.
Discharge refers to the date of the end of study visit 
or the date of discontinuation for subjects that were 
withdrawn.
For any AEs with known start date/time after the date 
of discontinuation, the date of last contact will be 
used as the discharge day.
4.3
Handling of repeated and unscheduled measurements
All repeated and unscheduled measurements will be presented in the listings, where applicable. 
The following general rules will apply to all repeated and unscheduled measurements:

For repeated and unscheduled measurements obtained prior to the first dose of UCB7665 the 
latest value (which may be scheduled or unscheduled) will be used in the calculation of 
descriptive statistics;

For repeated and unscheduled measurements obtained at the designated Baseline visit, the 
latest value (which may be scheduled or unscheduled) will be defined as the Baseline 
provided that this occurred prior to the first dose of UCB7665;

For repeated measurements obtained at any timepoint after the first dose of UCB7665, the 
first value of any repeated measurements will be used in the calculation of changes from 
Baseline and for the descriptive statistics. Unscheduled and repeated measurements will not 
be included in the descriptive statistics at timepoints after the first dose of UCB7665, 
however they may be included in any summaries for abnormal measurements.
The above rules are not applicable for the determination of the response variables for the platelet 
measurements; both scheduled and unscheduled measurements may be used in the calculation of 
response, time to response and duration of response (Section 8.1.1).
4.4
Interim analyses and data monitoring
For the sequential adaptive design in this study, at least 11 interim analyses will be performed.
Safety data from the interim analyses will be reviewed by the DMC to monitor the safety, to
adapt the dose regimen, and to decide when and if the UCB7665 7mg/kg weekly group (Dose 
Arm 2), UCB7665 10mg/kg weekly group (Dose Arm 3), UCB7665 15mg/kg group (Dose Arm 
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 29 of 128
4) and UCB7665 20mg/kg group (Dose Arm 5) should be opened, as well as whether the doses 
in any of the treatment groups should be modified.
A detailed description of the DMC composition, processes and responsibilities will be provided 
in a separate DMC Charter. The data required for review as well as the timing of each interim 
analysis is described in a separate interim SAP and includes all data specified in the DMC 
Charter, which is available at the time. For the interim analyses the data, subject to analysis, 
should be as clean as possible; however, the database will not be locked and a snapshot will be 
taken.
4.5
Multicenter studies
Individual center results will not be displayed.
4.6
Multiple comparisons/multiplicity
Not applicable.
4.7
Active-control studies intended to show equivalence
Not applicable.
4.8
Examination of subgroups
The following subgroups will be defined within each dose arm:

Concomitant corticosteroid medication: Yes/No
Concomitant medication is defined in Section 6.4.4. The list of applicable Anatomical 
Therapeutic Chemical (ATC) codes to be utilized as corticosteroids is provided in
Section 13.1.

Responder at the end of past ITP therapy: No/Yes/Unknown
Responder categories will be defined utilizing the value (either Yes or No) for the last 
reported ITP therapy for each patient. If this value is unknown, the second-last reported ITP 
therapy value will be used, then the third-last, and so on, until a known response is provided. 
The Unknown responder category will only be considered in cases where the investigator has 
never reported a category (Yes or No) for any of the past ITP therapies. For the ‘Response’ 
definition, the CRF entries will be utilized.
The past ITP therapy is defined as procedure history related to ITP or past medication related 
to ITP, where past medication is defined in Section 6.4.1. For ‘related to ITP’ CRF entries 
will be utilized.
The corticosteroid medication given more than 3 months prior to screening was routinely not 
recorded and cannot be considered. Thus, some patients with an unknown response might 
have had a known response.

Past intravenous immunoglobulin (IVIg) medication: Yes/No
Past medication is defined in Section 6.4.1. The ATC Therapeutic Subgroup code (Level 2) 
‘IMMUNE SERA AND IMMUNOGLOBULINS’ will be utilized.

Number of past ITP therapies: ≤2/>2
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28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 30 of 128
The past ITP therapy is defined as procedure history related to ITP or past medication related 
to ITP, where past medication is defined in Section 6.4.1. For ‘related to ITP’ CRF entries 
will be utilized.
The corticosteroid medication given more than 3 months prior to screening was routinely not 
recorded and cannot be considered. Thus, some patients might have had 1 more past ITP 
therapy than utilized for subgroup determination.
The descriptive summaries for platelets and total IgG will be presented for the subgroups above. 
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
The number of subjects who were enrolled, dosed, subjects included in each analysis set, and 
subjects who completed or prematurely discontinued the study, as well as the reason for 
discontinuation, will be presented by dose arm and overall. Screen failure reasons will be 
summarized, based on the ES.
In addition, the following listings will be presented by dose arm:

Subject disposition (ES)

Study discontinuation (SS)

Visit dates (SS)

Subject analysis sets (ES)
The listing of subject disposition will include the date of informed consent, date of genomic 
consent (if applicable), date of randomization (if applicable), date and time of first and last dose 
of UCB7665 (if applicable), date of premature termination and primary reason (if applicable) and 
date of final contact. 
The listing of study discontinuation will include the reason for discontinuation and the number of 
days on UCB7665.
The number of days on UCB7665 will be calculated as follows:
Number of days on UCB7665= [(Date of Last Dose Received) – (Date of First Dose Received)] 
+ 1
5.2
Protocol deviations
Important protocol deviations will be identified and classified by the deviation types identified in 
the important protocol deviations document. A listing of all important protocol deviations 
identified at the DEM will be presented for all subjects in the SS, and will include the deviation 
type and description. The number and percentage of subjects in the SS with important protocol 
deviations will be summarized by dose arm and overall. The denominator for percentages will be 
the number of subjects in the SS. 
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28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 31 of 128
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
6.1
Demographics
A by-subject listing of Baseline demographics will be presented by dose arm for the ES. This 
will include the year of birth (if available), age (in years), sex, race, ethnicity, height (in cm), 
weight (in kg) and body mass index (BMI). The age will be directly entered into the study 
database and will not be re-calculated for the statistical analysis.
BMI in kg/m2 is calculated based on the height (in m) and the weight (in kg) using the following 
formula:
BMI (kg/m2) = weight (kg)/[height (m)]2
BMI will be reported to 1 decimal place.
All Baseline demographic characteristics (with the exception of year of birth) will be 
summarized by dose arm and overall for the SS. Number and percentage of patients with a BMI 
equal or higher than 30 will also be summarized by dose arm.
The summary of age will include descriptive statistics and categorical summaries, the latter 
based on requirements for EudraCT and clinicaltrials.gov reporting. 
For the EudraCT reporting, the categories will include:

18 to <65 years

65 to <85 years

≥85 years
For the clinicaltrials.gov reporting, the categories will include:

≤18 years

19 to <65 years

≥65 years
Childbearing potential will be listed for the SS. 
6.2
Other Baseline characteristics
Baseline disease characteristics will be listed and summarized by dose arm for the SS including 
the following:

Duration of disease

Karnofsky Performance Scale Index

ITP bleeding scale (skin, visible mucosae and organs, with gradation of severity [SMOG])

ITP-specific autoantibodies 
expressed in terms of optical 
density (OD) for MAIPA analysis and pre-chloroquine minus post chloroquine treated scores 
for PIFT
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 32 of 128

Immunological variables (IgG [including total IgG and IgG subclasses measured by ACM 
Global Central Laboratory], IgM, IgA, IgE and lymphocytes [B and T])

Serum (C3 and C4) and plasma complement levels (C3a and C5a)

Platelet count (measured by ACM Global Central Laboratory)

Number of prior ITP medications received

Number of prior ITP medications received categorized

Prior ITP medications received by preferred term

Medical history of splenectomy (MedDRA v20.2, Preferred Term=”Splenectomy”)
The duration of disease will be calculated as follows, where the date of diagnosis will be 
obtained from the ITP history page of the case report form (CRF):
Duration (years) = (Date of Screening – Date of Diagnosis)
If the date of diagnosis is missing, the duration of disease will not be calculated. In the case of 
the start day being missing, the day will be imputed with the 1st of the month in the calculation of 
the disease duration. In the case of the start day and month being missing, the date will be 
imputed with 01 January in the calculation of the disease duration.
The disease duration will be presented in years to 1 decimal place in the listings.
The Karnofsky Performance Scale index is a semi-quantitative score ranging from 0 to 100% in 
intervals of 10, where 0% is death and 100% is normal (no complaints, no evidence of disease). 
Summary statistics for the Karnofsky Performance Scale will include n, median, minimum and 
maximum only.
The ITP bleeding scale will be summarized (n, median, minimum and maximum) by dose arm
for each domain (SMOG).
6.3
Medical history and concomitant diseases
Medical history will be summarized for the SS by dose arm and for all subjects by MedDRA 
system organ class (SOC), high level term (HLT) and preferred term (PT). The listing will also
include the reported condition and the start and end date (or ongoing, if applicable). Procedure 
history and history of thrombocytopenia will be listed separately by dose arm for the procedure 
reported term based on the SS.
Concomitant medical procedures performed during the study will be listed for the SS.
6.4
Past, prior, baseline and concomitant medications
Past, prior, baseline and concomitant medications will be summarized for the SS by dose arm
and for all subjects by WHODD Anatomical Main Group [Level 1], Therapeutic Subgroup 
[Level 2] and PT.
All medications will be listed and will include coding information, reported term, dose per intake 
and unit, frequency, formulation, route of administration, indication, category (past/prior and 
concomitant/concomitant) and start and end date (or ongoing, if applicable).
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 33 of 128
6.4.1
Past medication definition
Past medications will include any medications that started and stopped prior to the first 
administration of UCB7665.
6.4.2
Prior medication definition
Prior medications will include any medications that started prior to the first administration of 
UCB7665. This includes medications that started and stopped prior to dosing (past medications) 
as well as those that started prior to dosing and continued after (classified as prior and 
concomitant medications).
6.4.3
Baseline medication definition
Baseline medications will include any medications that started prior to dosing and continued 
after (classified as prior and concomitant medications).
6.4.4
Concomitant medication definition
Concomitant medications will include any medication that has been taken at least once (after the 
first administration of UCB7665) during the Dosing Period and/or the Observation Period.
This includes medications that started prior to the dosing and continued after (classified as prior 
and concomitant medications) as well as any medication that started after the first administration 
of UCB7665 (classified as concomitant).
Any medications with missing dates and/or times will be handled as described in Section 4.2.7 in 
order to classify them as prior and/or concomitant.
7
MEASUREMENTS OF TREATMENT COMPLIANCE
The study medication will be administered and monitored by the investigator or designee. The 
measured plasma concentrations will provide information regarding compliance. Any dosing 
deviations (eg, incomplete infusion volume administered, infusion discontinued) will be 
discussed at the DEM and any actions taken regarding the analyses will be documented 
accordingly and discussed in the CSR.
There will be no specific analysis of compliance. Exposure to UCB7665 will be presented as 
described in Section 10.1.
8
EFFICACY ANALYSES
All analyses of the efficacy variables will be performed on the FAS. Additional outputs may be 
repeated for the PPS where indicated. Treatment (dose arm) assignment for efficacy analysis will 
be according to the actual treatment regimen.
8.1
Platelets
All efficacy analyses are based on platelet count measured by ACM Global Central Laboratory. 
Measurements of platelet count obtained by the local laboratory will be listed and summarized as 
part of the safety laboratory data. These are not included in the analyses described in the sections 
below. All tabulations and mean figures will be presented for both the FAS and the PPS unless 
otherwise stated. Median figures and individual figures will be presented for the FAS only. In 
case rescue medications are taken, only the platelet data up to the start date of rescue medication
will be utilized for the summary tables (refer to Section 8.1.4). In case prohibited medications 
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 34 of 128
affecting platelets are taken, only the platelet data up to the start date of prohibited medication 
will be utilized for the summary tables for the PPS (refer to Section 3.4). Listings will contain all 
the data but a footnote will be included indicating the patients for which some data has been 
excluded from the summary tables. In case of partial dates, the imputation rules for partial dates 
described in Section 4.2.7 will be applied.
8.1.1
Definition of variables
The main efficacy variable is defined as the following:

Maximum Increase from Baseline: the Maximum Increase from Baseline (Day 1, predose) is 
defined as the highest positive change from Baseline during the study. In the event that the 
platelet count was to decrease during the study the Maximum Increase from Baseline may be 
negative and would correspond to the smallest decrease from the Baseline value
The following additional variables will be defined for the platelet count, the calculation rules for 
which are provided in the section immediately below:

Response: a platelet count ≥30x109/L and at least 2-fold increase from the Baseline value, by 
visit, and at any timepoint during the study

Time to Response: the first time that a given response is achieved during the study. Thus, in 
the event that the platelet count was to increase above the threshold level, decrease below the 
threshold level, and subsequently increase again the time to response would be to the first 
time the definition of response was achieved. The time to response will be calculated in days 
and presented to 1 decimal place in the listings.
Time to response (days) = Date/time of first response – Date/time of first dose of UCB7665

‘No’ or ‘Loss of’ Response: a platelet count <30x109/L OR >=30x109/L WITHOUT at least 
a 2-fold increase from the Baseline value, by visit

Duration of Response (including Complete Response, Response and Platelet Count 
≥50x109/L): the duration of the first time the response was achieved to first loss of response. 
The duration of response will be calculated in days and presented to 1 decimal place in the 
listings.
Duration of response (days) = Date/time of loss of first response – Date/time of first 
response, where “loss of first response” is defined as platelet count<30x109/L OR (platelet 
count ≥30x109/L WITHOUT at least a 2-fold increase from the Baseline value)
If the platelet value meets the criterion for a specific response for a second time (following a 
loss of initial response), the second response period will be added to the overall duration of 
response. This rule will be applied for any subsequent ‘response periods’. For subject in 
whom the response is maintained until the end of the study the duration of response will be 
calculated using the date of the end of study visit as the ‘end of response date’. Any such 
cases will be flagged in the data listings

Complete Response: a platelet count ≥100x109/L, by visit, and at any timepoint during the 
study

‘No’ or ‘Loss of’ Complete Response: a platelet count <100x109/L, by visit.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
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Page 35 of 128

Time to Complete Response: the time from starting treatment (Day 1) to achievement of 
Complete Response

Platelet Count ≥50x109/L, by visit, and at any timepoint during the study

‘No’ or ‘Loss of’ Platelet Count ≥50x109/L: a platelet count <50x109/L, by visit.

Time to Platelet Count ≥50x109/L: the time to Platelet Count ≥50x109/L is defined as the 
time from starting treatment (Day 1) to achievement of Platelet Count ≥50x109/L

Maximum: the maximum value for platelet count over all visits in the study

Value and change from Baseline in platelet count over time

Baseline-corrected AUEC for platelet count calculated from Baseline to the end of study visit 
for each of the defined dose arms.
For all the above response variables the following rules will apply:

Both scheduled and unscheduled measurements may be included in the calculation of a 
response, time to response or duration of response

The Baseline-corrected AUEC will be calculated according to the following rules:

The AUEC will be calculated according to the linear trapezoidal rule using protocol 
scheduled visits

Unscheduled visits will not be included in the calculation

No imputation of any missing data will be performed

To account for differences in the timing of Baseline samples for each subject the Baseline 
measurement will be considered as time zero in the calculation

The units of the AUEC will be 109/L*day

The measurements at Baseline and at the last visit must be available

A minimum of 10 out of 14 measurements must be available for the calculation in Dose 
Arm 1; a minimum of 9 out of 12 measurements must be available for the calculation in 
Dose Arm 2; a minimum of 8 out of 11 must be available for the calculation in Dose Arm
3; a minimum of 7 out of 9 must be available for the calculation in Dose Arms 4 and 5. 
These include the Baseline and measurement at the last visit

The AUEC will not be calculated in the case of early withdrawal from the study
8.1.2
Presentation of results
The individual platelet measurements will be listed by dose arm and visit including changes from 
Baseline (Day 1, pre-dose). Descriptive summaries (including n, arithmetic mean, median, SD, 
minimum and maximum) will be presented by dose arm and scheduled visit for both absolute 
values and changes from Baseline based on the FAS only. Summary tabulations by dose arm will 
be repeated for the subgroups defined in Section 4.8 (based on the FAS only too).
In addition, a separate listing and summary will be presented (by visit, where applicable)
including the following:
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 36 of 128

*Response by visit and over all visits

Time to Response

Duration of Response

*Complete Response by visit and over all visits

Time to Complete Response

Duration of Complete Response

*Platelet Count ≥50x109/L by visit and over all visits

Time to Platelet Count ≥50x109/L

Duration of Platelet Count ≥50x109/L

Maximum value

Maximum Increase from Baseline

Baseline-corrected AUEC
*All the above variables will be included in the listing. The number and percentage of responders
(for variables denoted with an asterisk) will be tabulated separately as described in 
Section 8.1.3.3.
Summary tabulations by dose arm will be repeated for the subgroups defined in Section 4.8
(based on the FAS only).
Mean and mean change from Baseline platelet values will be plotted versus scheduled visit by 
dose arm with all dose arms overlaid on the same plot. Similar plots will be provided for 
response rate over time (response, complete response and platelet count ≥50x109/L). Mean 
median, mean change and median change from Baseline total IgG results will be plotted over 
time by dose arm with all dose arms overlaid on the same plot.
Individual platelet and total IgG (including IgG subclasses, measured by ACM Global Central 
Laboratory) concentrations will be displayed graphically over time (Day 1 to Day 85 for Dose 
Arm 1; Day 1 to Day 71 for Dose Arm 2; Day 1 to Day 64 for Dose Arm 3 and Day 1 to Day 57 
for Dose Arms 4 and 5) for each subject (linear scale). The platelet and total IgG concentrations
will be overlaid on the same plot (discrete y-axes) with separate plots for each subject (2 lines 
per plot). Additional plots will be presented with the platelet and IgG subclasses overlaid on the 
same figure (5 lines per plot). All plots will include a vertical reference line to indicate when the 
last dose was administered for each subject. The mean (and median in a separate plot) change 
from baseline in platelet and the mean (median) change from baseline in total IgG concentrations 
will be overlaid on the same plot (discrete y-axes) with separate plots for each dose arm (2 lines 
per plot).
In addition scatter plots will be presented showing the Maximum value for platelet count versus 
the corresponding total IgG i.e., the value of total IgG at the time of the Maximum platelet value. 
All subjects will be included on the same plot with distinct symbols to distinguish the dose arms. 
This plot will be repeated for the Maximum platelet value versus percentage change in total IgG 
i.e., the percentage change from Baseline in total IgG at the time of the Maximum platelet value.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 37 of 128
8.1.3
Statistical analysis of platelets
8.1.3.1
Analysis of maximum increase from Baseline
In order to investigate if the average maximum increase from Baseline in platelet count is greater 
than zero, for dose arms with ≥10 subjects, a 1-sided one sample t-test will be performed at the 
5% level. For each dose arm the following null and alternative hypotheses will be tested:

H0: Average maximum increase from Baseline within dose arm is less than or equal to zero

H1: Average maximum increase from Baseline within dose arm is greater than zero
An assessment of the distribution of the maximum increase from Baseline in platelet count will 
be performed prior to the statistical analysis in order to check the validity of the proposed 
parametric analysis method. This will be based on visual inspection of histograms and 
quantile-quantile plots for each dose arm which will be included as part of the statistical 
appendices. If the data show a departure from normality, a non-parametric Wilcoxon signed rank 
test (1-sided) will be applied in addition to the t-test.
If the data are deemed to be normally distributed a parametric analysis will be performed using a 
one sample t-test. The mean maximum increase from Baseline, the 90% CI and the p-value 
obtained from the statistical analysis will be tabulated. In order for the null hypothesis (H0) to be 
rejected the p-value must be less than 5%.
Analyses will be performed for the FAS and repeated for the PPS.
8.1.3.2
Analysis of time to response
The time to first response will be analyzed with the log-rank test and displayed using Kaplan-
Meier curves.
Kaplan-Meier curves will be presented for the variables Time to Response, Time to Complete 
Response, and Time to Platelet Count ≥50x109/L. Descriptive statistics will include the p-value 
for the log-rank test for the equality over dose arms. The point estimate for the median number of 
days to response with 90% CIs will be given if estimable. Further a summary including the 
number and percent of censored subjects, the number of responders and total subjects by dose 
arm and in total will be given.
For the purpose of the analysis subjects with no response will be censored at the end of the study 
or at the date of withdrawal.
Analyses will be performed for the FAS and repeated for the PPS.
8.1.3.3
Analysis of responder rate
The number and percentage of subjects achieving a Response, Complete Response and Platelet 
Count ≥50x109/L will be summarized by dose arm at each scheduled post-Baseline visit. The 
90% CI for the percentage of responders will be included, calculated using a Wilson 
approximation. The tabulation will also include an overall summary (across all visits) of the 
number and percentage of subjects achieving a Response, Complete Response and Platelet Count 
≥50x109/L at any time during the study. For the purpose of the tabulation the lower and upper 
90% CI for the percentage of subjects will be truncated at 0 and 100% respectively.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 38 of 128
In addition the percentage of subjects achieving a Response, Complete Response and Platelet 
Count ≥50x109/L will be plotted at each post-Baseline visit. Separate plots will be presented for 
each response type with all dose arms overlaid on the same plot.
Analyses will be performed for the FAS and repeated for the PPS. Summary tabulations by dose 
arm will be repeated for the subgroups defined in Section 4.8 (based on the FAS only).
Percentage of days without bleeding will also be described by dose arm for each type of response 
(response, complete response and platelet Count >=50x10/L). Percentage of days without 
bleeding is calculated using the following formula:
((N of visits with a SMOG score – N of these visits where bleeding occurred) / N of visits with a 
SMOG score) x 100
In case rescue medications are taken, only the data up to the start date of rescue medication will 
be utilized for the summary tables. Listings will contain all the data but a footnote will be 
included indicating the patients for which some data has been excluded from the summary tables.
In case of partial dates, the imputation rules for partial dates described in Section 4.2.7 will be 
applied.
8.1.4
Rescue medication definition (after medical inspection)
In the rescue medication section of the protocol, rescue medication is defined as platelet 
substitution or treatment with a commercially available IVIg. In addition, the prohibited 
medications PLEX, dexamethasone and rituximab will also be considered as a rescue medication 
for analysis.
8.2
Other efficacy variables
8.2.1
ITP bleeding score
The ITP bleeding score is a consensus-based ITP-specific Bleeding Assessment Tool (ITP-BAT) 
based on a precise definition of bleeding manifestations and on the grading of their severity 
(Rodeghiero et al, 2013). The ITP bleeding score will be assessed using the ITP-BAT tool 
version 1.0 at the visits indicated in Section 2.2.2.
Bleeding manifestations will be grouped into 3 major domains, with gradation of severity 
(SMOG):

