Conditions: Myasthenia Gravis
Keywords: UCB7665 Myasthenia Gravis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 43
Healthy volunteers: no

Brief summary:
The purpose of the study is to evaluate the clinical efficacy of UCB7665 as a chronic-intermittent treatment in subjects with generalized myasthenia gravis (MG) who are classified as moderate to severe.

Detailed description:

Arms:
arm 1: Subjects randomized in dosage regimen 1 will receive 3 doses of UCB7655 (dose 1) in dosing period 1 and will then be re-randomized into dosing period 2 to receive 3 doses of UCB7665 (dose 1 or dose 2). arm 2: Subjects randomized in dosage regimen 2 will receive 3 doses of placebo in dosing period 1 and will then be re-randomized into dosing period 2 to receive 3 doses of UCB7665 (dose 1 or dose 2).

Interventions: intervention 1: UCB7665 intervention 2: Placebo
Intervention descriptions: intervention 1: UCB7665 will be administered in 2 different dosages (dose 1 and dose 2). UCB7665 (INN: Rozanolixizumab) is a humanized monoclonal antibody that is being developed for treatment of IgG autoantibody-mediated conditions such as myasthenia gravis (MG) intervention 2: Placebo will be administered in period 1 of dosage regimen 2.

Protocol document:
Prot_002.pdf: 
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PROTOCOL MG0002
A MULTICENTER, RANDOMIZED, INVESTIGATOR- AND 
SUBJECT-BLIND, PLACEBO-CONTROLLED, TREATMENT 
SEQUENCE STUDY EVALUATING THE SAFETY, 
TOLERABILITY, AND EFFICACY OF UCB7665 IN SUBJECTS 
WITH MODERATE TO SEVERE MYASTHENIA GRAVIS 
PHASE 2A
EudraCT Number: 2016-002698-36
IND Number: 132407 
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
21 Oct 2016
Not applicable
Protocol Amendment 1
07 Feb 2017
Substantial
Protocol Amendment 2
15 Sep 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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STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Principal/Coordinating Investigator
Name:
Dr. Vera Bril
Affiliation:
-
Address:
Toronto General Hospital
200 Elizabeth St. 
Toronto, ON 
Canada
Phone:
Fax:
Sponsor Study Physician
Name:
Address:
UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
Fax:
-
Clinical Project Manager
Name:
Address:
GCSO Clinical Project Management
UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617   
UNITED STATES
Phone:
Fax:
-
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Clinical Trial Biostatistician
Name:
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name:
PAREXEL International (IRL) Limited
Address:
70 Sir John Rogerson’s Quay
Dublin 2
IRELAND
Phone:
+353 1 473 9500
Fax:
+353 1 477 3390
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SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 6561
USA and Canada: 011 32 2 386 65 61
Email
Global: safetyreportingUCB7665@ucb.com
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TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................11
1
SUMMARY.....................................................................................................................14
2
INTRODUCTION ...........................................................................................................15
3
STUDY OBJECTIVES....................................................................................................18
3.1 Primary objective.............................................................................................................18
3.2 Secondary objectives .......................................................................................................18
3.3 Exploratory objectives .....................................................................................................18
4
STUDY VARIABLES.....................................................................................................19
4.1 Efficacy variables.............................................................................................................19
4.1.1
Primary efficacy variable.....................................................................................19
4.1.2
Secondary efficacy variable.................................................................................19
4.1.3
Other efficacy variables.......................................................................................19
4.2 Other and exploratory variables.......................................................................................20
4.2.1
Safety variables....................................................................................................20
4.2.2
Pharmacokinetic variable.....................................................................................20
4.2.3
Pharmacodynamic variables ................................................................................20
4.2.4
Immunological variables .....................................................................................21
5
STUDY DESIGN.............................................................................................................21
5.1 Study description .............................................................................................................21
5.1.1
Exploratory genomic analyses.............................................................................23
5.1.2
Study duration per subject ...................................................................................23
5.1.3
Planned number of subjects and sites ..................................................................23
5.1.4
Anticipated regions and countries .......................................................................23
5.2 Schedule of study assessments.........................................................................................24
5.3 Schematic diagram...........................................................................................................31
5.4 Rationale for study design and selection of dose.............................................................31
5.4.1
Choice of study design and endpoints .................................................................31
5.4.2
Rationale for dose selection.................................................................................32
5.4.3
Justification for additional genomic analyses......................................................33
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................34
6.1 Inclusion criteria ..............................................................................................................34
6.2 Exclusion criteria .............................................................................................................35
6.2.1
Exclusion criteria related to health status ............................................................35
6.2.2
Exclusion criteria related to concomitant medications/procedures .....................37
6.2.3
Exclusion criteria related to other risks ...............................................................38
6.3 Rescreening and Rechecking ...........................................................................................38
6.4 Withdrawal criteria ..........................................................................................................39
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6.4.1
Potential drug-induced liver injury IMP discontinuation criteria........................40
7
STUDY TREATMENT...................................................................................................41
7.1 Description of investigational medicinal product............................................................41