Skin (S)

Visible mucosae (M)

Organs (O)
Each bleeding manifestation is assessed at the time of examination and each domain is 
subcategorized into different types of bleeding. Severity is graded from Grade 0 to 3 or 4, with 
Grade 5 for any fatal bleeding. Bleeding reported by the subject without medical documentation 
is graded as 1. The worst bleeding manifestation since the last visit (or in the 15 days preceding 
the first visit) is graded for each bleeding type (within each domain), and the highest grade 
within each domain is reported as part of the SMOG.
The overall SMOG index will be reported as S2M2O3 for example. Intracranial bleeding will
always be reported, irrespective of its grade. For example, if a female subject had S2 
(subcutaneous hematoma) M2 (epistaxis) O3 (menorrhagia) and an intracranial bleeding Grade 2 
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 39 of 128
(post trauma, requiring hospitalization), the SMOG index is S2M2O3 (intracranial 2). If the same 
subject also had intracranial bleeding Grade 3, the SMOG index is S2M2O3 (intracranial 3).
Further details regarding the bleeding types and scoring algorithms are provided in Section 13.3.
The individual responses for the ITP bleeding score will be listed by dose arm and visit for those 
items related to the SMOG score. A separate listing will be presented for the bleeding history 
obtained at Screening including the date and results of any platelet counts (obtained outside the 
clinical study) together with any medications taken which may interfere with hemostasis; this
information will not form part of the SMOG score. Details of bleeding after surgery, invasive 
procedures and hemostatic challenges, including platelet counts associated with such procedures
will also be listed. This information will not form part of the SMOG score.
A separate listing of the grades for each bleeding type will be presented for each domain, and 
will include the overall score (highest grade) for the specific domain which will be used in the 
derivation of the SMOG.
The results for the ITP bleeding score will be summarized (n, median, minimum and maximum) 
by dose arm and visit (absolute values only) for each domain. In addition the number and 
percentage of subjects with severe or clinically relevant bleeding will be summarized at each 
visit. Clinically relevant bleeding is defined as follows:

Skin (S) severity of Grade 3

Mucosal (M) severity of Grade 2 or higher and/or

Organ (O) severity of Grade 2 or higher
The number and percentage of subjects with absence of bleeding at each visit will also be 
included in the summary. Absence of bleeding will correspond to a Grade 0 for each domain.
Summaries will be presented for both the FAS and the PPS.
8.2.1.1
ITP bleeding score and platelet response
In addition to the platelet response variables defined in Section 8.1.1 the following variables will 
also be defined based on a combination of platelet response and information from the ITP 
bleeding score (these will be referred to as Clinical Response variables). In case rescue 
medications or prohibited medications potentially affecting platelet counts are taken, only the 
platelet data up to the start date of rescue medication will be utilized for the summary tables 
(refer to Section 8.1.4):

Clinical Response: a Clinical Response is defined as a platelet count ≥30x109/L with at least 
2-fold increase from the Baseline value AND absence of bleeding, by visit. This must be 
confirmed by a second measurement at least 5 days later (to allow for the ±2-day visit 
window), showing a platelet count ≥30x109/L and at least 2-fold increase from the Baseline.

Time to Clinical Response is defined as the time from starting treatment (Day 1) to 
achievement of Clinical Response. The will be taken as the time to the first platelet 
assessment (obtained at the same time as the corresponding ITP bleeding score assessment). 
If the second assessment does not fulfill the required criteria for a clinical response, the 
subject will be considered as a nonresponder at the respective visits.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 40 of 128

Duration of Clinical Response: the duration of Clinical Response is defined as the time 
between achievement of a Clinical Response to the first time a loss of Clinical Response 
occurred (defined as platelet count <30x109/L or less than 2-fold increase from Baseline OR 
presence of bleeding). Refer to Section 8.1.1 in case a subject has several clinical responses 
or the clinical response is maintained until the end of the study".

Complete Clinical Response: a Complete Clinical Response is defined as a platelet count 
≥100x109/L AND absence of bleeding, by visit. This must be confirmed by a second 
measurement at least 5 days later (to allow for the ±2-day visit window), showing a platelet 
count ≥100x109/L.

Time to Complete Clinical Response: the time to Complete Clinical Response is defined as 
the time from starting treatment (Day 1) to achievement of Complete Clinical Response

Duration of Complete Clinical Response: the duration of Complete Clinical Response is 
defined as the time between achievement of a Complete Clinical Response to the first time a 
loss of Complete Clinical Response occurred (defined as platelet count <100x109/L OR
presence of bleeding). Refer to Section 8.1.1 in case a subject has several clinical responses 
or the clinical response is maintained until the end of the study".

No Clinical Response or a loss of clinical response: the platelet count must be defined as a 
platelet count <30x109/L OR >=30x109/L WITHOUT at least a 2-fold increase from the 
Baseline value OR presence of bleeding, by visit. This must be confirmed by a second 
measurement 1 to 9 days* later, showing a platelet count <30x109/L OR >=30x109/L
WITHOUT at least a 2-fold increase from the Baseline value.
For all the above response criteria, the calculation rules included in Section 8.1.1 will apply. In 
addition the following will be applicable:

The Clinical Response variables will be assessed only for visits for which both platelet 
counts and the ITP bleeding score are assessed. The last visit cannot be a clinical response as 
no confirmation after that is available.

Absence of bleeding is indicated by Grade 0 for all domains of the SMOG, or a Skin Grade 
of 0 or 1

Presence of bleeding is indicated by a Mucosae or Organs Grade of ≥1, or Skin Grade of ≥2
*This differs from the published definition (Rodeghiero et al, 2009) which requires 2 platelet 
measurements 1 day apart to define no response or loss of response. In the current protocol 
platelet count assessments are not as frequently planned (unless unscheduled measurements are 
performed), thus it was deemed appropriate to modify the definition above to take into account 
the schedule of assessments in this study. 
As a result the following clinical response variables are not in complete accordance with the 
guideline:

Duration of Clinical Response

Duration of Complete Clinical Response

No Clinical Response
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 41 of 128
All response variables described above will be listed by dose arm and subject and summarized 
by dose arm and visit where appropriate. The responder rates will be tabulated as described in 
Section 8.1.3.3. Moreover the change in category of bleeding from Baseline will also be 
presented in shift table at all post-Baseline visits by dose arm. Summary tabulations for Clinical 
Response by dose arm will be repeated according to past intravenous immunoglobulin 
medication (Yes/No) and the number of past ITP therapies (≤2/>2). All analyses described in this 
section will be performed for the FAS.
In case rescue medications are taken, only the data up to (not including) the start date of rescue 
medication will be utilized for the summary tables. Listings will contain all the data but a 
footnote will be included indicating the patients for which some data has been excluded from the 
summary tables. In case of partial dates, the imputation rules for partial dates described in 
Section 4.2.7 will be applied.
8.2.2
Patient reported outcomes
8.2.2.1
NFI-MS
The NFI-MS was developed in multiple sclerosis and consists of 23 items in four subscales:

Physical (8 items)

Cognitive (4 items)

Relief by diurnal sleep or rest (6 items)

Abnormal nocturnal sleep and sleepiness (5 items)
Each item is answered using a 4-point Likert scale according to the following:

0 = Strongly disagree

1 = Disagree

2 = Agree

3 = Strongly agree
Within each subscale a summary score is calculated by adding up the responses to each item, i.e., 
the summary score for the physical subscale ranges from 0 to 24. In addition, an overall 
summary score (ranging from 0 to 30) is calculated using specified items from the Physical and 
Cognitive subscales. The individual items and further detail regarding the scoring algorithm are 
presented in Section 13.2. A listing with the questionnaire glossary will be described.
The individual NFI-MS item results and calculated summary scores (for each subscale and for 
the Physical/Cognitive subscales) will be listed by dose arm and visit including changes from 
Baseline (Day 1, predose). Descriptive summaries (including n, arithmetic mean, median, SD, 
minimum and maximum) will be presented by dose arm and visit for both absolute values and 
changes from Baseline. Summaries will be presented for both the FAS and PPS.
Mean and change from Baseline values will be plotted over time by dose arm with all dose arms 
overlaid on the same plot, for both the FAS and PPS. Separate plots will be presented for each 
individual subscale and the Physical/Cognitive overall score.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 42 of 128
9
PHARMACOKINETICS AND PHARMACODYNAMICS 
9.1
Pharmacokinetics
Due to the blood sampling regimen there will be no calculation of PK parameters using standard 
methods eg, noncompartmental analysis. Population PK analysis may be conducted and will be 
described in a separate Data Analysis Plan and reported outside the CSR.
The actual blood sampling timepoints for UCB7665 concentration will be obtained relative to the 
start time of the first infusion. No time deviations will be calculated as the blood sampling is not 
scheduled at a specified timepoint at each visit.
Individual concentrations of UCB7665 will be listed by dose arm for the SS and will include the
actual sampling time in days relative to the first dose. The planned dose in mg will be calculated 
based on the body weight at Screening and the dose arm, and included in the listing. The actual 
dose administered will be calculated based on the planned dose and the percent of planned dose 
administered as follows:
Actual dose (mg) = Planned dose (mg)*Percent of planned dose administered
The percent of planned dose administered is calculated as described in Section 10.1. The actual 
dose will also be included in the concentration listing.
Individual concentrations will be summarized by dose arm and scheduled sampling day for the 
PK-PPS using n, arithmetic mean, median, SD, minimum, maximum, geoMean and 95% CI, 
geoCV (assuming log-normally distributed data).
For each subject, individual concentration versus time (day) profiles will be presented 
graphically in linear and semi-logarithmic scale. Individual plasma concentration versus time 
(day) profiles will also be displayed for each dose arm with all subjects within each dose arm 
overlaid on the same plot (linear and semi-logarithmic scale).
Geometric mean profiles of UCB7665 with corresponding lower and upper limit of the 95% CI 
(linear scale plot only) will also be presented with all dose arms overlaid on the same plot.
All figures will include the LLOQ on the semi-logarithmic plots.
The following rules will apply for PK data listings and summaries:

Values below the LLOQ will be reported as BLQ in the listings

Descriptive statistics of concentrations will be calculated if at most 1/3rd of the individual 
data points are missing or are not quantifiable (<LLOQ). Values that are BLQ will be 
replaced by the numerical value of the LLOQ/2 in this instance. However if n≤3, then only n, 
minimum and maximum will be presented. The other descriptive statistics will be left blank.

If no subjects have data, only n=0 will be presented. The other descriptive statistics will be 
left blank.
The 95% CI for the geoMean will be calculated by obtaining the lower and upper 95% CI for 
the arithmetic mean on the log-transformed data and back-transforming to obtain the 
respective values for the geoMean

The 95% CI lower and 95% CI upper should be left blank if the SD (or equivalently, the 
geoCV) is 0
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 43 of 128

The geoCV will be calculated using the following formula where SD is the standard 
deviation from the log-transformed data
geoCV (%) = sqrt[(exp (SD^2) – 1)] x 100
The above summaries will be repeated separately for the subjects in the PK/PD substudy sample, 
in the event of very few subjects (<5 subjects) only listings will be provided.
Further analyses and summaries relating to the population PK analyses and PK/PD analyses will 
be described in a separate SAP and reported separately.
9.2
Pharmacodynamics
The analysis of the PD data will be performed on the FAS with the exception of the total IgG and 
IgG subclasses, which will be analyzed on the PD-PPS. All listings will be presented for the SS.
The above summaries will be repeated separately for the subjects in the PK/PD substudy sample, 
in the event of very few subjects (<5 subjects) only listings will be provided.
9.2.1
ITP-specific autoantibodies
The following ITP-specific autoantibodies will be measured using the indirect MAIPA method 
and pre-chloroquine minus post chloroquine treated scores for PIFT
The results will be expressed in the form of the OD value and for indirect PIFT method using the 
following categories: 0 = negative; 0.5 = week positive; 1 = positive; 2 = positive; 3 = strong 
positive; 4 = strong positive.
ITP-specific autoantibodies (OD value and PIFT categories) will be listed by dose arm and 
timepoint. OD values that are ALD will be displayed as such in the listings.
Descriptive summaries (including n, arithmetic mean, median, SD, minimum and maximum)
will be presented by dose arm and visit for absolute values only. Any values that are ALD will 
be handled as described in Section 4.2.3 for the calculation of the descriptive statistics.
Mean values will be plotted over time by dose arm with all dose arms overlaid on the same plot
and separate plots for each variable. In addition, combined individual (spaghetti) plots will be 
plotted over time by dose arm for each variable (absolute values only). All subjects within each 
dose arm will be overlaid on the same plot.
In order to evaluate the relationship between changes in platelet count and total IgG, IgG 
subclasses and ITP-specific autoantibodies the following figures will be presented:

Spaghetti plot of individual ITP-specific autoantibodies and platelet counts (measured by 
ACM Global Central Laboratory) will be displayed graphically over time (Day 1 to Day 85 
for Dose Arm 1; Day 1 to Day 71 for Dose Arm 2; Day 1 to Day 64 for Dose Arm 3 and Day 
1 to Day 57 for Dose Arms 4 and 5) for each subject (linear scale). The ITP-specific 
autoantibodies
and platelet counts will be overlaid on the 
same plot (discrete y-axes) with separate plots for each subject (4 lines per plot)
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 44 of 128

A scatter plot of platelet counts (measured by ACM Global Central Laboratory) versus 
ITP-specific autoantibodies measured at the same visit will be presented in linear scale, with 
separate plots for each dose arm and for each variable 
All subjects and visits will be included on the same plot for each dose arm

Individual ITP-specific autoantibodies and total IgG (from ACM Global Central Laboratory)
will be displayed graphically over time (Day 1 to Day 85 for Dose Arm 1; Day 1 to Day 71 
for Dose Arm 2; Day 1 to Day 64 for Dose Arm 3 and Day 1 to Day 57 for Dose Arms 4 and 
5) for each subject (linear scale). The ITP-specific autoantibodies 
and total IgG will be overlaid on the same plot (discrete y-axes) with separate plots 
for each subject (4 lines per plot). These plots will be repeated for each of the IgG subclasses.
The plots versus time will include 2 y-axes with the ITP-specific autoantibodies on the left hand 
y-axis and the platelet counts (or total IgG and IgG subclasses) on the right hand y-axis. Only 
patients with positive ITP-specific autoantibodies will be described. 
All analyses described in this section will be performed on the FAS.
9.2.2
Total IgG and IgG subclasses
Total IgG concentrations (measured by ACM Global Central Laboratory) and IgG subclasses
will be listed by dose arm and visit including changes from Baseline and percentage changes 
from Baseline. Descriptive summaries (including n, arithmetic mean, median, SD, minimum and 
maximum) will be presented by dose arm and visit for absolute values, changes from Baseline 
and percentage changes from Baseline. The maximum decrease from Baseline in total IgG 
(absolute and percentage decrease) will be reported in the listing and summarized for each dose 
arm based on the results obtained from ACM Global Central Laboratory. Summary tabulations 
(for total IgG only) by dose arm will be repeated for the subgroups defined in Section 4.8.
In the event that a decrease from Baseline in total IgG is not observed in a given subject, the 
maximum decrease will be reported as the smallest increase from Baseline.
Mean, median, median change from Baseline and mean and median percentage change from 
Baseline values in total IgG (measured by ACM Global Central Laboratory) will be plotted over 
time by dose arm with all dose arms overlaid on the same plot. Additional figures will be 
presented in conjunction with the ADA results as described in Section 9.3.4 as well as figures in 
conjunction with the platelet results as described in Section 8.1.1.
Finally, a separate figure will be presented by subject showing the individual total IgG results 
from ACM Global Central Laboratory.
Any values that are BLQ or ALQ will be handled as described in Section 4.2.3.
All analyses described in this section will be performed on the PD-PPS. In case rescue 
medications are taken, only the IgG data up to the start date of rescue medication will be utilized 
for the summary tables. Listings will contain all the data but a footnote will be included 
indicating the patients for which some data has been excluded from the summary tables. In case 
of partial dates, the imputation rules for partial dates described in Section 4.2.7 will be applied.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 45 of 128
9.3
Other immunological variables
The analysis of the immunological data will be performed on the FAS. All listings will be 
presented for the SS.
9.3.1
Serum immunoglobulins and lymphocytes
Serum immunoglobulins (IgA, IgE and IgM) will be listed by dose arm and visit including 
changes from Baseline. Descriptive summaries (including n, arithmetic mean, median, SD, 
minimum and maximum) will be presented by dose arm and visit for both absolute values and 
changes from Baseline. The listing and summary tabulation will be repeated for B- and 
T-lymphocytes.
Mean and mean change from Baseline values will be plotted over time by dose arm with all dose 
arms overlaid on the same plot and separate plots for each variable (IgA, IgE, IgM, B- and 
T-lymphocytes).
Similar plots will be presented by dose arm for the mean and mean change from Baseline values 
in IgA, IgE, IgM and total IgG only. Separate plots will be presented for each dose arm with all 
variables overlaid on the same plot.
In addition, individual immunoglobulin (IgA, IgE, IgM and total IgG) values will be graphically 
displayed over time with all variables overlaid on the same plot and separate plots for each 
subject. 
For all overlaid plots for the immunoglobulin variables, discrete y-axes may be used for 
applicable variables to accommodate changes in the scale of measurement.
Any values are that BLQ or ALQ will be handled as described in Section 4.2.4.
All analyses described in this section will be performed on the FAS.
9.3.2
Serum and plasma complement levels
Serum (C3 and C4) and plasma (C3a and C5a) complement variables will be listed by dose arm 
and visit including changes from Baseline. Descriptive summaries (including n, arithmetic mean, 
median, SD, minimum and maximum) will be presented by dose arm and visit for both absolute 
values and changes from Baseline.
Mean and mean change from Baseline values will be plotted over time by dose arm with all dose 
arms overlaid on the same plot and separate plots for each variable.
Any values are that BLQ or ALQ will be handled as described in Section 4.2.4.
All analyses described in this section will be performed on the FAS.
9.3.3
Serum biomarkers
Serum safety biomarkers 
and BAFF will be listed by dose arm and timepoint including changes 
from Baseline. Descriptive summaries (including n, arithmetic mean, median, SD, minimum and 
maximum) will be presented by dose arm and timepoint for both absolute values and changes 
from Baseline.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 46 of 128
Mean and mean change from Baseline values will be plotted over time by dose arm with all dose 
arms overlaid on the same plot and separate plots for each variable.
Any values are that BLQ or ALQ will be handled as described in Section 4.2.4.
All analyses described in this section will be performed on the FAS.
9.3.4
Anti-drug antibodies
Immunological variables will be analyzed for all subjects in the SS. Anti-UCB7665 antibody 
data will be summarized at each scheduled visit, and the rate of ADA positive subjects will be 
calculated.
A calibrator screening assay measures ADA as relative mass units (RMU) in units/mL. A cut 
point will be determined by the bioanalytical laboratory that will be used to determine the status 
of ADA as above the cut point (ACP) or below the cut point (BCP). The RMU result from the 
calibrator screening assay will be used to report ADA levels.
For any ADA levels that are ACP, a further confirmatory assay will be performed, the results of 
which will be determined as either ‘confirmed positive’ (CP) or ‘not confirmed positive’ (NCP). 
The results for the ADA measurements will be listed by treatment group and time point based on 
the SS, including the screening assay, confirmatory assay and level in units/mL. 
The following definitions will be applied:

An ADA status of positive will be concluded for any subject with an ADA level that is ACP 
and CP at any time point 

An ADA status of negative will be concluded for any subject with an ADA level that is either 
BCP or ACP and NCP at any time point

A subject will be classified as having ADA positivity at Baseline if the Day 1, predose result 
is ACP and CP

A subject will be classified as having treatment-emergent ADA positivity when meeting one 
of the following criteria:

The Baseline result is either BCP or ACP and NCP, and at least one post-Baseline time 
point is ACP and CP

The Baseline result is positive (ACP and CP) and at least one post-Baseline measurement 
shows a pre-defined fold increase in units/mL from the Baseline value (the fold increase 
from Baseline required to meet this criterion will be defined with the development of the 
assay and will be included in the TFLs)

A subject will be classified as overall positive if at least one post-Baseline measurement is 
ACP and CP (this includes subject who have negative results at Baseline)

A subject will be classified as overall negative if at all post-Baseline visits the ADA status is 
negative (this includes subjects who have positive [ACP and CP] results at Baseline)

Inconclusive: pre-ADA negative or pre-ADA positive subjects with negative ADA samples 
post baseline for which time matched drug levels are above the demonstrated drug tolerance 
characteristics of the ADA screening assay at one or more sampling time points
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 47 of 128

Missing: relevant samples are missing
The ADA status (positive/negative) will be summarized as a categorical endpoint (number and 
percentage of subjects) for all time points and overall, based on the SS. 
In addition, the first occurrence of treatment-emergent ADA positivity (based on the definitions 
above) will be summarized (number and percentage of subjects) at each post-Baseline visit, 
based on the SS. This tabulation will count the number of subjects at each post-Baseline visit 
who fulfill at least one of the above defined criteria for treatment-emergent positivity; subjects 
will be counted in the numerator based on the earliest visit at which one of these criteria is 
fulfilled. At other visits, subjects will be counted in the denominator (assuming a measurement is 
available). For all tabulations, percentages will be based on the number of observations at each 
visit.
A separate listing will be presented (based on the SS) showing the UCB7665 concentrations and 
ADA measurements in the same output in adjacent columns. The listing will include the 
UCB7665 concentration, ADA status (ACP or BCP) and confirmatory assay results if applicable 
(NCP or CP), together with the units/mL for results that are CP. In addition the time since the 
previous administration of IMP will be reported (in days).
Finally, individual subject plots (based on the SS) will be presented displaying the ADA 
units/mL and UCB7665 concentrations overlaid on the same figure. The figure will also show 
the timing and dose of each administration of UCB7665 received during the study.
The rules for handling values that are BLQ in the UCB7665 concentration data are described in 
Section 4.2.5 For the ADA data, any negative results for which there are no units/mL available at 
a specific visit will be substituted with 0.001 for the purpose of the figure.
9.3.5
Cytokines
Cytokines will be obtained at Baseline in all subjects and at subsequent visits only in subjects 
experiencing severe infusion reactions (or due to DMC’s or sponsor’s request). Only for subjects 
for whom additional measurements were obtained the results of the cytokine assessments will be 
listed by dose arm and timepoint including changes from Baseline. 
If appropriate (i.e., sufficient data are available), summaries will be presented by dose arm and 
timepoint for both absolute values and changes from baseline. Depending on the availability of 
data, it may be also decided to summarize the data overall without stratification by dose arm.
A minimum of 5 subjects per dose arm with any post-dose cytokine measurements will be 
required in order to produce summaries by dose arm. Similarly, a minimum of 5 subjects across 
all dose arms with any post-dose cytokine measurements will be required to produce the 
summaries without stratification by dose arm. 
The cytokines to be measured are presented in Section 13.4.
All analyses described in this section will be performed on the FAS.
10
SAFETY ANALYSES
All safety analyses will be presented using the SS. Listing will be presented by dose arm and 
subject; tabulations will be presented by dose arm and overall (AE data only), with the lowest 
dose per kg presented first and continuing in ascending order.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 48 of 128
10.1
Extent of exposure
All drug administration details (including date, start and stop time of infusion, location of 
infusion site, interruptions, discontinuations [including reasons] and volume delivered) will be 
listed. The duration of the infusion, in minutes, will also be calculated.
The percent of planned dose administered will be calculated based on the actual volume 
delivered as follows:
Percent of Planned Dose Administered (%) = [100*(Actual volume/Planned volume)]
For all subjects the planned volume is 10mL.
The overall exposure to UCB7665 will be calculated in days as follows and listed for each 
subject:
Total exposure (days) = (Date of last dose – Date of first dose) + 1
The planned dose regimens are as follows:

Subjects in Dose Arm 1 will receive 5 sc doses of UCB7665 4mg/kg at 1-week intervals

Subjects in Dose Arm 2 will receive 3 sc doses of UCB7665 7mg/kg at 1-week intervals

Subjects in Dose Arm 3 will receive 2 sc doses of UCB7665 10mg/kg at 1-week intervals

Subjects in Dose Arm 4 will receive 1 sc dose of UCB7665 15mg/kg 

Subjects in Dose Arm 5 will receive 1 sc doses of UCB7665 20mg/kg 
The DMC may decide to modify the dosing regimen following review of emerging safety data. 
In this case the modified dose regimen will be considered as a new dose arm for the study.
10.2
Adverse events
Adverse events will be recorded from the time of informed consent until study completion. All 
AEs will be coded (Section 3.8) and will be categorized by relationship to UCB7665.
In addition, AEs will be classified according to the CTCAE Version 4.03 for severity. For any 
AEs where it is not possible to provide a CTCAE grading, the events will be assessed using a 
standard intensity classification (mild, moderate and severe). For the purpose of the tabulations 
all CTCAE severity classifications will be mapped to a mild/moderate/severe grade as described 
in the below sections. Bleeding events classified as Grade 1 or Grade 2 (based on CTCAE) will 
not be reported as AEs as these will be assessed and reported as part of the ITP-BAT 
assessments. Bleeding events classified as Grade 3 or higher, based on CTCAE, will be reported 
as AEs.
A TEAE is defined as any event that was not present prior the first administration of UCB7665
or any unresolved event already present before the first administration of UCB7665 that worsens 
in intensity following exposure to treatment. Adverse events starting before the first 
administration of UCB7665 or after 8 weeks following the final dose of UCB7665 will not be 
considered as TEAEs. Such events will be listed only.
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent. 
Handling of missing dates/times for classification of AEs as TEAEs is described in Section 4.2.7.
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 49 of 128
The following rules will be used to assign a TEAE to a study period:

A TEAE will be assigned to the Dosing Period for the tabulations if the start date/time of the 
event is at the time of or after the first administration of UCB7665 until 7 days after the final 
dose; for the purpose of the analysis this will be calculated as the start date/time of the final 
infusion plus 168 hours;

A TEAE will be assigned to the Observation Period for the tabulations if the start date/time 
of the event is greater than 7 days after the final dose until 8 weeks following the final dose; 
events starting later than 8 weeks following the final dose of UCB7665 are not considered as 
TEAEs.
Adverse events with missing start date/times will be handled as described in Section 4.2.7 for 
this classification.
The number and percentage of subjects who experience TEAEs will be summarized for each
dose arm and overall. The following summaries will be presented:

Incidence of TEAEs (overview including number and percentage of subjects with any 
TEAEs, serious TEAEs, discontinuations due to TEAEs, TEAEs leading to permanent 
withdrawal of UCB7665, related TEAEs, TEAEs with CTCAE Grade 3 and above [or rated 
as ‘severe’ for events with no CTCAE classification], and deaths; event counts will also be 
included)

Incidence of TEAEs (overview as described above) during the Dosing Period

Incidence of TEAEs by SOC, HLT and PT

Incidence of TEAEs during the Dosing Period by SOC, HLT and PT

Incidence of serious TEAEs by SOC, HLT and PT

Incidence of non-serious TEAEs by SOC, HLT and PT

Incidence of AEs of special interest by SOC, HLT and PT

Incidence of AEs of interest by SOC, HLT and PT

Incidence of TEAEs by relationship, SOC, HLT and PT 

Incidence of serious TEAEs by relationship, SOC, HLT and PT

Incidence of non-serious TEAEs by relationship, SOC, HLT and PT

Incidence of fatal TEAEs by relationship, SOC, HLT and PT

Incidence of TEAEs by maximum relationship, SOC, HLT and PT

Incidence of TEAEs by maximum intensity (mild, moderate and severe), SOC, HLT and PT

Incidence of non-serious TEAEs above threshold of 5% of subjects by SOC and PT

Incidence of non-serious TEAEs above threshold of 5% of subjects by relationship, SOC and 
PT

Discontinuation due to AEs
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 50 of 128
Summary tables will contain counts of subjects, percentages of subjects in parentheses and the 
number of events where applicable. A subject who has multiple events in the same SOC, HLT
and PT will be counted only once in the subject counts but all events will be included.
In summaries including relationship to UCB7665, the following relationship categories will be 
included:

Related

Not related
Subjects who experience the same event multiple times will be included in the most related 
category for tabulations by maximum relationship. Events with missing relationship will be 
considered as ‘Related’ to the UCB7665 for summary purposes but shown as missing in the data 
listings.
In summaries including intensity, the CTCAE categories will be summarized according to the 
following categories:

Grade 1: Mild

Grade 2: Moderate

Grade 3: Severe

Grade 4: Severe

Grade 5: Severe
These will be tabulated together with the AEs that were not classified according to CTCAE 
criteria i.e., all Grade 1 AEs as per CTCAE criteria will be included in the ‘mild’ category 
together with those AEs classified as mild as per the ‘standard’ intensity classification.
Subjects who experience the same event multiple times will be included in the most severe 
category for tabulations by maximum intensity. Events with missing intensity will be considered 
as ‘Severe’ for summary purposes. All data will be presented as recorded in the database for the 
listings. 
Adverse event summaries will be ordered by alphabetical SOC, alphabetical HLT within SOC 
and decreasing frequency of PT in the overall column for tables including event counts. For 
tables including only number and percentage of subjects, summaries will be ordered by 
alphabetical SOC, alphabetical HLT within SOC and decreasing incidence of PT within SOC in 
the overall column.
A listing of all AEs will be presented by subject and dose arm. The listing will include the onset 
date/time and outcome date/time of the event (including relative days), the AE duration, days 
since first dose of UCB7665, days since most recent dose of UCB7665, pattern of event, 
severity/intensity, relationship, action taken and outcome. In addition the listing will flag AEs 
that led to discontinuation, TEAEs, AEs of interest, AEs of special interest, infusion reactions, 
SAEs, Sampson criteria and CTCAE grade.
10.3
Clinical laboratory evaluations
Laboratory data (chemistry [excluding follicle stimulating hormone, FSH], hematology, 
coagulation and urinalysis) and changes from Baseline (if applicable) for numeric variables will 
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 51 of 128
be listed by dose arm and visit. Any laboratory measurements that are BLQ or ALQ will be 
handled as described in Section 4.2.2. Values outside the reference range for the numeric 
variables will be flagged in the listings and in addition, results considered as markedly abnormal 
laboratory results (CTCAE Grade 3 and above) will be listed separately. The reference ranges 
will also be reported in the listings.
Chemistry [excluding FSH], hematology and coagulation variables will be summarized by dose 
arm at each visit, for both absolute values and changes from Baseline.
Laboratory variables will be grouped according to the laboratory function panel (Table 10-1) and 
categorized as normal, high or low, if applicable, based on the reference range supplied by the 
analytical laboratory. For selected variables that are identified in Table 10-1, the change in 
category from Baseline will be presented in shift tables at all post-Baseline visits.
Table 10‒1: Clinical laboratory measurements
Category
Panel
Variable
Serology
Serology
HIV, HBsAg, anti-HBs, anti-HBc, anti-HCV
Hematology
Red blood cell
RBC counta, hemoglobina, hematocrit
Platelet
Plateletab
White blood cell
WBC counta
White blood cell 
differential
Absolute counts: ANCa, basophilsa, eosinophilsa, 
ALCa, monocytesa
Percentages: neutrophils/leukocytesa, 
basophils/leukocytesa, eosinophils/leukocytesa, 
lymphocytes/leukocytesa, monocytes/leukocytesa.
Coagulation
Coagulation
INRa, prothrombin timea, aPTTa, fibrinogena
Chemistry
Electrolytes
Sodiuma, chloridea, potassiuma
Minerals
Calciuma, phosphatea, magnesiuma
Kidney function
BUNa, creatininea
Proteins
Total proteina, albumina, α1-globulina, α2-globulina, 
β-globulina, gamma globulina.
For all parameters except total protein, both absolute 
and percentage values will be reported as part of the 
serum protein electrophoresis.
Liver function
ASTa, ALTa, GGTa, ALPa, LDHa, total bilirubina, 
direct bilirubin (if indicated)
Lipids
Total cholesterola, triglyceridesa
Hormones
FSH
Other
hsCRPa, amylasea
Urinalysis
Dipstick
pHa, protein, glucose, ketones, urobilinogen, bilirubin, 
blood, nitrite, leucocytes
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UCB
28 Jan 2019
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 52 of 128
Category
Panel
Variable
Quantitative
Albumin, creatinine
Urine sedimentc
RBC, WBC. epithelial cells, casts, crystals, yeast, 
bacteria, amorphous urates, amorphous phosphates
Pregnancy test
Urine HCGd, serum HCGe
Other
HbA1c
ALC=absolute lymphocyte count; ALP=alkaline phosphatase; ALT=alanine aminotransferase; ANC=absolute 
neutrophil count; anti-HBc=hepatitis B core antibody; anti-HBs=hepatitis B surface antibody; anti-HCV=hepatitis C 
virus antibody; aPTT=activated partial thromboplastin time; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; FSH=follicle stimulating hormone; GGT=gamma-glutamyltransferase; HbA1c=glycosylated hemoglobin; 
HBsAg=hepatitis B surface antigen; HCG=human chorionic gonadotropin; HIV=human immunodeficiency virus; 
hsCRP=high sensitivity C-reactive protein; INR=International Normalized Ratio; LDH=lactate dehydrogenase; 
RBC=red blood cell; TB=tuberculosis; WBC=white blood cell.
a Shift tables will be presented for these variables. 
b Only platelet results measured at the local laboratory will be included in the safety outputs. Measurements 
obtained at the central laboratory will be reported as part of the efficacy analyses.
c If indicated, based on results of urine dipstick.
d Urine pregnancy test will be performed predose on dosing days and at the End-of-Study Visit
e Serum pregnancy test is done at Visit 1 (Screening) and to confirm results of positive urine test if applicable.
The number and percentage of subjects with markedly abnormal laboratory results (CTCAE 
Grade 3 and above) will be tabulated by dose arm and laboratory variable at each visit. The 
criteria for identifying abnormal laboratory results are detailed in Section 13.5. 
Figures of mean and mean change from Baseline will be plotted over time by dose arm for all 
quantitative laboratory variables (with the exception of any variables measured only at Screening 
and/or Baseline, eg serology, HbA1c and FSH), with all dose arms overlaid on the same plot.
The reference range for each variable (male and female, if applicable) will be included on the 
plot for absolute values. For the differential WBC counts, figures will be presented based on 
percentage values only.
Any additional laboratory variables not included in the outputs described previously (including 
pregnancy testing, FSH and serology) will be listed separately.
Finally, in order to provide a comparison between the platelet counts measured locally and 
centrally, a separate listing will be presented including only the observed platelet counts from 
each laboratory at each visit where both measurements are obtained. Difference between 
laboratories will also be presented.
10.3.1
Potential drug-induced liver injury
Subjects who meet any of the following criteria at a given timepoint will be listed:

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) increase ≥5xupper 
limit of normal (ULN)

ALT or AST increase ≥3xULN and total bilirubin ≥2xULN

ALT or AST increase ≥3xULN who exhibit temporally associated symptoms of hepatitis or 
hypersensitivity.
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Statistical Analysis Plan
UCB7665
TP0001
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Page 53 of 128

ALT or AST increase ≥3xULN (and ≥2xBaseline) and <5xULN, with total bilirubin 
<2xULN

ALT or AST increase ≥5xULN (and ≥2xBaseline), with total bilirubin <2xULN and no 
eosinophilia (i.e., ≤5%), with no fever, rash, or symptoms of hepatitis

Alkaline phosphatase (ALP) ≥2xULN
A summary of subjects who met the criteria for potential drug-induced liver injury (PDILI) will 
be presented together with any additional relevant data collected, if applicable.
10.4
Vital signs, physical findings, and other observations related to 
safety
10.4.1
Vital signs
The following vital signs measurements will be obtained:

Pulse rate

Systolic and diastolic blood pressure

Temperature 

Respiratory rate
A by-subject listing of all vital sign measurements and change from Baseline will be presented 
by dose arm and timepoint. The listing will include a flag for measurements identified as 
treatment-emergent markedly abnormal (TEMA)/potentially clinically significant (PCS) as 
calculated by the criteria outlined in Table 10‒2.
Descriptive statistics will be reported for all vital sign measurements. Measured values and 
changes from Baseline will be summarized by vital signs variable and timepoint for each dose 
arm. 
Figures of mean change from Baseline will be presented for each variable by dose arm. All dose 
arms will be overlaid on the same plot.
The number and percentage of subjects with TEMA/PCS vital sign values will be summarized by 
dose arm at each timepoint.
Table 10‒2: TEMA/PCS criteria for vital signs
Variable
Unit
Low
High
Systolic blood pressure
mmHg
Value <90 and ≥20 
decrease from Baseline
Value >180 and ≥15
increase from baseline
Diastolic blood pressure
mmHg
Value <50 and ≥15 
decrease from Baseline
Value >105 and ≥15 
increase from Baseline
Note: The change in measurement (increase or decrease) will be calculated relative to the value obtained at Baseline.
aBoth conditions must be satisfied for a measurement to be considered PCS.
Repeated and unscheduled measurements will be handled as described in Section 4.3.
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10.4.2
Electrocardiograms 
All standard 12-lead ECG recordings will be taken in triplicate with the subject resting in the 
supine position for at least 15 minutes and before obtaining any blood samples. The following 
variables will be reported:

Heart rate

RR interval

PQ/PR interval

QRS duration

QT interval

QT corrected for heart rate using Fridericia’s formula (QTcF = QT/RR0.33)
The individual measurements and the mean of the triplicate measurements will be reported in the 
by-subject listings. The listing will also include the change from Baseline and percentage change 
from Baseline (based on the mean of the triplicate measurements at each timepoint). TEMA/PCS 
ECG values will be flagged in the listing.
Measured values, changes, and percentage changes from Baseline will be summarized by dose 
arm at each timepoint and by ECG variable (based on the mean of the triplicate values at each 
visit). Mean change from Baseline and percentage change from Baseline in QTcF will be 
displayed graphically over time by dose arm, with all dose arms overlaid on the same plot.
The following cut-points in QTcF (raw data and change from Baseline) based on the mean of the 
triplicate data will be summarized categorically (number and percentage of subjects) by dose arm
at each visit.
For raw data:

<450msec

≥450 to <480msec

≥480 to <500msec

≥500msec
Change from Baseline in QTcF:

<30msec

≥30 to <60msec

≥60 msec
ECG findings for the individual triplicate measurements will be listed separately.
Repeated and unscheduled measurements will be handled as described in Section 4.3.
The number and percentage of subjects with TEMA/PCS ECG values will be summarized by 
dose arm at each visit.
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Table 10‒3: TEMA/PCS criteria for ECG
Variable
Criteria
QT corrected for heart rate using 
Fridericia’s formula (QTcF)
≥501ms
OR
≥60ms compared to baseline
PR prolongation
≥210ms and ≥10ms change from 
baseline
10.4.3
Other safety variables
Body weight will be listed by subject and visit. Subjects with abnormalities in the physical 
examination will be listed including details of the abnormality.
11
OTHER ANALYSES 
Subjects who experience severe headaches will complete a headache questionnaire followed by a 
neurological assessment (including fundoscopy). This will be performed daily until resolution. 
Additionally, a computed tomography (CT) or magnetic resonance imaging (MRI) scan, and 
lumbar puncture (LP) for CSF collection may be performed if indicated at the discretion of the 
Investigator.
The neurological assessment will include general appearance and, if indicated, assessments of 
cranial nerves, motor system examination, reflexes, coordination and fundoscopy. Each 
parameter within each body system (with the exception of fundoscopy) will be assessed as 
normal, abnormal not clinically significant or abnormal clinically significant. For the fundoscopy 
assessment, the result will be assessed as normal or abnormal, and the specific abnormalities will 
be documented in the CRF.
The results of the CT scan (or MRI) will be reported including the date and time of the 
assessment and the evaluation (normal, abnormal not clinically significant, or abnormal 
clinically significant).
The assessments to be performed from the CSF collection will include the following biomarkers:

Assessment of CSF/serum albumin quotients

Assessment of CSF/serum IgG quotients

Labile mediators such as the prostanoids

Soluble intercellular adhesion molecule-1 (ICAM-1) and histamine


Transforming growth factor-beta (TGFβ)

IL-10/CSF/serum IL-10 quotients
Symptoms and frequency of severe headache questionnaire glossary will be listed. The results of 
the headache questionnaire, neurological examination and any additional tests performed
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Statistical Analysis Plan
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(CT/MRI scan, fundoscopy and LP for CSF collection) will be listed for each subject. No 
summary tabulations will be provided for these assessments.
There will be an exit interview performed for all subjects at the end of the study. The results of 
the exit interview will be reported to UCB and not included in the TFLs as part of the CSR.
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Statistical Analysis Plan
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Page 57 of 128
12
REFERENCES
Robak T, Salama A, Kovaleva L, Vyhovska Y, Davies SV, Mazzucconi MG, et al. Efficacy and 
safety of Privigen®, a novel liquid intravenous immunoglobulin formulation, in adolescent and 
adult patients with chronic immune thrombocytopenic purpura. Hematology. 2009;14(4):227-36.
Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, et al.
Standardization of bleeding assessment in immune thrombocytopenia: report from the
International Working Group. Blood. 2013;121(14):2596-606.
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization 
of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults 
and children: report from an international working group. Blood. 2009; 113(11):2386-93.
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14
AMENDMENTS TO THE STATISTICAL ANALYSIS PLAN
14.1
Amendment 1
14.1.1
Rationale for the amendment
This SAP was amended following global protocol amendment 3 dated 15 February 2017 and 
local protocol amendments 3.5 (Georgia and Bulgaria) dated 23 August 2017 and 3.6 (Moldova) 
dated 7 September 2017. The main changes were to include three additional cohorts and a non-
mandatory genomic substudy. Other changes were made in line with the protocol amendment 
and all changes are detailed in the sections below.
The list of abbreviations was updated as required and a few other minor formatting updates were 
made.
All of the changes that were made in previous version of the SAP amendment 1 that are still 
applicable to the current version will be included in this section. 
14.1.2
List of changes
Specific changes
Change #1
Introduction (Section 1)
This SAP is based upon, and assumes familiarity, with the following documents:

Final Protocol: 09 November 2015

Protocol Amendment 0.1 (Moldova): 18 November 2015

Protocol Amendment 0.2 (Germany): 12 January 2016

Protocol Amendment 0.3 (Poland): 23 May 2016

Protocol Amendment 0.4 (Romania): 11 August 2016

Protocol Amendment 1 (Global): 19 May 2016

Protocol Amendment 1.1 (Moldova): 23 May 2016

Protocol Amendment 1.3 (Poland): 09 June 2016
Has been changed to:
This SAP is based upon, and assumes familiarity, with the following documents:

Final Protocol: 09 November 2015

Protocol Amendment 0.1 (Moldova): 18 November 2015

Protocol Amendment 0.2 (Germany): 12 January 2016

Protocol Amendment 0.3 (Poland): 23 May 2016

Protocol Amendment 0.4 (Romania): 11 August 2016

Protocol Amendment 1 (Global): 19 May 2016
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
Protocol Amendment 1.1 (Moldova): 23 May 2016

Protocol Amendment 1.3 (Poland): 09 June 2016

Protocol Amendment 2.0 (Global; not implemented): 21 October 2016

Protocol Amendment 3.0 (Global): 15 February 20117

Protocol Amendment 3.1 (Moldova): 08 March 2017

Protocol Amendment 3.3 (Poland): 07 March 2017

Ptoeocol Amendment 3.4 (Romania): 10 March 2017

Protocol Amendment 3.5 (Georgia and Bulgaria): 23 August 2017

Protocol Amendment 3.6 (Moldova): 07 September 2017
Change #2
Introduction (Section 1)
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP will be amended accordingly. In addition, if analysis definitions have to be 
modified or updated prior to database lock, a SAP amendment will be required. If, after database 
lock, additional analyses are required to supplement the planned analyses described in this SAP, 
these changes will be described in the CSR together with the associated rationale. The content of 
this SAP is compatible with the International Council for Harmonisation (ICH)/Food and Drug 
Administration (FDA) E9 Guidance documents.
Has been changed to:
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP amendment will be updated accordingly. In addition, if analysis definitions 
have to be modified or updated prior to database lock, a further SAP amendment will be 
required. If, after database lock, additional analyses are required to supplement the planned 
analyses described in this SAP, these changes will be described in the CSR together with the 
associated rationale. The content of this SAP is compatible with the International Council for 
Harmonisation (ICH)/Food and Drug Administration (FDA) E9 Guidance documents.
Change #3
Exploratory objectives (Section 2.1.3)
The following objectives have been added:

To evaluate the genomic components of ITP to understand the molecular etiology, 
progression, and treatment of the disease, applicable only for subjects consenting to
participate in the optional genomic analyses substudy

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Statistical Analysis Plan
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Page 78 of 128
Change #4
Other safety variables (Section 2.2.1.2)
The other safety variables are:

Vital sign values and change from Baseline (systolic and diastolic blood pressure, 
temperature, pulse rate, respiratory rate and body weight) to each visit in the Dosing Period 
and in the Observation Period up to Day 85 in the 4mg/kg dose arm and up to Day 71 in the 
7mg/kg dose arm. Body weight is measured only at Screening and Day 85 or Day 71 in the 
4mg/kg and 7 mg/kg dose arm respectively

12-lead electrocardiogram (ECG) parameters and change from Baseline to each dosing visit 
in the Dosing Period and to Day 36 and Day 85 in the Observation Period in the 4mg/kg dose 
arm, and at Day 22 and Day 71 in the Observation Period in the 7mg/kg dose arm

Laboratory values and change from Baseline (hematology including coagulation parameters, 
clinical chemistry, and urinalysis) to each visit in the Dosing Period and in the Observation 
Period up to Day 85 in the 4mg/kg dose arm and up to Day 71 in the 7mg/kg dose arm

TEAEs leading to withdrawal of investigational medicinal product (IMP)
Has been changed to:
The other safety variables are:

Vital sign values and change from Baseline (systolic and diastolic blood pressure, 
temperature, pulse rate and respiratory rate) to each visit in the Dosing Period and in the 
Observation Period up to Day 85 in Dose Arm 1 (4mg/kg once weekly [QWK]), up to Day 
71 in Dose Arm 2 (7mg/kg QWK), up to Day 64 in Dose Arm 3 (10mg/kg QWK) and up to 
Day 57 in Dose Arms 4 (15mg/kg) and 5 (20mg/kg). Body weight is measured only at 
Screening and at the corresponding EOS visit as outlined in the protocol

12-lead electrocardiogram (ECG) parameters and change from Baseline to each dosing visit 
in the Dosing Period and to Day 36 and Day 85 in the Observation Period in Dose Arm 1, to 
Day 22 and Day 71 in the Observation Period in Dose Arms 2, to Day 15 and Day 64 in Dose 
Arm 3 and to Day 8 and Day 57 in Dose Arms 4 and 5

Laboratory values and change from Baseline (hematology including coagulation parameters, 
clinical chemistry, and urinalysis) to each visit in the Dosing Period and in the Observation 
Period up to the corresponding EOS visit as outlined in the protocol

Values and change from Baseline in concentrations of total protein, albumin, α-globulin, and 
β-globulin to each visit in the Dosing Period and in the Observation Period up to Day 85 in 
Dose Arm 1, up to Day 71 in Dose Arm 2, up to Day 64 in Dose Arm 3 and up to Day 57 in 
Dose Arm 4 and 5

TEAEs leading to withdrawal of UCB7665

Change from Baseline in serum biomarkers 
 to each visit in the Dosing Period and up to Day 71 in the 
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07 Nov 20168
Statistical Analysis Plan
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TP0001
Confidential
Page 79 of 128
Observation Period in Dose Arm 1, up to Day 57 in the Observation Period in Dose Arm 2, 
up to the last visit prior to the corresponding EOS visit as outlined in the protocol
Change #5
Efficacy variables (Section 2.2.2)

Baseline-corrected area under the effect curve (AUEC) for platelet count calculated from 
Baseline to the end of study visit (Day 85 in the Observation Period in the 4mg/kg dose arm 
and Day 71 in the Observation Period in the 7mg/kg dose arm)

Assessment of ITP bleeding score over time at Baseline and at each dosing visit in the 
Dosing Period and to Day 36, Day 50, Day 64 and Day 85 in the Observation Period in the 
4mg/kg dose arm, and to Day 22, Day 36, Day 50 and Day 71 in the Observation Period in 
the 7mg/kg dose arm

Value and change from Baseline in Neurological Fatigue Index for Multiple Sclerosis 
(NFI-MS) summary score to Day 36, Day 50, Day 64 and Day 85 in the Observation Period 
in the 4mg/kg dose arm and to Day 22, Day 36, Day 50 and Day 71 in the Observation 
Period in the 7mg/kg dose arm
Has been changed to:

Baseline-corrected area under the effect curve (AUEC) for platelet count calculated from 
Baseline to the end of study visit (Day 85 in the Observation Period in Dose Arm 1, Day 71 
in the Observation Period in Dose Arm 2, Day 64 in the Observation Period in Dose Arm 3 
and Day 57 in Observation Period in Dose Arms 4 and 5)

Assessment of ITP bleeding score over time at Baseline and at each dosing visit in the 
Dosing Period and to Day 36, Day 50, Day 64 and Day 85 in the Observation Period in Dose 
Arm 1, to Day 22, Day 36, Day 50 and Day 71 in the Observation Period in Dose Arm 2, to 
Day 15, Day 29, Day 43 and Day 64 in the Observation Period in Dose Arm 3 and to Day 8, 
Day 22, Day 36 and Day 57 in the Observation Period in Dose Arms 4 and 5

Value and change from Baseline in Neurological Fatigue Index for Multiple Sclerosis 
(NFI-MS) summary score to Day 36, Day 50, Day 64 and Day 85 in the Observation Period 
in Dose Arm 1, to Day 22, Day 36, Day 50 and Day 71 in the Observation Period in Dose 
Arm 2, to Day 15, Day 29, Day 43 and Day 64 in the Observation Period in Dose Arm 3 and 
to Day 8, Day 22, Day 36 and Day 57 in the Observation Period in Dose Arms 4 and 5
Change #6
Efficacy variables (Section 2.2.2)
Some variables have been re-ordered to align with the order in the protocol.
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 80 of 128
Change #7
Pharmacokinetic variable (Section 2.2.3.1)

Plasma concentration of UCB7665 over time, at each visit during the Dosing Period and 3 
and 7 days following the last dose of UCB7665
Has been changed to:

Plasma concentration of UCB7665 over time, at each visit during the Dosing Period and 3 
and 7 days following the last dose of UCB7665 in each dose arm
Change #8
Pharmacokinetic variable (Section 2.2.3.1)
The following bullet point has been added at the end of this section:

Additional blood samples for the optional PK/PD substudy (early blood sampling) will be 
drawn at Visit 2 (predose and 4 hours after end of infusion on Day 1), Visit 2a (24 and 36 
[optional] hours after the start of Day 1 UCB7665 infusion) and Visit 2b (48 hours after the 
start of Day 1 UCB7665 infusion).
Change #9
Pharmacodynamic variables (Section 2.2.3.2)

Value and change from Baseline (absolute and percentage) in total IgG concentrations 
(measured by ACM Global Central Laboratory) to each visit in the Dosing Period and in the 
Observation Period up to Day 85 in the 4mg/kg dose arm and up to Day 71 in the 7mg/kg 
dose arm

Value and change from Baseline in total and endogenous IgG (measured via IgG depletion 
assay by LGC) to each visit in the Dosing Period and to Day 32, Day 36, Day 43, Day 57, 
Day 71 and Day 85 in the Observation Period in the 4mg/kg dose arm, and to Day 18, Day 
22, Day 29, Day 43, Day 57 and Day 71 in the Observation Period in the 7mg/kg dose arm

ITP-specific autoantibodies in serum 
 over time, 
measured at Day 1, Day 36 and Day 85 in the 4mg/kg dose arm and at Day 1, Day 22 and 
Day 71 in the 7mg/kg dose arm

Change from Baseline in IgG subclass concentrations (measured by ACM Global Central 
Laboratory) to each visit in the Dosing Period and in the Observation Period up to Day 85 in 
the 4mg/kg dose arm and up to Day 71 in the 7mg/kg dose arm
Has been changed to:

Value and change from Baseline (absolute and percentage) in total IgG concentrations 
(measured by ACM Global Central Laboratory) to each visit in the Dosing Period and in the 
Observation Period up to Day 85 in Dose Arm 1, up to Day 71 in Dose Arm 2, up to Day 64 
in Dose Arm 3 and up to Day 57 in Dose Arms 4 and 5

Value and change from Baseline in total IgG (measured via IgG depletion assay by LGC) to 
each visit in the Dosing Period and to Day 32, Day 36, Day 43, Day 57, Day 71 and Day 85 
in the Observation Period in Dose Arm 1, to Day 18, Day 22, Day 29, Day 43, Day 57 and 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 81 of 128
Day 71 in the Observation Period in Dose Arm 2, to Day 11, Day 15, Day 22, Day 36, Day 
50 and Day 64 in Dose Arm 3 and to Day 4, Day 8, Day 15, Day 29, Day 43 and Day 57 in 
Dose Arms 4 and 5

ITP-specific autoantibodies in serum 
 over time, 
measured at Day 1, Day 36 and Day 85 in Dose Arm 1, at Day 1, Day 22 and Day 71 in Dose 
Arm 2, at Day 1, Day 15, and Day 64 in Dose Arm 3 and at Day 1, Day 8 and Day 57 in 
Dose Arms 4 and 5

Change from Baseline in IgG subclass concentrations (measured by ACM Global Central 
Laboratory) to each visit in the Dosing Period and in the Observation Period up to Day 85 in 
Dose Arm 1 and up to Day 71 in Dose Arm 2, up to Day 64 in Dose Arm 3 and up to Day 57 
in Dose Arms 4 and 5
Change #10
Other immunological variables (Section 2.2.4)

Change from Baseline in serum immunoglobulin concentrations (total IgA, IgE, and IgM) to 
the last visit in the Dosing Period and to Day 36 and Day 71 in the Observation Period in the 
4mg/kg dose arm, and to Day 22 and Day 57 in the Observation Period in the 7mg/kg dose 
arm

Change from Baseline in B- and T-lymphocyte concentrations to each visit in the Dosing 
Period and in the Observation Period up to Day 85 in the 4mg/kg dose arm and up to Day 71 
in the 7mg/kg dose arm

Change from Baseline in serum (C3 and C4) and plasma (C3a and C5a) complement levels 
to Day 15 (Dosing Period) and to Day 32 and Day 57 in the Observation Period in the 
4mg/kg dose arm, and to Day 15 (Dosing Period) and to Day 18 and Day 43 in the 
Observation Period in the 7mg/kg dose arm

Change from Baseline in serum biomarkers 
to each visit in the Dosing Period and to Day 32, Day 36, Day 43, 
Day 50, Day 57, Day 64 and Day 71 in the Observation Period in the 4mg/kg dose arm, and 
to Day 18, Day 22, Day 29, Day 36, Day 43, Day 50 and Day 57 in the Observation Period in 
the 7mg/kg dose arm

Change from Baseline in serum biomarkers 
 to each visit in the Dosing Period in both the 4mg/kg dose arm and the 
7mg/kg dose arm

Value and change from Baseline in ADA relative mass units (RMU) to each visit in the 
Dosing Period and to Day 32, Day 36, Day 43, Day 57, Day 71 and Day 85 in the 
Observation Period in the 4mg/kg dose arm, and to Day 18, Day 22, Day 29, Day 43, Day 57 
and Day 71 in the Observation Period in the 7mg/kg dose arm

Anti-drug antibody screening status (positive/negative) at each of the visits described above. 
For ADA screening positive results the confirmatory ADA result will be reported as either 
confirmed positive (CP) or not confirmed positive (NCP)
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 82 of 128

Change from Baseline in cytokines over time. Cytokines will be measured at all visits in both 
dose arms for subjects who experience infusion reactions only

Change from Baseline in serum B cell activating factor (BAFF) levels to each dosing visit in 
the Dosing Period and to Day 43 and Day 71 in the Observation Period in the 4mg/kg dose 
arm, and to Day 29 and Day 57 in the Observation Period in the 7mg/kg dose arm
Has been changed to:

Change from Baseline in serum immunoglobulin concentrations (total IgA, IgE, and IgM) to 
the last visit in the Dosing Period and to Day 36 and Day 71 in the Observation Period in 
Dose Arm 1, to Day 22 and Day 57 in the Observation Period in Dose Arm 2, to Day 15 and 
Day 50 in the Observation Period in Dose Arm 3 and to Day 8 and Day 43 in the Observation 
Period in Dose Arms 4 and 5

Change from Baseline in serum (C3 and C4) and plasma (C3a and C5a) complement levels 
to Day 15 (Dosing Period) and to Day 32 and Day 57 in the Observation Period in Dose 
Arm 1, to Day 15 (Dosing Period) and to Day 18 and Day 43 in the Observation Period in 
Dose Arm 2, to Day 11 and Day 36 in Observation Period in Dose Arm 3 and to Day 4 and 
Day 29 in Observation Period in Dose Arms 4 and 5

Change from Baseline in exploratory biomarkers relating to mechanism of action, disease 
activity, treatment response, and clinical outcome

Value and change from Baseline in ADA relative mass units (RMU) to each visit in the 
Dosing Period and to Day 32, Day 36, Day 43, Day 57, Day 71 and Day 85 in the 
Observation Period in Dose Arm 1, and to Day 18, Day 22, Day 29, Day 43, Day 57 and 
Day 71 in the Observation Period in Dose Arm 2, to Day 11, Day 15, Day 22, Day 36, Day 
50 and Day 64 in Dose Arm 3 and to Day 4, Day 8, Day 15, Day 29, Day 43 and Day 57 in 
Dose Arms 4 and 5

Anti-drug antibody screening status (positive/negative) at each of the visits described above. 
For ADA screening positive results the confirmatory ADA result will be reported as either 
confirmed positive (CP) or not confirmed positive (NCP)

Change from Baseline in cytokines over time. Cytokines will be measured at all visits in all
dose arms for subjects who experience infusion reactions only. Further description of the 
cytokines variables can be found in Appendix 13.4. Additional exploratory biomarkers may 
be investigated if needed using the samples already available.

Change from Baseline in serum B cell activating factor (BAFF) levels to each dosing visit in 
the Dosing Period and to Day 43 and Day 71 in the Observation Period in Dose Arm 1, to 
Day 29 and Day 57 in the Observation Period in Dose Arm 2, to Day 22 and Day 50 in the 
Observation Period in Dose Arm 3 and to Day 15 and Day 43 in the Observation Period in 
Dose Arms 4 and 5

Change from Baseline in B- and T-lymphocyte concentrations to each visit in the Dosing 
Period and in the Observation Period up to Day 85 in Dose Arm 1, up to Day 71 in Dose 
Arm 2, up to Day 64 in Dose Arm 3 and up to Day 57 in Dose Arms 4 and 5
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 83 of 128
Change #11
Other immunological variables (Section 2.2.4)
One item has been re-ordered to align with the order in the protocol.
Change #12
Other immunological variables (Section 2.2.4)
The following paragraph has been removed since it is already mentioned within the section:
Cytokine samples will be taken at Baseline for all subjects and at subsequent visits only if the 
subject experiences infusion reactions.
Change #13
Study design and conduct (Section 2.3)
This is a Phase 2, multicenter, open-label, multiple-dose 2-dose-arm study to evaluate the safety, 
tolerability, and efficacy of UCB7665 in subjects with primary persistent or chronic ITP. The 2 
dose arms will be as follows:

Dose Arm 1: UCB7665 4mg/kg sc (5 doses at an interval of 1 week)

Dose Arm 2: UCB7665 7mg/kg sc (3 doses at an interval of 1 week)
The maximum duration of the study per subject is approximately 16 weeks, consisting of a 
Screening Period (1 to 28 days), a Dosing Period of 2 or 4 weeks, and an Observation Period of 8 
weeks.
A data monitoring committee (DMC) will monitor emergent safety data during the study. The 
first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in Dose Arm 1 will 
not be randomized. While recruitment is still ongoing safety data for the first 3 subjects up to 7 
days after the final dose of the third subject will be reviewed by the DMC. 
During a second DMC meeting, all available safety data up to the cut off date defined as 7 days 
after the final dose of the sixth subject will be reviewed. During these reviews recruitment in the 
dose arm will not be stopped. Following this review, the DMC will make a decision on whether 
to open Dose Arm 2 for enrollment. Once the DMC has approved the opening of Dose Arm 2 for 
enrollment, subjects will subsequently be randomized to 1 of the 2 dose arms using interactive 
voice/web response system (IXRS). If the new dose arm will be initiated and if the UCB7665 
4mg/kg will be continued, new subjects will be randomized to 1 of the 2 dose arms in an 
allocation ratio of 1:1 (once 15 subjects are in the 4mg/kg group, the remaining subjects will not 
be randomized; these subjects will be allocated to the 7mg/kg group).
At least 4 interim analyses will be performed. Based on the interim analysis the DMC will assess 
the safety of UCB7665, determine whether to initiate the UCB7665 7mg/kg dose arm and may 
decide to adapt the dose regimen.
The analyses and TFLs required for the interim analyses are described in a separate interim SAP.
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 84 of 128
Has been changed to:
This is a Phase 2, multicenter, open-label, multiple-dose, multiple-arm study to evaluate the 
safety, tolerability, and efficacy of UCB7665 in subjects with primary persistent or chronic ITP. 
The 5 dose arms will be as follows:

Dose Arm 1 (15 subjects): UCB7665 4mg/kg sc (5 doses at an interval of 1 week)

Dose Arm 2 (15 subjects): UCB7665 7mg/kg sc (3 doses at an interval of 1 week)

Dose Arm 3 (6 to 12 subjects): UCB7665 10mg/kg sc (2 doses at intervals of 1 week)

Dose Arm 4 (6 to 12 subjects): UCB7665 15mg/kg sc (1 dose)

Dose Arm 5 (6 to 12 subjects): UCB7665 20mg/kg sc (1 dose)
The maximum duration of the study per subject is approximately 16 weeks, consisting of a 
Screening Period (1 to 28 days), a Dosing Period of 1 to 4 weeks, and an Observation Period of 8 
weeks.
A data monitoring committee (DMC) will monitor emergent safety data during the study. The 
first 6 subjects in the study will receive UCB7665 4mg/kg. These subjects in Dose Arm 1 will 
not be randomized. While recruitment is still ongoing safety data for the first 3 subjects up to 7 
days after the final dose of the third subject in Dose Arm 1 will be reviewed by the DMC. 
During a second DMC meeting, all available safety data up to the cut off date defined as 7 days 
after the final dose of the sixth subject in Dose Arm 1 will be reviewed. During these reviews 
recruitment in the dose arm will not be stopped. Following this review, the DMC will make a 
decision on whether to open Dose Arm 2 for enrollment. Once the DMC has advocated the 
initiation of Dose Arm 2, the subsequent subjects will be randomly assigned in 1:1 ratio to either 
Dose Arm 1 or Dose Arm 2 using an interactive voice/web response system (IXRS). Once 15 
subjects are enrolled in Dose Arm 1, the remaining subjects will enrolled in Dose Arm 2.
After the safety data review of at least 6 subjects in Dose Arm 2 is done, the DMC will make a 
recommendation on whether to open Dose Arm 3 for enrollment. Once the DMC has advocated 
the initiation of Dose Arm 3 and the enrollment of 15 subjects in Dose Arm 2 has been 
completed, the subsequent subjects will be assigned to Dose Arm 3 only. After every third 
subject has been enrolled, the DMC will review all available safety data up to cut off date 
defined as 7 days after the dosing. Depending on the emerging safety data of 6 subjects in Dose 
Arm 3, the DMC will recommend whether to open Dose Arm 4 for enrollment or to include 
additional subjects in Dose Arm 3. A maximum of 12 subjects may be enrolled in Dose Arm 3.
Once the DMC has advocated the initiation of Dose Arm 4, the enrollment of Dose Arm 3 will 
be closed and all subsequent subjects will be assigned to Dose Arm 4. After every third subject is 
enrolled, the DMC will review all available safety data up to the cutoff date defined as 7 days 
after the dosing. Depending on the emerging safety data of 6 subjects in Dose Arm 4, the DMC 
will recommend to include additional subjects in Dose Arm 4 or not. A maximum of 12 subjects 
may be enrolled in Dose Arm 4. The DMC will recommend to open Dose Arm 5 for enrollment 
in a subsequent meeting, if applicable. 
Once the DMC has advocated the initiation of Dose Arm 5, the enrollment of Dose Arm 4 will 
be closed and all subsequent subjects will be assigned to Dose Arm 5. After every third subject is 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 85 of 128
enrolled, the DMC will review all available safety data up to the cutoff date defined as 7 days 
after the dosing. Depending on the emerging safety data of 6 subjects in Dose Arm 5, the DMC 
will recommend to include additional subjects in Dose Arm 5. A maximum of 12 subjects may 
be enrolled in Dose Arm 5.
At least 11 interim analyses will be performed. Based on the interim analyses the DMC will 
assess the safety of UCB7665, determine whether to initiate subsequent dose arms and may 
decide to adapt the dose regimen. The analyses and TFLs required for the interim analyses are 
described in a separate interim SAP.
During this study, subjects will also have the option of providing additional informed consent for 
exploratory DNA and RNA analyses. Participation in this additional portion of the study is 
optional and does not preclude subject’s eligibility for participation in the main study. The 
additional genomic samples must not be collected if the subject has not consented to participate 
in this exploratory genomic substudy. Any results from this analysis will be reported separately 
and will not form a part of the main CSR. Thus, these analyses are not described further in this 
SAP.
During this study, subjects from Bulgaria, Georgia and Moldova who are enrolled in Dose Arm 
3, 4 or 5, will also have the option of providing additional informed consent for a PK/PD 
substudy (early blood sampling) at selected study sites. Participation in this additional portion of 
the study is optional and does not preclude subject’s eligibility for participation in the main 
study. The additional PK/PD blood samples must not be collected if the subject has not 
consented to participate in this exploratory substudy.
Change #14
Determination of sample size (Section 2.4, first paragraph)
The sample size of 15 subjects, in each dose arm, is mainly based on the efficacy objective of the 
study. In addition, the inclusion of 15 subjects in each dose arm will ensure that sufficient data 
are available to form conclusions about the safety of administering UCB7665.
Has been changed to:
The sample size of 15 subjects in Dose Arms 1 and 2, is mainly based on the efficacy objective 
of the study. In addition, the inclusion of 15 subjects in Dose Arms 1 and 2 will ensure that 
sufficient data are available to form conclusions about the safety of administering UCB7665. 
Based on the safety data from Dose Arms 1 and 2, the sample size of 6 to 12 subjects in Dose 
Arms 3, 4 and 5 were judged to be sufficient in order to explore subjects’ safety and IgG 
reductions under different dose regimens and is not based on a formal sample size calculation
Change #15
General presentation of summaries and analyses (Section 3.1, last paragraph)
In the event that the number of infusions in the planned dose arms (3x7mg/kg and 5x4mg/kg) are 
modified following review by the DMC, the data will be summarized based on the actual dose 
arms completing the study. For example, if the 5x4mg/kg dose arm is modified such that some 
subjects receive only 4 infusions, then the data will be summarized separately for this new dose 
regimen.
In the TFLs the dose arms will be displayed as follows where applicable:
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 86 of 128

UCB7665 5x4mg/kg

UCB7665 3x7mg/kg
If additional dose arms are initiated during the study these will be displayed similarly. For 
example, if the 5x4 mg/kg dose arm is modified such that some subjects receive only 4 infusions 
this dose arm will be displayed as UCB7665 4x4mg/kg in the TFLs.
Has been changed to:
In the event that the number of planned infusions in the dose arms are modified following review 
by the DMC, the data will be summarized based on the actual dose arms completing the study. 
For example, if the 5x4mg/kg QWK dose arm is modified such that some subjects receive only 4 
infusions, then the data will be summarized separately for this new dose regimen.
In the TFLs the dose arms will be displayed as follows where applicable:

UCB7665 5x4mg/kg QWK

UCB7665 3x7mg/kg QWK

UCB7665 2x10mg/kg QWK

UCB7665 1x15mg/kg

UCB7665 1x20mg/kg
If additional dose arms are initiated during the study these will be displayed similarly. For 
example, if the 5x4mg/kg QWK dose arm is modified such that some subjects receive only 4 
infusions this dose arm will be displayed as UCB7665 4x4mg/kg QWK in the TFLs.
Data listings containing all documented data and all derived data will be generated.
Change #16
Study periods (Section 3.2.1.2)

Dosing Period: Up to 4 weeks; during the Dosing Period subjects will receive weekly doses 
of IMP (5 doses of 4mg/kg in Dose Arm 1 and 3 doses of 7mg/kg in Dose Arm 2). The dose 
regimen may be adapted following review by the DMC;

Observation Period: 8 weeks; a visit will be scheduled 3 days after the final dose and weekly 
thereafter to collect safety and efficacy data.
Has been changed to:

Dosing Period: 1 to 4 weeks; during the Dosing Period subjects will receive weekly doses of 
UCB7665 (5 doses of 4mg/kg [QWK] in Dose Arm 1, 3 doses of 7mg/kg [QWK] in Dose 
Arm 2, 2 doses of 10mg/kg [QWK] in Dose Arm 3, 1 dose of 15mg/kg in Dose Arm 4 and 1 
dose of 20mg/kg in Dose Arm 5). The dose regimen may be adapted following review by the 
DMC

Observation Period: 8 weeks; a visit will be scheduled 3 days after the final dose (or only 
dose administration for Dose Arms 4 and 5) and weekly thereafter to collect safety and 
efficacy data
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 87 of 128
Change #17
Definition of Baseline values (section 3.3)
Table 14‒1: Definition of Baseline
Measurement
Definition of Baseline
Safety data:

Clinical chemistry (including proteins)

Hematology (including platelets measured 
locally)

Coagulation

Urinalysis

Vital signs

12-lead ECG

Predose Day 1 or if missing the Screening 
valuea
Efficacy variables:

Platelets (measured by ACM Global 
Central Laboratory)

ITP bleeding scale

NFI-MS

Platelets: Predose Day 1 or if missing the 
Screening value

ITP bleeding scale: Predose Day 1 or if 
missing the Screening assessment

NFI-MS: Predose Day 1
Pharmacodynamic variables:

Total IgG

IgG subclasses

Total IgG: Predose Day 1 or if missing the 
Screening value

IgG subclasses: Predose Day 1 or if 
missing the Screening value

ITP-specific autoantibodies: Predose Day 1
Immunological variables:

Immunoglobulins (IgA, IgE and IgM)

B- and T-lymphocytes

Serum (C3 and C4) and plasma 
complement (C3a and C5a)

ADA

Serum biomarkers 

Serum BAFF

Cytokines

Predose Day 1 (except B- and T-
lymphocytes)

B- and T-lymphocytes: Predose Day 1 or if 
missing the Screening value
ADA=anti-drug antibody; BAFF= B cell activating factor; ECG=electrocardiogram; Ig=immunoglobulin; 
ITP=primary immune thrombocytopenia; NFI-MS= Neurological Fatigue Index for Multiple Sclerosis;
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 88 of 128
Has been changed to:
Table 14‒1: Definition of Baseline
Measurement
Definition of Baseline
Safety data:

Clinical chemistry (including proteins)

Hematology (including platelets measured 
locally)

Coagulation

Urinalysis

Vital signs

12-lead ECG

Serum safety biomarkers 

Predose Day 1 or if missing the Screening 
valuea
Efficacy variables:

Platelets (measured by ACM Global 
Central Laboratory)

ITP bleeding scale

NFI-MS

Platelets: Predose Day 1 or if missing the 
Screening value

ITP bleeding scale: Predose Day 1 or if 
missing the Screening assessment

NFI-MS: Predose Day 1
Pharmacodynamic variables:

Total IgG

IgG subclasses


ITP-specific autoantibodies in serum 

Total IgG: Predose Day 1 or if missing the 
Screening value

IgG subclasses: Predose Day 1 or if 
missing the Screening value


ITP-specific autoantibodies: Predose Day 1
Immunological variables:

Immunoglobulins (IgA, IgE and IgM)

B- and T-lymphocytes

Serum (C3 and C4) and plasma 
complement (C3a and C5a)

ADA

Serum BAFF

Cytokines, if applicable (as outlined in the 
protocol)

Predose Day 1 (except B- and T-
lymphocytes)

B- and T-lymphocytes: Predose Day 1 or if 
missing the Screening value
ADA=anti-drug antibody; BAFF= B cell activating factor; ECG=electrocardiogram; Ig=immunoglobulin; 
ITP=primary immune thrombocytopenia; NFI-MS= Neurological Fatigue Index for Multiple Sclerosis;
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 89 of 128
Change #18
Full Analysis Set (Section 3.5.3)
The analysis of the PD (excluding total IgG, IgG subclasses and IgG depletion assay), efficacy 
and immunologic variables will be performed on the FAS. Efficacy analyses will be repeated for 
the PPS where stated in the SAP.
Has been changed to:
The analysis of the PD (excluding total IgG, IgG subclasses and IgG depletion assay), efficacy 
and immunologic variables will be performed on the FAS. Efficacy analyses will be repeated for 
the pharmacodynamics per protocol set (PD-PPS) where stated in the SAP.
Change #19
Pharmacodynamic Per Protocol Set (section 3.5.6)
The Pharmacodynamic Per Protocol Set (PD-PPS) is a subset of the FAS, consisting of those 
subjects who had no important protocol deviations potentially affecting the serum concentration 
of total IgG, as confirmed during a pre-analysis review of the data prior to database lock. 
The PD-PPS will be used for the analysis of the total IgG, IgG subclasses and IgG depletion 
assay.
Has been changed to:
The Pharmacodynamic Per Protocol Set (PD-PPS) is a subset of the FAS, consisting of those 
subjects who had no important protocol deviations potentially affecting the serum concentration 
of total IgG, as confirmed during a pre-analysis review of the data prior to database lock. 
Protocol deviations may not necessarily lead to total exclusion of a subject from the PD-PPS but 
may lead to exclusion of specific data.
The PD-PPS will be used for the analysis of the total IgG, IgG subclasses and IgG depletion 
assay.
Change #20
Treatment assignment and treatment groups (Section 3.6)
Treatment (dose arm) assignment for the SS, FAS, PK-PPS, PD-PPS and the PPS will be 
according to the actual treatment regimen received.
In the event that the number of infusions in the planned dose arms (3x7mg/kg and 5x4mg/kg) are 
modified following review by the DMC, the data will be summarized based on the actual dose 
arms completing the study. For example, if the 5x4mg/kg dose arm is modified such that some 
subjects receive only 4 infusions, then the data will be summarized separately for this new dose 
regimen.
Has been changed to:
Treatment (dose arm) assignment for the SS, FAS, PK-PPS, PD-PPS and the PPS will be 
according to the actual planned treatment regimen (reflecting the potential DMC decisions).
In the event that the number of planned infusions in the dose arms are modified following review 
by the DMC, the data will be summarized based on the actual dose arms completing the study.
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 90 of 128
For example, if the weekly 5x4mg/kg QWK dose arm is modified such that some subjects 
receive only 4 infusions, then the data will be summarized separately for this new dose regimen.
Change #21
Changes to protocol-defined analyses (Section 3.9)
All text was deleted with the exception of the final paragraph.
Change #22
Pharmacodynamic data (section 4.2.3)
Measurements BLQ are not anticipated in the PD data (total IgG [measured by ACM Global 
Central Laboratory, IgG subclasses and total IgG [via IgG depletion assay from LGC]). In the 
event that any BLQ measurements are received, these will be discussed at the DEM.
Has been changed to:
Measurements BLQ are not anticipated in the PD data (total IgG [measured by ACM Global 
Central Laboratory] and IgG subclasses). In the event that any BLQ measurements are received, 
these will be discussed at the DEM.
Change #23
Dates and times (Section 4.2.7)
Partial dates may be imputed for the following reasons:

Classification of AEs as treatment-emergent

Classification of medications as prior or concomitant
Has been changed to:
Partial dates may be imputed for the following reasons:

Classification of AEs as treatment-emergent

Classification of medications as past, prior or concomitant
Change #24
Handling of repeat and unscheduled measurements
All repeated and unscheduled measurements will be presented in the listings, where applicable. 
The following general rules will apply to all repeated and unscheduled measurements:

For repeated measurements obtained prior to the first dose of UCB7665 the latest value 
(which may be scheduled or unscheduled) will be used in the calculation of descriptive 
statistics;

For repeated measurements obtained at the designated Baseline visit, the latest value (which 
may be scheduled or unscheduled) will be defined as the Baseline provided that this occurred 
prior to the first dose of UCB7665;

For repeated measurements obtained at any timepoint after the first dose of UCB7665, the 
first value of any repeated measurements will be used in the calculation of changes from 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 91 of 128
Baseline and for the descriptive statistics. Unscheduled and repeated measurements will not 
be included in the descriptive statistics at timepoints after the first dose of UCB7665.
The above rules are not applicable for the determination of the response variables for the platelet 
measurements; both scheduled and unscheduled measurements may be used in the calculation of 
response, time to response and duration of response (Section 8.1.1).
Has been changed to:
All repeated and unscheduled measurements will be presented in the listings, where applicable. 
The following general rules will apply to all repeated and unscheduled measurements:

For repeated and unscheduled measurements obtained prior to the first dose of UCB7665 the 
latest value (which may be scheduled or unscheduled) will be used in the calculation of 
descriptive statistics;

For repeated and unscheduled measurements obtained at the designated Baseline visit, the 
latest value (which may be scheduled or unscheduled) will be defined as the Baseline 
provided that this occurred prior to the first dose of UCB7665;

For repeated measurements obtained at any timepoint after the first dose of UCB7665, the 
first value of any repeated measurements will be used in the calculation of changes from 
Baseline and for the descriptive statistics. Unscheduled and repeated measurements will not 
be included in the descriptive statistics at timepoints after the first dose of UCB7665, 
however they may be included in any summaries for abnormal measurements.
The above rules are not applicable for the determination of the response variables for the platelet 
measurements; both scheduled and unscheduled measurements may be used in the calculation of 
response, time to response and duration of response (Section 8.1.1).
Change #25
Interim analyses and data monitoring (Section 4.4)
For the sequential adaptive design in this study, at least 4 interim analyses will be performed. 
Safety data from the interim analyses will be reviewed by the DMC to monitor the safety, to 
adapt the dose regimen, and to decide when and if the UCB7665 7mg/kg dose arm should be 
opened.
Has been changed to:
For the sequential adaptive design in this study, at least 11 interim analyses will be performed. 
Safety data from the interim analyses will be reviewed by the DMC to monitor the safety, to 
adapt the dose regimen, and to decide when and if the UCB7665 7mg/kg weekly group (Dose 
Arm 2), UCB7665 10mg/kg weekly group (Dose Arm 3), UCB7665 15mg/kg group (Dose Arm 
4) and UCB7665 20mg/kg group (Dose Arm 5) should be opened. . 
Change #26
Examination of subgroups (Section 4.8)
The following subgroups will be defined within each dose arm:

Use of corticosteroid medication: Present
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 92 of 128

Use of corticosteroid medication: Absent
Only medication classified as either ‘prior and concomitant’ or ‘concomitant’ will be considered. 
Past use of corticosteroids (not ongoing after dosing) will not be considered for this 
classification. The list of applicable Anatomical Therapeutic Chemical (ATC) codes in order to 
identify the presence/absence of corticosteroids is provided in Section 13.1.
The descriptive summaries for platelets and total IgG will be presented for the subgroups above. 
Subgroup analyses will only be presented if the number of subjects in each subgroup is greater 
than or equal to 5 (n≥5) in each stratum.
Has been changed to:
The following subgroups will be defined within each dose arm:

Use of corticosteroid medication: Present

Use of corticosteroid medication: Absent

Responder at the end of previous ITP treatment: No

Responder at the end of previous ITP treatment: Yes
Only medication classified as either ‘prior and concomitant’ or ‘concomitant’ will be considered. 
Past use of corticosteroids (not ongoing after dosing) will not be considered for this 
classification. The list of applicable Anatomical Therapeutic Chemical (ATC) codes in order to 
identify the presence/absence of corticosteroids is provided in Section 13.1.
The descriptive summaries for platelets and total IgG will be presented for the subgroups above. 
Change #27
Subject disposition (Section 5.1, second paragraph)
The listing of subject disposition will include the date of informed consent, date of 
randomization (if applicable), date and time of first and last dose of UCB7665, date of premature 
termination and primary reason (if applicable) and date of final contact. 
The listing of study discontinuation will include the reason for discontinuation and the number of 
days on UCB7665.
The number of days on IMP will be calculated as follows:
Number of days on IMP= [(Date of Last Dose Received) – (Date of First Dose Received)] + 1
Has been changed to:
The listing of subject disposition will include the date of informed consent, date of genomic 
consent (if applicable), date of randomization (if applicable), date and time of first and last dose 
of UCB7665 (if applicable), date of premature termination and primary reason (if applicable) and 
date of final contact. 
The listing of study discontinuation will include the reason for discontinuation and the number of 
days on UCB7665.
The number of days on UCB7665 will be calculated as follows:
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 93 of 128
Number of days on UCB7665= [(Date of Last Dose Received) – (Date of First Dose Received)] 
+ 1
Change #28
Other Baseline characteristics (Section 6.2, 4th bullet point)

ITP-specific autoantibodies 
 expressed in terms of optical 
density (OD)
Has been changed to:

ITP-specific autoantibodies 
 expressed in terms of optical 
density (OD) for MAIPA analysis and pre-chloroquine minus post chloroquine treated scores 
for PIFT
Change #29
Efficacy analyses (Section 8)
The following sentence has been added at the end of this section:
Treatment (dose arm) assignment for efficacy analysis will be according to the actual treatment 
regimen.
Change #30
Platelets (Section 8.1)
The following sentence has been added at the end of this section:
In case rescue medications were taken, only the platelet data up to the time point where the 
rescue medication was taken will be utilized.
Change #31
Definition of variables (Section 8.1.1, 13th bullet)

Baseline-corrected AUEC for platelet count calculated from Baseline to the end of study visit 
(Day 85 in the Observation Period in the 4mg/kg dose arm and Day 71 in the Observation 
Period in the 7mg/kg dose arm)
Has been changed to:

Baseline-corrected AUEC for platelet count calculated from Baseline to the end of study visit 
for each of the defined dose arms.
Change #32
Definition of variables (Section 8.1.1, last bullet)

The Baseline-corrected AUEC will be calculated according to the following rules:

The AUEC will be calculated according to the linear trapezoidal rule using protocol 
scheduled visits

Unscheduled visits will not be included in the calculation
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 94 of 128

No imputation of any missing data will be performed

To account for differences in the timing of Baseline samples for each subject the Baseline 
measurement will be considered as time zero in the calculation

The units of the AUEC will be 109/L*day

The measurements at Baseline and at the last visit must be available

A minimum of 10 out of 14 measurements must be available for the calculation in the 
5x4mg/kg dose arm; a minimum of 8 out of 12 measurements must be available for the 
calculation in the 3x7mg/kg dose arm. These include the Baseline and measurement at 
the last visit

The AUEC will not be calculated in the case of early withdrawal from the study
Has been changed to:

The Baseline-corrected AUEC will be calculated according to the following rules:

The AUEC will be calculated according to the linear trapezoidal rule using protocol 
scheduled visits

Unscheduled visits will not be included in the calculation

No imputation of any missing data will be performed

To account for differences in the timing of Baseline samples for each subject the Baseline 
measurement will be considered as time zero in the calculation

The units of the AUEC will be 109/L*day

The measurements at Baseline and at the last visit must be available

A minimum of 10 out of 14 measurements must be available for the calculation in Dose 
Arm 1; a minimum of 8 out of 12 measurements must be available for the calculation in 
Dose Arm 2; a minimum of 7 out of 11 must be available for the calculation in Dose Arm 
3; a minimum of 5 out of 9 must be available for the calculation in Dose Arms 4 and 5. 
These include the Baseline and measurement at the last visit

The AUEC will not be calculated in the case of early withdrawal from the study
Change #33
Presentation of results (Section 8.1.2)
Individual platelet and total IgG (including IgG subclasses, measured by ACM Global Central 
Laboratory) concentrations will be displayed graphically over time (Day 1 to Day 85 for the 
4mg/kg dose arm and Day 1 to Day 71 for the 7mg/kg dose arm) for each subject (linear scale). 
The platelet and total IgG concentrations will be overlaid on the same plot (discrete y-axes) with 
separate plots for each subject (2 lines per plot). Additional plots will be presented with the 
platelet and IgG subclasses overlaid on the same figure (5 lines per plot). All plots will include a 
vertical reference line to indicate when the last dose was administered for each subject.
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 95 of 128
Has been changed to:
Individual platelet and total IgG (including IgG subclasses, measured by ACM Global Central 
Laboratory) concentrations will be displayed graphically over time (Day 1 to Day 85 for Dose 
Arm 1; Day 1 to Day 71 for Dose Arm 2; Day 1 to Day 64 for Dose Arm 3 and Day 1 to Day 57 
for Dose Arms 4 and 5) for each subject (linear scale). The platelet and total IgG concentrations 
will be overlaid on the same plot (discrete y-axes) with separate plots for each subject (2 lines 
per plot). Additional plots will be presented with the platelet and IgG subclasses overlaid on the 
same figure (5 lines per plot). All plots will include a vertical reference line to indicate when the 
last dose was administered for each subject.
Change #34
Analysis of time to responder (Section 8.1.3.2)
The point estimate for the median number of days to response with 95% CIs will be given if 
estimable. Further a summary including the number and percent of censored subjects, the 
number of responders and total subjects by dose arm and in total will be given.
Has been changed to:
The point estimate for the median number of days to response with 90% CIs will be given if 
estimable. Further a summary including the number and percent of censored subjects, the 
number of responders and total subjects by dose arm and in total will be given.
Change #35
Pharmacokinetics (Section 9.1)
The following paragraphs have been added at the end of this section:
The above summaries will be repeated separately for the subjects in the PK/PD substudy sample, 
in the event of very few subjects (<10 subjects) only listings will be provided.
Further analyses and summaries relating to the population PK analyses and PK/PD analyses will 
described in a separate SAP and reported separately.
Change #36
Pharmacodynamics (Section 9.2)
The following paragraph has been added at the end of this section:
The above summaries will be repeated separately for the subjects in the PK/PD substudy sample, 
in the event of very few subjects (<5 subjects) only listings will be provided.
Change #37
ITP-specific autoantibodies (Section 9.2.1)
In order to evaluate the relationship between changes in platelet count and total IgG, IgG 
subclasses and ITP-specific autoantibodies the following figures will be presented:

Individual ITP-specific autoantibodies and platelet counts (measured by ACM Global Central 
Laboratory) will be displayed graphically over time (Day 1 to Day 85 for the 4mg/kg dose 
REDACTED COPY 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 96 of 128
arm and Day 1 to Day 71 for the 7mg/kg dose arm) for each subject (linear scale). The 
ITP-specific autoantibodies 
 and platelet counts will be 
overlaid on the same plot (discrete y-axes) with separate plots for each subject (4 lines per 
plot) 

A scatter plot of platelet counts (measured by ACM Global Central Laboratory) versus 
ITP-specific autoantibodies measured at the same timepoint will be presented in linear scale, 
with separate plots for each dose arm and for each variable 
 All subjects and timepoints will be included on the same plot for each dose arm

Individual ITP-specific autoantibodies and total IgG (from ACM Global Central Laboratory) 
will be displayed graphically over time (Day 1 to Day 85 for the 4mg/kg dose arm and Day 1 
to Day 71 for the 7mg/kg dose arm) for each subject (linear scale). The ITP-specific 
autoantibodies 
 and total IgG will be overlaid on the same 
plot (discrete y-axes) with separate plots for each subject (4 lines per plot). These plots will 
be repeated for each of the IgG subclasses.
Has been changed to:
In order to evaluate the relationship between changes in platelet count and total IgG, IgG 
subclasses and ITP-specific autoantibodies the following figures will be presented:

Individual ITP-specific autoantibodies and platelet counts (measured by ACM Global Central
Laboratory) will be displayed graphically over time (Day 1 to Day 85 for Dose Arm 1; Day 1 
to Day 71 for Dose Arm 2; Day 1 to Day 64 for Dose Arm 3 and Day 1 to Day 57 for Dose 
Arms 4 and 5) for each subject (linear scale). The ITP-specific autoantibodies 
and platelet counts will be overlaid on the same plot (discrete y-
axes) with separate plots for each subject (4 lines per plot) 

A scatter plot of platelet counts (measured by ACM Global Central Laboratory) versus 
ITP-specific autoantibodies measured at the same timepoint will be presented in linear scale, 
with separate plots for each dose arm and for each variable 
. All subjects and timepoints will be included on the same plot for each dose arm

Individual ITP-specific autoantibodies and total IgG (from ACM Global Central Laboratory)
will be displayed graphically over time (Day 1 to Day 85 for Dose Arm 1; Day 1 to Day 71 
for Dose Arm 2; Day 1 to Day 64 for Dose Arm 3 and Day 1 to Day 57 for Dose Arms 4 and 
5) for each subject (linear scale). The ITP-specific autoantibodies 
and total IgG will be overlaid on the same plot (discrete y-axes) with separate plots 
for each subject (4 lines per plot). These plots will be repeated for each of the IgG subclasses.
Change #38
Serum biomarkers (
 BAFF) will 
be listed by dose arm and timepoint including changes from Baseline. Descriptive summaries 
(including n, arithmetic mean, median, SD, minimum and maximum) will be presented by dose 
arm and timepoint for both absolute values and changes from Baseline.
Has been changed to:
Serum safety biomarkers 
 and BAFF will be listed by dose arm and timepoint including changes 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 97 of 128
from Baseline. Descriptive summaries (including n, arithmetic mean, median, SD, minimum and 
maximum) will be presented by dose arm and timepoint for both absolute values and changes 
from Baseline.
Change #39Anti-drug antibodies (Section 9.3.4)
Full section has been updated with the following text:
Immunological variables will be analyzed for all subjects in the SS. Anti-UCB7665 antibody 
data will be summarized at each scheduled visit, and the rate of ADA positive subjects will be 
calculated.
A calibrator screening assay measures ADA as relative mass units (RMU) in units/mL. A cut 
point will be determined by the bioanalytical laboratory that will be used to determine the status 
of ADA as above the cut point (ACP) or below the cut point (BCP). The RMU result from the 
calibrator screening assay will be used to report ADA levels.
For any ADA levels that are ACP, a further confirmatory assay will be performed, the results of 
which will be determined as either ‘confirmed positive’ (CP) or ‘not confirmed positive’ (NCP). 
The results for the ADA measurements will be listed by treatment group and time point based on 
the SS, including the screening assay, confirmatory assay and level in units/mL. 
The following definitions will be applied:

An ADA status of positive will be concluded for any subject with an ADA level that is ACP 
and CP at any time point 

An ADA status of negative will be concluded for any subject with an ADA level that is either 
BCP or ACP and NCP at any time point

A subject will be classified as having ADA positivity at Baseline if the Day 1, predose result 
is ACP and CP

A subject will be classified as having treatment-emergent ADA positivity when meeting one 
of the following criteria:

The Baseline result is either BCP or ACP and NCP, and at least one post-Baseline time 
point is ACP and CP

The Baseline result is positive (ACP and CP) and at least one post-Baseline measurement 
shows a pre-defined fold increase in units/mL from the Baseline value (the fold increase 
from Baseline required to meet this criteria will be defined with the development of the 
assay and will be included in the TFLs)

A subject will be classified as overall positive if at least one post-Baseline measurement is 
ACP and CP (this includes subject who have negative results at Baseline)

A subject will be classified as overall negative if at all post-Baseline visits the ADA status is 
negative (this includes subjects who have positive [ACP and CP] results at Baseline)

Inconclusive: pre-ADA negative or pre-ADA positive subjects with negative ADA samples 
post baseline for which time matched drug levels are above the demonstrated drug tolerance 
characteristics of the ADA screening assay at one or more sampling time points
REDACTED COPY 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 98 of 128

Missing: relevant samples are missing
The ADA status (positive/negative) will be summarized as a categorical endpoint (number and 
percentage of subjects) for all time points and overall, based on the SS. 
In addition, the first occurrence of treatment-emergent ADA positivity (based on the definitions 
above) will be summarized (number and percentage of subjects) at each post-Baseline visit, 
based on the SS. This tabulation will count the number of subjects at each post-Baseline visit 
who fulfill at least one of the above defined criteria for treatment-emergent positivity; subjects 
will be counted in the numerator based on the earliest visit at which one of these criteria is 
fulfilled. At other visits, subjects will be counted in the denominator (assuming a measurement is 
available). For all tabulations, percentages will be based on the number of observations at each 
visit.
A separate listing will be presented (based on the SS) showing the UCB7665 concentrations and 
ADA measurements in the same output in adjacent columns. The listing will include the 
UCB7665 concentration, ADA status (ACP or BCP) and confirmatory assay results if applicable 
(NCP or CP), together with the units/mL for results that are CP. In addition the time since the 
previous administration of IMP will be reported (in days).
Finally, individual subject plots (based on the SS) will be presented displaying the ADA 
units/mL and UCB7665 concentrations overlaid on the same figure. The figure will also show 
the timing and dose of each administration of UCB7665 received during the study.
The rules for handling values that are BLQ in the UCB7665 concentration data are described in 
Section 4.2.5 For the ADA data, any negative results for which there are no units/mL available at 
a specific visit will be substituted with 0.001 for the purpose of the figure.
Change #40
Extent of exposure (Section 10.1)
The planned dose regimens are as follows:

Subjects in Dose Arm 1 will receive 5 sc doses of UCB7665 4mg/kg at 1-week intervals

Subjects in Dose Arm 2 will receive 3 sc doses of UCB7665 7mg/kg at 1-week intervals
Has been changed to:
The planned dose regimens are as follows:

Subjects in Dose Arm 1 will receive 5 sc doses of UCB7665 4mg/kg at 1-week intervals

Subjects in Dose Arm 2 will receive 3 sc doses of UCB7665 7mg/kg at 1-week intervals

Subjects in Dose Arm 3 will receive 2 sc doses of UCB7665 10mg/kg at 1-week intervals

Subjects in Dose Arm 4 will receive 1 sc dose of UCB7665 15mg/kg 

Subjects in Dose Arm 5 will receive 1 sc doses of UCB7665 20mg/kg 
REDACTED COPY
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 99 of 128
Change #35
Adverse events (Section 10.2)
In addition, AEs will be classified according to the CTCAE Version 4.03 for severity. For any 
AEs where it is not possible to provide a CTCAE grading, the events will be assessed using a 
standard intensity classification (mild, moderate and severe). For the purpose of the tabulations 
all CTCAE severity classifications will be mapped to a mild/moderate/severe grade as described 
in the below sections.
Has been changed to:
In addition, AEs will be classified according to the CTCAE Version 4.03 for severity. For any 
AEs where it is not possible to provide a CTCAE grading, the events will be assessed using a 
standard intensity classification (mild, moderate and severe). For the purpose of the tabulations 
all CTCAE severity classifications will be mapped to a mild/moderate/severe grade as described 
in the below sections. Bleeding events classified as Grade 1 or Grade 2 (based on CTCAE) will 
not be reported as AEs as these will be assessed and reported as part of the ITP-BAT 
assessments. Bleeding events classified as Grade 3 or higher, based on CTCAE, will be reported 
as AEs.
Change #36
Potential drug-induced liver injury (Section 10.3.1)
Subjects who meet any of the following criteria at a given timepoint will be listed:

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) increase ≥5 x upper 
limit of normal (ULN) 

Alanine aminotransferase or AST increase ≥3 x ULN and total bilirubin ≥2 x ULN

Alanine aminotransferase or AST increase ≥3 x ULN (and ≥2 x Baseline) and <5 x ULN, 
with total bilirubin <2 x ULN

Alanine aminotransferase or AST increase ≥5 x ULN (and ≥2 x Baseline), with total bilirubin 
<2 x ULN

Alanine aminotransferase or AST increase ≥8 x ULN

Alkaline phosphatase (ALP) ≥2 x ULN
Has been changed to:
Subjects who meet any of the following criteria at a given timepoint will be listed:

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) increase ≥5 x upper 
limit of normal (ULN) 

ALT or AST increase ≥3 x ULN and total bilirubin ≥2 x ULN

ALT or AST increase ≥3 x ULN who exhibit temporally associated symptoms of hepatitis or 
hypersensitivity.

ALT or AST increase ≥3 x ULN (and ≥2 x Baseline) and <5 x ULN, with total bilirubin <2 x 
ULN
REDACTED COPY 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 100 of 128

ALT or AST increase ≥5 x ULN (and ≥2 x Baseline), with total bilirubin <2 x ULN and no 
eosinophilia (i.e., ≤5%), with no fever, rash, or symptoms of hepatitis

Alkaline phosphatase (ALP) ≥2 x ULN

Change #37
Treatment group assignment for the TFLs (Section 13.6)
Treatment Label
TFL group
UCB7665 5x4mg/kg
UCB7665 3x7mg/kg
All Subjects
Subject disposition
X
X
X
Protocol deviations
X
X
X
Demographics
X
X
X
Baseline 
characteristics
X
X
Medical history
X
X
X
Prior and concomitant 
medications
X
X
X
Adverse events
X
X
X
Safety measurements 
(including safety 
laboratory tests, vital 
signs and ECG)
X
X
Efficacy (platelets, 
ITP bleeding score, 
NFI-MS)
X
X
PK
X
X
PD (ITP-specific 
autoantibodies, total 
IgG,IgG subclasses 
and IgG depletion 
assay)
X
X
Immunological 
(serum 
immunoglobulins, B-
and T-lymphocytes, 
serum and plasma 
complement, serum 
biomarkers, ADA and 
cytokines)
X
X
REDACTED COPY 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 101 of 128
Has been changed to:
Treatment Labela
TFL group
UCB7665 
5x4mg/k
g weekly
(Dose 
Arm 1)
UCB7665 
3x7mg/kg 
weekly 
(Dose 
Arm 2)
UCB7665 
2x10mg/kg 
weekly
(Dose Arm 
3)
UCB7665 
1x15mg/kg 
(Dose Arm 
4)
UCB7665 
1x20mg/kg 
(Dose Arm 
5)
All 
Subject
s
Subject disposition
X
X
X
X
X
X
Protocol deviations
X
X
X
X
X
X
Demographics
X
X
X
X
X
X
Baseline 
characteristics
X
X
X
X
X
Medical history
X
X
X
X
X
X
Prior and concomitant 
medications
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
Safety measurements 
(including safety 
laboratory tests, vital 
signs and ECG)
X
X
X
X
X
Efficacy (platelets, 
ITP bleeding score, 
NFI-MS)
X
X
X
X
X
PK
X
X
X
X
X
PD (ITP-specific 
autoantibodies, total 
IgG,IgG subclasses 
and IgG depletion 
assay)
X
X
X
X
X
Immunological (serum 
immunoglobulins, B-
and T-lymphocytes, 
serum and plasma 
complement, serum 
biomarkers, ADA and 
cytokines)
X
X
X
X
X
ACTED COPY 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 102 of 128
14.2
Amendment 2
14.2.1
Rationale for the amendment
The second SAP amended has been developed to include some requirements observed during the 
study Dry Run as well as to include the ad-hoc outputs which were not part of the initial SAP. 
Updates made in the CRF are also described here. Few other minor formatting updates were 
made.
14.2.2
List of changes
Specific changes
Change #1
General along the document
In some places, “timepoint” has been changed to “visit” to make the text more appropriate to 
how the data is collected; hence “timpoint” is now only referring to a “moment of time” within a 
visit or to a general moment during the study conduction.
Change #2
Definition of Baseline values (Section 3.3)
Baseline will be the last available predose value prior to the first infusion of UCB7665, or if 
missing, the Screening values. 
Measurement-specific Baseline timepoints (based on the planned measurements) are presented in 
Table 3‒1.
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 103 of 128
Table 14‒1: Definition of Baseline
Measurement
Definition of Baseline
Safety data:

Clinical chemistry (including proteins)

Hematology (including platelets measured 
locally)

Coagulation

Urinalysis

Vital signs

12-lead ECG

Serum safety biomarkers 

Predose Day 1 or if missing the Screening 
valuea
Efficacy variables:

Platelets (measured by ACM Global 
Central Laboratory)

ITP bleeding scale

NFI-MS

Platelets: Predose Day 1 or if missing the 
Screening value

ITP bleeding scale: Predose Day 1 or if 
missing the Screening assessment

NFI-MS: Predose Day 1
Pharmacodynamic variables:

Total IgG

IgG subclasses


ITP-specific autoantibodies in serum 

Total IgG: Predose Day 1 or if missing the 
Screening value

IgG subclasses: Predose Day 1 or if 
missing the Screening value

ITP-specific autoantibodies: Predose Day 1
Immunological variables:

Immunoglobulins (IgA, IgE and IgM)

B- and T-lymphocytes

Serum (C3 and C4) and plasma 
complement (C3a and C5a)

ADA

Serum BAFF

Cytokines, if applicable (as outlined in the 
protocol)

Predose Day 1 (except B- and T-
lymphocytes)

B- and T-lymphocytes: Predose Day 1 or if 
missing the Screening value
If the Screening value is to be used as Baseline (i.e., predose Day 1 is missing), the highest value 
for the platelet count obtained from the 2 measurements at Screening will be used as the 
Baseline.
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 104 of 128
Has been changed to:
Baseline will be the last available predose value prior to the first infusion of UCB7665, or if 
missing, the latest no missing value prior to Baseline (screening value or unscheduled visit 
value). 
Measurement-specific Baseline timepoints (based on the scheduled or unscheduled 
measurements) are presented in Table 3‒1.
Table 14‒1: Definition of Baseline
Measurement
Definition of Baseline
Safety data:

Clinical chemistry (including proteins)

Hematology (including platelets measured 
locally)

Coagulation

Urinalysis

Vital signs

12-lead ECG

Serum safety biomarkers

Predose Day 1 or if missing the latest no 
missing value prior to Day 1
Efficacy variables:

Platelets (measured by ACM Global 
Central Laboratory)

ITP bleeding scale

NFI-MS

Platelets: Predose Day 1 or if missing the 
latest no missing value prior to Day 1

ITP bleeding scale: Predose Day 1 or if 
missing the latest no missing value prior to 
Day 1

NFI-MS: Predose Day 1
Pharmacodynamic variables:

Total IgG

IgG subclasses


ITP-specific autoantibodies in serum 

Total IgG: Predose Day 1 or if missing the 
latest no missing value prior to Day 1

IgG subclasses: Predose Day 1 or if 
missing the latest no missing value prior to 
Day 1

ITP-specific autoantibodies: Predose Day 1
Immunological variables:

Immunoglobulins (IgA, IgE and IgM)

B- and T-lymphocytes

Serum (C3 and C4) and plasma 
complement (C3a and C5a)

ADA

Serum BAFF

Cytokines, if applicable (as outlined in the 
protocol)

Predose Day 1 (except B- and T-
lymphocytes)

B- and T-lymphocytes: Predose Day 1 or if 
missing the latest no missing value prior to 
Day 1
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 105 of 128
If the latest non missing value prior to Baseline is to be used as Baseline (i.e., predose Day 1 is 
missing), the highest value for the platelet count obtained from the last 2 non missing 
measurements prior to Baseline will be used as the Baseline.
Change #3
Electrocardiograma data (Section 4.2.6)
For the ECG data, all calculations of changes from Baseline and descriptive statistics will be 
based on the mean of the triplicate assessments at each timepoint. In the event that there are not 3 
available measurements at a given timepoint, the mean will be calculated based on the number of 
measurements for which data is provided.
Has been changed to:
For the ECG data, all calculations of changes from Baseline and descriptive statistics will be 
based on the mean of the triplicate assessments at each visit. In the event that there are not 3 
available measurements at a given visit, the mean will be calculated based on the number of 
measurements for which data is provided (variables analyzed will be those described in Section 
10.4.2).
Change #4
Examination of subgroups (Section 4.8)
The following subgroups will be defined within each dose arm:

Use of corticosteroid medication: Present

Use of corticosteroid medication: Absent

Responder at the end of previous ITP treatment: No

Responder at the end of previous ITP treatment: Yes
Only medication classified as either ‘prior and concomitant’ or ‘concomitant’ and medical 
procedure will be considered for ITP treatment. Responder categories will be defined taking into 
account the last valid value reported (either Yes or No) for each patient. Past use of 
corticosteroids (not ongoing after dosing) will not be considered for this classification. The list of 
applicable Anatomical Therapeutic Chemical (ATC) codes in order to identify the 
presence/absence of corticosteroids is provided in Section 13.1.
Has been changed to:
The following subgroups will be defined within each dose arm:

Use of corticosteroid medication: Present/Absent

Responder at the end of previous ITP treatment: No/Yes/Unknown

Previous intravenous immunoglobulin (IVIg) therapy: Yes/No 

Number of previous ITP therapies: ≤2/>2
Only medication classified as either ‘prior and concomitant’ or ‘concomitant’ and medical 
procedure will be considered for ITP treatment. Responder categories will be defined taking into 
account the last reported ITP treatment value (either Yes or No) for each patient. If this value is 
REDACTED COPY 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 106 of 128
unknown, the second-last reported ITP treatment value will be used, then the third-last, and so 
on, until a known response is provided. The Unknown responder category will only be 
considered in cases where the investigator has never reported a category (Yes or No) for any of 
the previous ITP treatments. Past use of corticosteroids (not ongoing after dosing) will not be 
considered for this classification. The list of applicable Anatomical Therapeutic Chemical (ATC) 
codes in order to identify the presence/absence of corticosteroids is provided in Section 13.1.
Change #5
Demographics (Section 6.1)
All Baseline demographic characteristics (with the exception of year of birth) will be 
summarized by dose arm and overall for the SS. 
Has been changed to:
All Baseline demographic characteristics (with the exception of year of birth) will be 
summarized by dose arm and overall for the SS. Number and percentage of patients with a BMI 
equal or higher than 30 will also be summarized by dose arm.
Change #6
Other Baseline characteristics (Section 6.2)
Baseline disease characteristics will be listed and summarized by dose arm for the SS including 
the following:

Duration of disease

Karnofsky Performance Scale Index

ITP bleeding scale (skin, visible mucosae and organs, with gradation of severity [SMOG])

ITP-specific autoantibodies 
 expressed in terms of optical 
density (OD) for MAIPA analysis and pre-chloroquine minus post chloroquine treated scores 
for PIFT

Immunological variables (IgG [including total IgG and IgG subclasses measured by ACM 
Global Central Laboratory], IgM, IgA, IgE and lymphocytes [B and T])

Serum (C3 and C4) and plasma complement levels (C3a and C5a)

Platelet count (measured by ACM Global Central Laboratory)
Has been changed to:
Baseline disease characteristics will be listed and summarized by dose arm for the SS including 
the following:

Duration of disease

Karnofsky Performance Scale Index

ITP bleeding scale (skin, visible mucosae and organs, with gradation of severity [SMOG])
REDACTED COPY
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 107 of 128

ITP-specific autoantibodies 
 expressed in terms of optical 
density (OD) for MAIPA analysis and pre-chloroquine minus post chloroquine treated scores 
for PIFT

Immunological variables (IgG [including total IgG and IgG subclasses measured by ACM 
Global Central Laboratory], IgM, IgA, IgE and lymphocytes [B and T])

Serum (C3 and C4) and plasma complement levels (C3a and C5a)

Platelet count (measured by ACM Global Central Laboratory)

Number of prior ITP medications received

Number of prior ITP medications received categorized

Prior ITP medications received by preferred term

Medical history of splenectomy (MedDRA v20.2, Preferred Term=”Splenectomy”)
Change #7
Measurements of treatment compliance (Section 7)
The study medication will be administered and monitored by the investigator or designee. The 
measured plasma concentrations will provide information regarding compliance. Any dosing 
deviations (eg, incomplete infusion volume administered, infusion temporarily interrupted, 
infusion discontinued) will be discussed at the DEM and any actions taken regarding the 
analyses will be documented accordingly and discussed in the CSR.
Has been changed to:
The study medication will be administered and monitored by the investigator or designee. The 
measured plasma concentrations will provide information regarding compliance. Any dosing 
deviations (eg, incomplete infusion volume administered, infusion discontinued) will be 
discussed at the DEM and any actions taken regarding the analyses will be documented 
accordingly and discussed in the CSR.
Change #8
Platelets (Section 8.1)
All efficacy analyses are based on platelet count measured by ACM Global Central Laboratory. 
Measurements of platelet count obtained by the local laboratory will be listed and summarized as 
part of the safety laboratory data. These are not included in the analyses described in the sections 
below. All tabulations and mean figures will be presented for both the FAS and the PPS unless 
otherwise stated. Individual figures will be presented for the FAS only. In case rescue 
medications are taken, only the platelet data up to the time point where the rescue medication is 
taken will be utilized.
Has been changed to:
All efficacy analyses are based on platelet count measured by ACM Global Central Laboratory. 
Measurements of platelet count obtained by the local laboratory will be listed and summarized as 
part of the safety laboratory data. These are not included in the analyses described in the sections 
below. All tabulations and mean figures will be presented for both the FAS and the PPS unless 
REDACTED COPY 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 108 of 128
otherwise stated. Median figures and individual figures will be presented for the FAS only. In 
case rescue medications are taken, only the platelet data up to the time point where the rescue 
medication is taken will be utilized for the summary tables. Listings will contain all the data but 
a footnote will be included indicating the patients for which some data has been excluded from 
the summary tables.
Change #9
Presentation of results (Section 8.1.2)
The individual platelet measurements will be listed by dose arm and timepoint including changes 
from Baseline (Day 1, predose). Descriptive summaries (including n, arithmetic mean, median, 
SD, minimum and maximum) will be presented by dose arm and scheduled timepoint for both 
absolute values and changes from Baseline. Summary tabulations by dose arm will be repeated 
for the subgroups defined in Section 4.8 (based on the FAS only).
Has been changed to:
The individual platelet measurements will be listed by dose arm and visit including changes from 
Baseline (Day 1, pre-dose). Descriptive summaries (including n, arithmetic mean, median, SD, 
minimum and maximum) will be presented by dose arm and scheduled visit for both absolute 
values and changes from Baseline based on the FAS only. Summary tabulations by dose arm will 
be repeated for the subgroups defined in Section 4.8 (based on the FAS only too).
Change #10
Presentation of results (Section 8.1.2)
Mean and mean change from Baseline platelet values will be plotted versus scheduled visit by 
dose arm with all dose arms overlaid on the same plot. Similar plots will be provided for 
response rate over time (response, complete response and platelet count ≥50x109/L). 
Individual platelet and total IgG (including IgG subclasses, measured by ACM Global Central 
Laboratory) concentrations will be displayed graphically over time (Day 1 to Day 85 for Dose 
Arm 1; Day 1 to Day 71 for Dose Arm 2; Day 1 to Day 64 for Dose Arm 3 and Day 1 to Day 57 
for Dose Arms 4 and 5) for each subject (linear scale). The platelet and total IgG concentrations 
will be overlaid on the same plot (discrete y-axes) with separate plots for each subject (2 lines 
per plot). Additional plots will be presented with the platelet and IgG subclasses overlaid on the 
same figure (5 lines per plot). All plots will include a vertical reference line to indicate when the 
last dose was administered for each subject.
Has been changed to:
Mean and mean change from Baseline platelet values will be plotted versus scheduled visit by 
dose arm with all dose arms overlaid on the same plot. Similar plots will be provided for 
response rate over time (response, complete response and platelet count ≥50x109/L). Mean 
median, mean change and median change from Baseline total IgG results will be plotted over 
time by dose arm with all dose arms overlaid on the same plot.
Individual platelet and total IgG (including IgG subclasses, measured by ACM Global Central 
Laboratory) concentrations will be displayed graphically over time (Day 1 to Day 85 for Dose 
Arm 1; Day 1 to Day 71 for Dose Arm 2; Day 1 to Day 64 for Dose Arm 3 and Day 1 to Day 57 
for Dose Arms 4 and 5) for each subject (linear scale). The platelet and total IgG concentrations 
REDACTED COPY
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 109 of 128
will be overlaid on the same plot (discrete y-axes) with separate plots for each subject (2 lines 
per plot). Additional plots will be presented with the platelet and IgG subclasses overlaid on the 
same figure (5 lines per plot). All plots will include a vertical reference line to indicate when the 
last dose was administered for each subject. The mean (and median in a separate plot) change 
from baseline in platelet and the mean (median) change from baseline in total IgG concentrations 
will be overlaid on the same plot (discrete y-axes) with separate plots for each dose arm (2 lines 
per plot).
Change #11
Analysis of responder rate (Section 8.1.3.3)
The following paragraphs have been added at the end of this subsection:
Moreover, for responder rate, summary tabulations by dose arm will be repeated according to 
previous intravenous immunoglobulin therapy (Yes/No) and the number of previous medications 
(≤2/>2). Percentage of days without bleeding will also be described by dose arm for each type of 
response (response, complete response and platelet Count >=50x10/L). Percentage of days 
without bleeding is calculated using the following formula:
((N of visits with a SMOG score – N of these visits where bleeding occurred) / N of visits with a 
SMOG score) x 100
In case rescue medications are taken, only the data up to the start date of rescue medication will 
be utilized for the summary tables. Listings will contain all the data but a footnote will be 
included indicating the patients for which some data has been excluded from the summary tables. 
In case of partial dates, the imputation rules for partial dates described in Section 4.2.7 will be 
applied.
Change #12
IPT bleeding score and platelet response (Section 8.2.1.1)
All response variables described above will be listed by dose arm and subject and summarized 
by dose arm and visit where appropriate. The responder rates will be tabulated as described in 
Section 8.1.3.3. All analyses described in this section will be performed for the FAS.
Has been changed to:
All response variables described above will be listed by dose arm and subject and summarized 
by dose arm and visit where appropriate. The responder rates will be tabulated as described in 
Section 8.1.3.3. Moreover the change in category of bleeding from Baseline will also be 
presented in shift table at all post-Baseline timepoints by dose arm. Summary tabulations for 
Clinical Response by dose arm will be repeated according to previous intravenous 
immunoglobulin therapy (Yes/No) and the number of previous medications (≤2/>2). All analyses 
described in this section will be performed for the FAS.
In case rescue medications are taken, only the data up to the start date of rescue medication will 
be utilized for the summary tables. Listings will contain all the data but a footnote will be 
included indicating the patients for which some data has been excluded from the summary tables.
In case of partial dates, the imputation rules for partial dates described in Section 4.2.7 will be 
applied.
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 110 of 128
Change #13
Pharmacokinetics (Section 9.1)
The following sentence has been removed from this section:
If applicable, a separate listing of UCB7665 concentrations in the cerebrospinal fluid (CSF) will 
be presented by dose arm. These data will not be summarized.
Change #14
ITP-specific autoantibodies (Section 9.2.1)
The results will be expressed in the form of the OD value.
ITP-specific autoantibodies (OD value ) will be listed by dose arm and timepoint. Values that are 
ALD will be displayed as such in the listings.
Has been changed to:
The results will be expressed in the form of the OD value and for indirect PIFT method using the 
following categories: 0 = negative; 0.5 = week positive; 1 = positive; 2 = positive; 3 = strong 
positive; 4 = strong positive.
ITP-specific autoantibodies (OD value and PIFT categories) will be listed by dose arm and 
timepoint. OD values that are ALD will be displayed as such in the listings.
Change #15
ITP-specific autoantibodies (Section 9.2.1)
The following sentence has been added at the end of this section:
Only patients with positive ITP-specific autoantibodies will be described.
Change #16
Total IgG and IgG subclasses (Section 9.2.2)
Mean and mean percentage change from Baseline values in total IgG (measured by ACM Global 
Central Laboratory) will be plotted over time by dose arm with all dose arms overlaid on the 
same plot. Additional figures will be presented in conjunction with the ADA results as described 
in Section 9.3.4 as well as figures in conjunction with the platelet results as described in 
Section 8.1.1.
Finally, a separate figure will be presented by subject showing the individual total IgG results 
from ACM Global Central Laboratory.
Any values that are BLQ or ALQ will be handled as described in Section 4.2.32.
All analyses described in this section will be performed on the PD-PPS. In case rescue 
medications are taken, only the IgG data up to the timepoint where the rescue medication is 
taken will be utilized for the summary tables. Listings will contain all the data but a footnote will 
be included indicating the patients for which some data has been excluded from the summary 
tables.
Has been changed to:
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 111 of 128
Mean, median, median change from Baseline and mean and median percentage change from 
Baseline values in total IgG (measured by ACM Global Central Laboratory) will be plotted over 
time by dose arm with all dose arms overlaid on the same plot. Additional figures will be 
presented in conjunction with the ADA results as described in Section 9.3.4 as well as figures in 
conjunction with the platelet results as described in Section 8.1.1.
Finally, a separate figure will be presented by subject showing the individual total IgG results 
from ACM Global Central Laboratory.
Any values that are BLQ or ALQ will be handled as described in Section 4.2.3.
All analyses described in this section will be performed on the PD-PPS. In case rescue 
medications are taken, only the IgG data up to the start date of rescue medication will be utilized 
for the summary tables. Listings will contain all the data but a footnote will be included 
indicating the patients for which some data has been excluded from the summary tables. In case 
of partial dates, the imputation rules for partial dates described in Section 4.2.7 will be applied.
Change #17
Adverse events (Section 10.2)
In addition the listing will flag AEs that led to discontinuation, TEAEs, AEs of interest, AEs of 
special interest, infusion reactions and SAEs.
Has been changed to:
In addition the listing will flag AEs that led to discontinuation, TEAEs, AEs of interest, AEs of 
special interest, infusion reactions, SAEs, Sampson criteria and CTCAE grade.
Change #18
Clinical laboratory evaluations (Section 10.3)
Values outside the reference range for the numeric variables will be flagged in the listings and in 
addition, will be listed separately. The reference ranges will also be reported in the listings.
Has been changed to:
Values outside the reference range for the numeric variables will be flagged in the listings and in 
addition, results considered as markedly abnormal laboratory results (CTCAE Grade 3 and 
above) will be listed separately. The reference ranges will also be reported in the listings.
Change #19
Vital signs (Section 10.4.1)
Table 10-2 has been updated as follows:
Variable
Unit
Low
High
Systolic blood pressure
mmHg
Value <90 and ≥20 
decrease from Baseline
Value >180 and ≥15 
increase from baseline
Diastolic blood pressure
mmHg
Value <50 and ≥15 
decrease from Baseline
Value >105 and ≥15 
increase from Baseline
Change #20
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07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
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Electrocardiograms (Section 10.4.2)
The following sentence has been added at the end of this subsection:
The number and percentage of subjects with TEMA/PCS ECG values will be summarized by 
dose arm at each timepoint.
Change #21
Electrocardiograms (Section 10.4.2)

QT corrected for heart rate using Fridericia’s formula (QTcF)
The individual measurements and the mean of the triplicate measurements will be reported in the 
by-subject listings. The listing will also include the change from Baseline and percentage change 
from Baseline (based on the mean of the triplicate measurements at each timepoint) and will be 
presented by dose arm and timepoint.
Has been changed to:

QT corrected for heart rate using Fridericia’s formula (QTcF = QT/RR0.33)
The individual measurements and the mean of the triplicate measurements will be reported in the 
by-subject listings. The listing will also include the change from Baseline and percentage change 
from Baseline (based on the mean of the triplicate measurements at each timepoint). TEMA/PCS 
ECG values will be flagged in the listing.
Change #22
Electrocardiograms (Section 10.4.2)
The following table has been added:
Variable
Criteria
QT corrected for heart rate using 
Fridericia’s formula (QTcF)
≥501ms
OR
≥60ms compared to baseline
PR prolongation
≥210ms and ≥10ms change from 
baseline
Change #23
Classification of markedly abnormal laboratory values based in CTCAE grades (Section 
13.5)
Table 13-2 has been updated as follows:
Category
Panel
Variable
Criteria (CTCAE aGrade 3 and 
above)
Hematology
Red blood cell
Hemoglobin (Decrease)
<8g/dL (<80g/L)
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 113 of 128
Category
Panel
Variable
Criteria (CTCAE aGrade 3 and 
above)
Hemoglobin (Increase)
>4g/dL (>40g/L) above ULN 
OR
>4g/dL (>40g/L) above 
baseline if baseline is > ULN
White blood cell
WBC count (Decrease)
<2000/mm^3 
(<2.0x10^9/L)
WBC count (Increase)
>20,000/mm^3 
White blood cell 
differential
ALC (Decrease)
<500/mm^3 
(<0.5x10^9/L)
ALC (Increase)
>20,000/mm^3 
(>20x10^9/L)
ANC
<1000/mm^3 
(<1.0x10^9/L)
Chemistry
Liver Function
ALT
>5.0xULN
ALP
>5.0xULN
AST
>5.0xULN
Total bilirubin
>3.0xULN
GGT
>5.0xULN
Kidney Function
Creatinine
>3.0xbaseline value 
OR 
>3.0xULN
Creatinine (Acute 
kidney injury)
>3xbaseline value
OR
>4xULN
Creatinine 
phosphokinase
>5xULN
eGFR or CrCI
≤29ml/min/1.73m^2
Minerals
Calcium (Decrease)
corrected <7mg/dL 
(<1.75mmol/L); ionized <0.9 
mmol/L
Calcium (Increase)
corrected >13.5mg/dL 
(>3.1mmol/L); ionized 
>1.8mmol/L
Magnesium (Decrease)
<0.4mmol/L (<0.9mg/dL)
Magnesium (Increase)
>1.23mmol/L (>3mg/dL)
Phosphate
<0.6mmol/L (<2mg/dL)
Metabolic
Glucose (Decrease)
<2.2mmol/L (<40mg/dl)
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 114 of 128
Category
Panel
Variable
Criteria (CTCAE aGrade 3 and 
above)
Glucose (Increase)
>250mmol/L (>13.9mg/dl)
Electrolytes
Potassium (Decrease)
<3.0mmol/L
Potassium (Increase)
>6.0mmol/L
Sodium (Decrease)
<130mmol/L
Sodium (Increase)
>155mmol/L
Lipids
Total cholesterol
>10.34mmol/L (>400mg/dL)
Triglycerides
>5.7mmol/L (>500mg/dL)
Proteins
Albumin
<20g/L (<2g/dL)
Other
Amylase
>2.0xULN
14.3
Amendment 3
14.3.1
Rationale for the amendment
Various updates were suggested prior to and during the Data Evaluation Meeting in December 
2018.
14.3.2
List of changes
Change #1
Front page
SAP amendment 3 has been added:
Final SAP
07 Oct 2016
SAP Amendment 1 14 Nov 2017
SAP Amendment 2
14 May 2018
SAP Amendment 3
24 Jan 2019
Change #2
List of Abbreviations
The following abbreviations have been added:-
IVIg
intravenous immunoglobulin
TPO-R
thrombopoietin-receptor
Change #3
Introduction (4th paragraph)
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP amendment will be updated accordingly. In addition, if analysis definitions 
have to be modified or updated prior to database lock, a further SAP amendment will be 
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Statistical Analysis Plan
UCB7665
TP0001
Confidential
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required. If, after database lock, additional analyses are required to supplement the planned
analyses described in this SAP, these changes will be described in the CSR together with the 
associated rationale. The content of this SAP is compatible with the International Council for 
Harmonisation (ICH)/Food and Drug Administration (FDA) E9 Guidance documents.
Has been changed to:
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP amendment will be updated accordingly. In addition, if analysis definitions 
have to be modified or updated prior to database lock, a further SAP amendment will be 
required.
This SAP amendment 3 is due to various updates and clarifications of the analysis definitions 
suggested prior to and during the Data Evaluation Meeting 3 part 1 in December 2018.
If, after database lock, additional analyses are required to supplement the planned analyses 
described in this SAP, these changes will be described in the CSR together with the associated 
rationale. The content of this SAP is compatible with the International Council for 
Harmonisation (ICH)/Food and Drug Administration (FDA) E9 Guidance documents.
Change #4
Table 3-1 (Definition of Baseline)
The following footnote has been removed:
Error! Reference source not found.
Platelets measured locally are not measured at 
Screening.
Change #5
Full Analysis Set (Section 3.5.3)
The following paragraph has been added:
Platelet data for subjects who have taken rescue medications (based on medical review and 
defined in Section 8.1.4) will only be utilized in the summary tables up to the start of these 
rescue medications.
Change #6
Per Protocol Set (Section 3.5.4)
The Per Protocol Set (PPS) is a subset of the FAS, consisting of those subjects who had received 
all foreseen sc infusions, had a platelet count measurement (measured by ACM Global Central 
Laboratory) during the Observation Period, and no important protocol deviations that may 
potentially affect the platelet count as confirmed during a pre-analysis review of the data prior to 
database lock. Protocol deviations may not necessarily lead to total exclusion of a subject from 
the PPS but may lead to exclusion of specific data and/or timepoints from the analysis.
Has been changed to:
The Per Protocol Set (PPS) is a subset of the FAS, consisting of those subjects who had received 
all foreseen sc infusions, had a platelet count measurement (measured by ACM Global Central 
Laboratory) during the Observation Period, and no important protocol deviations that may 
potentially affect the platelet count as confirmed during a pre-analysis review of the data prior to 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 116 of 128
database lock. Protocol deviations may not necessarily lead to total exclusion of a subject from 
the PPS but may lead to exclusion of specific data and/or timepoints from the analysis.
Platelet data for subjects who have taken prohibited medications potentially affecting platelet 
counts such as PLEX, dexamethasone or rituximab (based on medical review) will only be 
utilised in the summary tables up to the start of these medications.
Change #7
Dates and times (Section 4.2.7, final bullet on partial stop dates)

If the stop date is completely unknown, do not impute the stop date
Has been changed to:

If the stop date is completely unknown, do not impute the stop date, except for ITP 
medications where end date is missing and ongoing is ticked as ‘no’, which will be imputed 
as “Past” medications.
Change #8
Examination of Subgroups (Section 4.8)
The following subgroups will be defined within each dose arm:

Use of corticosteroid medication: Present/Absent

Responder at the end of previous ITP treatment: No/Yes/Unknown

Previous tintravenous immunoglobulin (IVIG)  therapy: Yes/No 

Number of previous ITP therapies: ≤2/>2
Only medication classified as either ‘prior and concomitant’ or ‘concomitant’ and medical 
procedure will be considered for ITP treatment. Responder categories will be defined taking into 
account the last reported ITP treatment value (either Yes or No) for each patient. If this value is 
unknown, the second-last reported ITP treatment value will be used, then the third-last, and so 
on, until a known response is provided. The Unknown responder category will only be 
considered in cases where the investigator has never reported a category (Yes or No) for any of 
the previous ITP treatments. Past use of corticosteroids (not ongoing after dosing) will not be 
considered for this classification. The list of applicable Anatomical Therapeutic Chemical (ATC) 
codes in order to identify the presence/absence of corticosteroids is provided in Section 13.1.
The descriptive summaries for platelets and total IgG will be presented for the subgroups above. 
Has been changed to:
The following subgroups will be defined within each dose arm:

Concomitant corticosteroid medication: Yes/No
Concomitant medication is defined in Section 6.4.4. The list of applicable Anatomical 
Therapeutic Chemical (ATC) codes to be utilized as corticosteroids is provided in
Section 13.1.

Responder at the end of past ITP therapy: No/Yes/Unknown
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 117 of 128
Responder categories will be defined utilizing the value (either Yes or No) for the last 
reported ITP therapy for each patient. If this value is unknown, the second-last reported ITP 
therapy value will be used, then the third-last, and so on, until a known response is provided. 
The Unknown responder category will only be considered in cases where the investigator has 
never reported a category (Yes or No) for any of the past ITP therapies. For the ‘Response’ 
definition, the CRF entries will be utilized.
The past ITP therapy is defined as procedure history related to ITP or past medication related 
to ITP, where past medication is defined in Section 6.4.1. For ‘related to ITP’ CRF entries 
will be utilized.
The corticosteroid medication given more than 3 months prior to screening was routinely not 
recorded and cannot be considered. Thus, some patients with an unknown response might 
have had a known response.

Past intravenous immunoglobulin (IVIg) medication: Yes/No
Past medication is defined in Section 6.4.1. The ATC Therapeutic Subgroup code (Level 2) 
‘IMMUNE SERA AND IMMUNOGLOBULINS’ will be utilized.

Number of past ITP therapies: ≤2/>2
The past ITP therapy is defined as procedure history related to ITP or past medication related 
to ITP, where past medication is defined in Section 6.4.1. For ‘related to ITP’ CRF entries 
will be utilized.
The corticosteroid medication given more than 3 months prior to screening was routinely not 
recorded and cannot be considered. Thus, some patients might have had 1 more past ITP 
therapy than utilized for subgroup determination.
The descriptive summaries for platelets and total IgG will be presented for the subgroups above. 
Change #9
Past, prior and concomitant medications (Section 6.4)
Past, prior and concomitant medications will be summarized for the SS by dose arm and for all 
subjects by WHODD Anatomical Main Group [Level 1], Therapeutic Subgroup [Level 2] and 
PT. 
Separate tabulations will be presented for the following:

Past medications

Prior and concomitant medications

Concomitant medications
All medications will be listed and will include coding information, reported term, dose per intake 
and unit, frequency, formulation, route of administration, indication, category (past/prior and 
concomitant/concomitant) and start and end date (or ongoing, if applicable).
Has been changed to:
Past, prior, baseline and concomitant medications
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 118 of 128
Past, prior, baseline and concomitant medications will be summarized for the SS by dose arm 
and for all subjects by WHODD Anatomical Main Group [Level 1], Therapeutic Subgroup 
[Level 2] and PT.
All medications will be listed and will include coding information, reported term, dose per intake 
and unit, frequency, formulation, route of administration, indication, category (past/prior and 
concomitant/concomitant) and start and end date (or ongoing, if applicable).
Change #10
This section has been added:-
Baseline Medication (Section 6.4.3)
Baseline medications will include any medications that started prior to dosing and continued 
after (classified as prior and concomitant medications).
Change #11
Concomitant medication definition (Section 6.4.4)
Concomitant medications will include any medication that has been taken at least once (after the 
first administration of UCB7665) during the Dosing Period and/or the Observation Period.
Any medication that started prior to the first administration of UCB7665 and continued after 
dosing will be classified as prior and concomitant. Any medication that started after the first 
administration of UCB7665 will be classified as concomitant only.
Any medications with missing dates and/or times will be handled as described in Section 4.2.7 in 
order to classify them as prior and/or concomitant.
Has been changed to:
Concomitant medications will include any medication that has been taken at least once (after the 
first administration of UCB7665) during the Dosing Period and/or the Observation Period.
This includes medications that started prior to the dosing and continued after (classified as prior 
and concomitant medications) as well as any medication that started after the first administration 
of UCB7665 (classified as concomitant).
Any medications with missing dates and/or times will be handled as described in Section 4.2.7 in 
order to classify them as prior and/or concomitant.
Change #12
Platelets (Section 8.1)
All efficacy analyses are based on platelet count measured by ACM Global Central Laboratory. 
Measurements of platelet count obtained by the local laboratory will be listed and summarized as 
part of the safety laboratory data. These are not included in the analyses described in the sections 
below. All tabulations and mean figures will be presented for both the FAS and the PPS unless 
otherwise stated. Median figures and individual figures will be presented for the FAS only. In 
case rescue medications are taken, only the platelet data up to the start date of rescue medication  
will be utilized for the summary tables. Listings will contain all the data but a footnote will be 
included indicating the patients for which some data has been excluded from the summary tables.
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UCB
07 Nov 20168
Statistical Analysis Plan
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TP0001
Confidential
Page 119 of 128
In case of partial dates, the imputation rules for partial dates described in Section 4.2.7 will be 
applied.
Has been changed to:
All efficacy analyses are based on platelet count measured by ACM Global Central Laboratory. 
Measurements of platelet count obtained by the local laboratory will be listed and summarized as 
part of the safety laboratory data. These are not included in the analyses described in the sections 
below. All tabulations and mean figures will be presented for both the FAS and the PPS unless 
otherwise stated. Median figures and individual figures will be presented for the FAS only. In 
case rescue medications are taken, only the platelet data up to the start date of rescue medication 
will be utilized for the summary tables (refer to Section 8.1.4). In case prohibited medications 
affecting platelets are taken, only the platelet data up to the start date of prohibited medication 
will be utilized for the summary tables for the PPS (refer to Section 3.4). Listings will contain all 
the data but a footnote will be included indicating the patients for which some data has been 
excluded from the summary tables. In case of partial dates, the imputation rules for partial dates 
described in Section 4.2.7 will be applied.
Change #13
Definition of Variables (Section 8.1.1)
The main efficacy variable is defined as the following: 

Maximum Increase from Baseline: the Maximum Increase from Baseline (Day 1, predose) is 
defined as the highest positive change from Baseline during the study. In the event that the 
platelet count was to decrease during the study the Maximum Increase from Baseline may be 
negative and would correspond to the smallest decrease from the Baseline value
The following additional variables will be defined for the platelet count, the calculation rules for 
which are provided in the section immediately below:

Response: a Response is defined as a platelet count ≥30x109/L and at least 2-fold increase 
from the Baseline value, by visit, and at any timepoint during the study

Time to Response: the time to Response is defined as the time from starting treatment 
(Day 1) to achievement of Response

Duration of Response: the duration of Response is defined as the time between achievement 
of a Response to the first time a loss of Response occurred (defined as platelet count <30 x 
109/L or less than 2-fold increase from Baseline)

Complete Response: a Complete Response is defined as a platelet count ≥100x109/L, by 
visit, and at any timepoint during the study

Time to Complete Response: the time to Complete Response is defined as the time from 
starting treatment (Day 1) to achievement of Complete Response

Duration of Complete Response: the duration of Complete Response is defined as the time 
between achievement of a Complete Response to the first time a loss of Complete Response 
occurred (defined as platelet count <100x109/L)

Platelet Count ≥50x109/L, by visit, and at any timepoint during the study
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UCB
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Statistical Analysis Plan
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Page 120 of 128

Time to Platelet Count ≥50x109/L: the time to Platelet Count ≥50x109/L is defined as the 
time from starting treatment (Day 1) to achievement of Platelet Count ≥50x109/L

Duration of Platelet Count ≥50x109/L: the duration of a Platelet Count ≥50x109/L is defined 
as the time between achievement of a Platelet Count ≥50x109/L to the first time the platelet 
count is <50x109/L

Maximum: the maximum value for platelet count over all visits in the study

Value and change from Baseline in platelet count over time

Baseline-corrected AUEC for platelet count calculated from Baseline to the end of study visit 
for each of the defined dose arms.
For all the above response variables the following rules will apply:

The time to response (including Complete Response, Response and Platelet Count 
≥50x109/L) is defined as the first time that a given response is achieved during the study. 
Thus, in the event that the platelet count was to increase above the threshold level, decrease 
below the threshold level, and subsequently increase again the time to response would be to 
the first time the definition of response was achieved. The time to response will be calculated 
in days and presented to 1 decimal place in the listings.
Time to response (days) = Date/time of first response – Date/time of first dose of UCB7665

The duration of response (including Complete Response, Response and Platelet Count 
≥50x109/L) will be defined as the duration of the first time the response was achieved to loss 
of first response. The duration of response will be calculated in days and presented to 1 
decimal place in the listings.
Duration of response (days) = Date/time of loss of first response – Date/time of first response
If the platelet value meets the criterion for a specific response for a second time (following a 
loss of initial response), the second response period will be added to the overall duration of 
response. This rule will be applied for any subsequent ‘response periods’. For subject in 
whom the response is maintained until the end of the study the duration of response will be 
calculated using the date of the end of study visit as the ‘end of response date’. Any such 
cases will be flagged in the data listings

Both scheduled and unscheduled measurements may be included in the calculation of a 
response, time to response or duration of response

The Baseline-corrected AUEC will be calculated according to the following rules:

The AUEC will be calculated according to the linear trapezoidal rule using protocol 
scheduled visits

Unscheduled visits will not be included in the calculation

No imputation of any missing data will be performed

To account for differences in the timing of Baseline samples for each subject the Baseline 
measurement will be considered as time zero in the calculation

The units of the AUEC will be 109/L*day
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 121 of 128

The measurements at Baseline and at the last visit must be available

A minimum of 10 out of 14 measurements must be available for the calculation in Dose 
Arm 1; a minimum of 9 out of 12 measurements must be available for the calculation in 
Dose Arm 2; a minimum of 8 out of 11 must be available for the calculation in Dose Arm 
3; a minimum of 7 out of 9 must be available for the calculation in Dose Arms 4 and 5. 
These include the Baseline and measurement at the last visit

The AUEC will not be calculated in the case of early withdrawal from the study
Has been changed to:
The main efficacy variable is defined as the following: 

Maximum Increase from Baseline: the Maximum Increase from Baseline (Day 1, predose) is 
defined as the highest positive change from Baseline during the study. In the event that the 
platelet count was to decrease during the study the Maximum Increase from Baseline may be 
negative and would correspond to the smallest decrease from the Baseline value
The following additional variables will be defined for the platelet count, the calculation rules for 
which are provided in the section immediately below:

Response: a platelet count ≥30x109/L and at least 2-fold increase from the Baseline value, by 
visit, and at any timepoint during the study

Time to Response: the first time that a given response is achieved during the study. Thus, in 
the event that the platelet count was to increase above the threshold level, decrease below the 
threshold level, and subsequently increase again the time to response would be to the first 
time the definition of response was achieved. The time to response will be calculated in days 
and presented to 1 decimal place in the listings.
Time to response (days) = Date/time of first response – Date/time of first dose of UCB7665

‘No’ or ‘Loss of’ Response: a platelet count <30x109/L OR >=30x109/L WITHOUT at least 
a 2-fold increase from the Baseline value, by visit

Duration of Response (including Complete Response, Response and Platelet Count 
≥50x109/L): the duration of the first time the response was achieved to first loss of response. 
The duration of response will be calculated in days and presented to 1 decimal place in the 
listings.
Duration of response (days) = Date/time of loss of first response – Date/time of first 
response, where “loss of first response” is defined as platelet count<30x109/L OR (platelet 
count ≥30x109/L WITHOUT at least a 2-fold increase from the Baseline value)
If the platelet value meets the criterion for a specific response for a second time (following a 
loss of initial response), the second response period will be added to the overall duration of 
response. This rule will be applied for any subsequent ‘response periods’. For subject in 
whom the response is maintained until the end of the study the duration of response will be 
calculated using the date of the end of study visit as the ‘end of response date’. Any such 
cases will be flagged in the data listings
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 122 of 128

Complete Response: a platelet count ≥100x109/L, by visit, and at any timepoint during the 
study

‘No’ or ‘Loss of’ Complete Response: a platelet count <100x109/L, by visit.

Time to Complete Response: the time from starting treatment (Day 1) to achievement of 
Complete Response

Platelet Count ≥50x109/L, by visit, and at any timepoint during the study

‘No’ or ‘Loss of’ Platelet Count ≥50x109/L: a platelet count <50x109/L, by visit.

Time to Platelet Count ≥50x109/L: the time to Platelet Count ≥50x109/L is defined as the 
time from starting treatment (Day 1) to achievement of Platelet Count ≥50x109/L

Maximum: the maximum value for platelet count over all visits in the study

Value and change from Baseline in platelet count over time

Baseline-corrected AUEC for platelet count calculated from Baseline to the end of study visit 
for each of the defined dose arms.
For all the above response variables the following rules will apply:

Both scheduled and unscheduled measurements may be included in the calculation of a 
response, time to response or duration of response

The Baseline-corrected AUEC will be calculated according to the following rules:

The AUEC will be calculated according to the linear trapezoidal rule using protocol 
scheduled visits

Unscheduled visits will not be included in the calculation

No imputation of any missing data will be performed

To account for differences in the timing of Baseline samples for each subject the Baseline 
measurement will be considered as time zero in the calculation

The units of the AUEC will be 109/L*day

The measurements at Baseline and at the last visit must be available

A minimum of 10 out of 14 measurements must be available for the calculation in Dose 
Arm 1; a minimum of 9 out of 12 measurements must be available for the calculation in 
Dose Arm 2; a minimum of 8 out of 11 must be available for the calculation in Dose Arm 
3; a minimum of 7 out of 9 must be available for the calculation in Dose Arms 4 and 5. 
These include the Baseline and measurement at the last visit

The AUEC will not be calculated in the case of early withdrawal from the study
Change #14
Analysis of Time to Response (Section 8.1.3.2)
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 123 of 128
The time to first response will be analyzed with the log-rank test and displayed using Kaplan-
Meier curves. Each response parameter will be considered in a separate analysis. The following 
parameters will be included in the analysis:

Time to Response: the time to Response is defined as the time from starting treatment 
(Day 1) to achievement of Response (platelet count ≥30x109/L and at least 2-fold increase 
from the Baseline value)

Time to Complete Response: the time to Complete Response is defined as the time from 
starting treatment (Day 1) to achievement of Complete Response (platelet count ≥100x109/L)

Time to Platelet Count ≥50x109/L
Kaplan-Meier curves will be presented for all three response parameters. Descriptive statistics 
will include the p-value for the log-rank test for the equality over dose arms. The point estimate 
for the median number of days to response with 90% CIs will be given if estimable. Further a 
summary including the number and percent of censored subjects, the number of responders and 
total subjects by dose arm and in total will be given.
For the purpose of the analysis subjects with no response will be censored at the end of the study 
or at the date of withdrawal.
Analyses will be performed for the FAS and repeated for the PPS.
Has been changed to:
The time to first response will be analyzed with the log-rank test and displayed using Kaplan-
Meier curves.
Kaplan-Meier curves will be presented for the variables Time to Response, Time to Complete 
Response, and Time to Platelet Count ≥50x109/L. Descriptive statistics will include the p-value 
for the log-rank test for the equality over dose arms. The point estimate for the median number of 
days to response with 90% CIs will be given if estimable. Further a summary including the 
number and percent of censored subjects, the number of responders and total subjects by dose 
arm and in total will be given.
For the purpose of the analysis subjects with no response will be censored at the end of the study 
or at the date of withdrawal.
Analyses will be performed for the FAS and repeated for the PPS.
Change #15
Analysis of responder rate (Section 8.1.3.3, 3rd paragraph)
Analyses will be performed for the FAS and repeated for the PPS. Summary tabulations by dose 
arm will be repeated for the subgroups defined in Section 4.8 (based on the FAS only).
Moreover, for responder rate, summary tabulations by dose arm will be repeated according to 
previous intravenous immunoglobulin therapy (Yes/No) and the number of previous medications 
(≤2/>2). Percentage of days without bleeding will also be described by dose arm for each type of 
response (response, complete response and platelet Count >=50x10/L). Percentage of days 
without bleeding is calculated using the following formula:
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 124 of 128
((N of visits with a SMOG score – N of these visits where bleeding occurred) / N of visits with a 
SMOG score) x 100
Has been changed to:
Analyses will be performed for the FAS and repeated for the PPS. Summary tabulations by dose 
arm will be repeated for the subgroups defined in Section 4.8 (based on the FAS only).
Percentage of days without bleeding will also be described by dose arm for each type of response 
(response, complete response and platelet Count >=50x10/L). Percentage of days without 
bleeding is calculated using the following formula:
((N of visits with a SMOG score – N of these visits where bleeding occurred) / N of visits with a 
SMOG score) x 100
Change #16
The following section has been added:
Rescue medication definition (after medical inspection) (Section 8.1.4)
In the rescue medication section of the protocol, rescue medication is defined as platelet 
substitution or treatment with a commercially available IVIg. In addition, the prohibited 
medications PLEX, dexamethasone and rituximab will also be considered as a rescue medication 
for analysis.
Change #17
ITP bleeding score and platelet response (Section 8.2.1.1)
In addition to the platelet response variables defined in Section 8.1.1 the following variables will 
also be defined based on a combination of platelet response and information from the ITP 
bleeding score (these will be referred to as Clinical Response variables). In case rescue 
medications or prohibited medications potentially affecting platelet counts are taken, only the 
platelet data up to the start date of rescue medication will be utilized for the summary tables
(refer to Section 8.1.4):

Clinical Response: a Clinical Response is defined as a platelet count ≥30x109/L and 
<100x109/L with at least 2-fold increase from the Baseline value AND absence of bleeding, 
by visit, and at any timepoint during the study

Time to Clinical Response: the time to Clinical Response is defined as the time from starting 
treatment (Day 1) to achievement of Clinical Response

Duration of Clinical Response: the duration of Clinical Response is defined as the time 
between achievement of a Clinical Response to the first time a loss of Clinical Response 
occurred (defined as platelet count <30x109/L or less than 2-fold increase from Baseline OR 
presence of bleeding)

Complete Clinical Response: a Complete Clinical Response is defined as a platelet count 
≥100x109/L AND absence of bleeding, by visit, and at any timepoint during the study

Time to Complete Clinical Response: the time to Complete Clinical Response is defined as 
the time from starting treatment (Day 1) to achievement of Complete Clinical Response
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 125 of 128

Duration of Complete Clinical Response: the duration of Complete Clinical Response is 
defined as the time between achievement of a Complete Clinical Response to the first time a 
loss of Complete Clinical Response occurred (defined as platelet count <100x109/L OR 
presence of bleeding)

No Clinical Response: a platelet count <30x109/L and less than 2-fold increase from Baseline 
OR presence of bleeding, by visit, and at any timepoint during the study
For all the above response criteria, the calculation rules included in Section 8.1.1 will apply. In 
addition the following will be applicable:

The clinical response variables will be assessed only for visits for which both platelet counts 
and the ITP bleeding score are assessed (with the exception of the confirmatory platelet 
assessments which may be obtained at any visit [scheduled or unscheduled] provided that 
they meet the criteria below)

In order to define a clinical response, the platelet count must be confirmed on 2 separate 
occasions at least 7 days apart (i.e., the second assessment should be ≥168 hours after the 
first assessment). The time to response will be taken as the time to the first platelet 
assessment (obtained at the same time as the corresponding ITP bleeding score assessment). 
If the second assessment does not fulfill the required criteria for a clinical response, the 
subject will be considered as a nonresponder at the respective visits

In order to define no response or a loss of response, the platelet count must be confirmed on 
2 separate occasions within 1 to 7 days* (i.e., the second assessment should be ≥24 hours and 
≤168 hours after the first assessment). The loss of response will be taken as the point at 
which the first platelet assessment was obtained (obtained at the same time as the 
corresponding ITP bleeding score assessment). If the second assessment does not fulfill the 
required criterion for no response or loss of response, the subject will be considered as a 
responder at the respective visits

Absence of bleeding is indicated by Grade 0 for all domains of the SMOG

Presence of bleeding is indicated by a Grade of 1 or above, for at least one domain of the 
SMOG
*This differs from the published definition (Rodeghiero et al, 2009) which requires 2 platelet 
measurements 1 day apart to define no response or loss of response. In the current protocol 
platelet count assessments are not as frequently planned (unless unscheduled measurements are 
performed), thus it was deemed appropriate to modify the definition above to take into account 
the schedule of assessments in this study. 
As a result the following clinical response variables are not in complete accordance with the 
guideline:

Duration of Clinical Response

Duration of Complete Clinical Response

No Clinical Response
All response variables described above will be listed by dose arm and subject and summarized 
by dose arm and visit where appropriate. The responder rates will be tabulated as described in 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 126 of 128
Section 8.1.3.3. Moreover the change in category of bleeding from Baseline will also be 
presented in shift table at all post-Baseline visits by dose arm. Summary tabulations for Clinical 
Response by dose arm will be repeated according to past intravenous immunoglobulin 
medication (Yes/No) and the number of past ITP therapies (≤2/>2). All analyses described in this 
section will be performed for the FAS.
In case rescue medications are taken, only the data up to the start date of rescue medication  will 
be utilized for the summary tables. Listings will contain all the data but a footnote will be 
included indicating the patients for which some data has been excluded from the summary tables.
In case of partial dates, the imputation rules for partial dates described in Section 4.2.7 will be 
applied.
Has been changed to:
In addition to the platelet response variables defined in Section 8.1.1 the following variables will 
also be defined based on a combination of platelet response and information from the ITP 
bleeding score (these will be referred to as Clinical Response variables). In case rescue 
medications are taken, only the platelet data up to the start date of rescue medication will be 
utilized for the summary tables (refer to Section 8.1.4):

Clinical Response: a Clinical Response is defined as a platelet count ≥30x109/L with at least 
2-fold increase from the Baseline value AND absence of bleeding, by visit. This must be 
confirmed by a second measurement at least 5 days later (to allow for the ±2-day visit 
window), showing a platelet count ≥30x109/L and at least 2-fold increase from the Baseline.

Time to Clinical Response is defined as the time from starting treatment (Day 1) to 
achievement of Clinical Response. The will be taken as the time to the first platelet 
assessment (obtained at the same time as the corresponding ITP bleeding score assessment). 
If the second assessment does not fulfill the required criteria for a clinical response, the 
subject will be considered as a nonresponder at the respective visits.

Duration of Clinical Response: the duration of Clinical Response is defined as the time 
between achievement of a Clinical Response to the first time a loss of Clinical Response 
occurred (defined as platelet count <30x109/L or less than 2-fold increase from Baseline OR 
presence of bleeding). Refer to Section 8.1.1 in case a subject has several clinical responses 
or the clinical response is maintained until the end of the study".

Complete Clinical Response: a Complete Clinical Response is defined as a platelet count 
≥100x109/L AND absence of bleeding, by visit. This must be confirmed by a second 
measurement at least 5 days later (to allow for the ±2-day visit window), showing a platelet 
count ≥100x109/L.

Time to Complete Clinical Response: the time to Complete Clinical Response is defined as 
the time from starting treatment (Day 1) to achievement of Complete Clinical Response

Duration of Complete Clinical Response: the duration of Complete Clinical Response is 
defined as the time between achievement of a Complete Clinical Response to the first time a 
loss of Complete Clinical Response occurred (defined as platelet count <100x109/L OR 
presence of bleeding). Refer to Section 8.1.1 in case a subject has several clinical responses 
or the clinical response is maintained until the end of the study". 
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 127 of 128

No Clinical Response or a loss of clinical response: the platelet count must be defined as a 
platelet count <30x109/L OR >=30x109/L WITHOUT at least a 2-fold increase from the 
Baseline value OR presence of bleeding, by visit. This must be confirmed by a second 
measurement 1 to 9 days* later, showing a platelet count <30x109/L OR >=30x109/L 
WITHOUT at least a 2-fold increase from the Baseline value.
For all the above response criteria, the calculation rules included in Section 8.1.1 will apply. In 
addition the following will be applicable:

The Clinical Response variables will be assessed only for visits for which both platelet 
counts and the ITP bleeding score are assessed. The last visit cannot be a clinical response as 
no confirmation after that is available.

Absence of bleeding is indicated by Grade 0 for all domains of the SMOG, or a Skin Grade 
of 0 or 1

Presence of bleeding is indicated by a Mucosae or Organs Grade of ≥1, or Skin Grade of ≥2
*This differs from the published definition (Rodeghiero et al, 2009) which requires 2 platelet 
measurements 1 day apart to define no response or loss of response. In the current protocol 
platelet count assessments are not as frequently planned (unless unscheduled measurements are 
performed), thus it was deemed appropriate to modify the definition above to take into account 
the schedule of assessments in this study. 
As a result the following clinical response variables are not in complete accordance with the 
guideline:

Duration of Clinical Response

Duration of Complete Clinical Response

No Clinical Response
All response variables described above will be listed by dose arm and subject and summarized 
by dose arm and visit where appropriate. The responder rates will be tabulated as described in 
Section 8.1.3.3. Moreover the change in category of bleeding from Baseline will also be 
presented in shift table at all post-Baseline visits by dose arm. Summary tabulations for Clinical 
Response by dose arm will be repeated according to past intravenous immunoglobulin 
medication (Yes/No) and the number of past medications (≤2/>2). All analyses described in this 
section will be performed for the FAS.
In case rescue medications are taken, only the data up to (not including) the start date of rescue 
medication will be utilized for the summary tables. Listings will contain all the data but a 
footnote will be included indicating the patients for which some data has been excluded from the 
summary tables. In case of partial dates, the imputation rules for partial dates described in 
Section 4.2.7 will be applied.
Change #18
Table 10-1 (Clinical laboratory measurements)
HbA1c has been moved from the Hematology category to the “Other” category.
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UCB
07 Nov 20168
Statistical Analysis Plan
UCB7665
TP0001
Confidential
Page 128 of 128
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE
This document has been reviewed and approved per the Review and Approval of Clinical 
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Approval Signatures
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Version:
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Document Number:
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Title:
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Approved Date:
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Verdict: Approved
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Date of Signature: 29-Jan-2019 08:30:39 GMT+0000
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