7.2 Treatments to be administered.........................................................................................41
7.3 Packaging.........................................................................................................................42
7.4 Labeling ...........................................................................................................................42
7.5 Handling and storage requirements..................................................................................42
7.6 Drug accountability..........................................................................................................42
7.7 Procedures for monitoring subject compliance................................................................43
7.8 Concomitant medication/treatment..................................................................................43
7.8.1
Permitted concomitant medication ......................................................................43
7.8.2
Prohibited concomitant treatments (medications and therapies).........................44
7.8.3
Rescue medication...............................................................................................44
7.9 Blinding............................................................................................................................45
7.9.1
Procedures for maintaining and breaking the treatment blind.............................45
7.9.1.1
Maintenance of study treatment blind.......................................................45
7.9.1.2
Breaking the treatment blind in an emergency situation...........................45
7.10 Randomization and numbering of subjects......................................................................46
8
STUDY PROCEDURES BY VISIT ...............................................................................46
8.1 Screening Period ..............................................................................................................46
8.1.1
Visit 1 (Day -28 to -1) Screening Visit................................................................46
8.2 Dosing Period 1................................................................................................................47
8.2.1
Visit 2 (Day 1, Baseline) .....................................................................................48
8.2.2
Visit 3 (Day 2) .....................................................................................................49
8.2.3
Visit 4 (Day 8) .....................................................................................................49
8.2.4
Visit 5 (Day 9) .....................................................................................................51
8.2.5
Visit 6 (Day 15) ...................................................................................................51
8.2.6
Visit 7 (Day 16) ...................................................................................................52
8.2.7
Visit 8 (Day 22) ...................................................................................................52
8.3 Dosing Period 2................................................................................................................53
8.3.1
Visit 9 (Day 29) ...................................................................................................53
8.3.2
Visit 10 (Day 30) .................................................................................................55
8.3.3
Visit 11 (Day 36) .................................................................................................55
8.3.4
Visit 12 (Day 37) .................................................................................................57
8.3.5
Visit 13 (Day 43) .................................................................................................57
8.3.6
Visit 14 (Day 44) .................................................................................................58
8.4 Observation Period...........................................................................................................58
8.4.1
Visit 15 (Day 50) .................................................................................................58
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8.4.2
Visit 16 (Day 57) .................................................................................................59
8.4.3
Visit 17 (Day 64) .................................................................................................60
8.4.4
Visit 18 (Day 78) .................................................................................................61
8.4.5
Visit 19 (Day 92) .................................................................................................62
8.4.6
Visit 20 (Day 99, Final Visit) and Premature End of Treatment Visit................63
8.5 Premature End of Treatment Visit ...................................................................................64
8.6 Unscheduled Visit............................................................................................................64
9
ASSESSMENT OF EFFICACY......................................................................................65
9.1 Quantitative Myasthenia Gravis scale..............................................................................65
9.2 MG-Composite scale .......................................................................................................65
9.3 Patient-reported outcomes ...............................................................................................65
9.3.1
MG muscle weakness and fatigability.................................................................65
9.3.2
Fatigue .................................................................................................................66
9.3.3
MG-Activities of Daily Living............................................................................66
9.3.4
Myasthenia Gravis Impairment Index .................................................................66
9.4 MGFA classification........................................................................................................66
9.5 Jitter (Single Fiber Electromyography) ...........................................................................67
9.6 Subject exit interview ......................................................................................................67
10
ASSESSMENT OF PHARMACOKINETIC/ 
PHARMACODYNAMIC/PHARMACOGENOMIC VARIABLES..............................67
10.1 Pharmacokinetic variable.................................................................................................67
10.2 Pharmacodynamic variables ............................................................................................67
11
ASSESSMENT OF OTHER VARIABLES ....................................................................68
11.1 Assessment of other immunological variables.................................................................68
12
ASSESSMENT OF SAFETY..........................................................................................69
12.1 Adverse events.................................................................................................................69
12.1.1
Definitions ...........................................................................................................69
12.1.1.1
Adverse event............................................................................................69
12.1.1.2
Serious adverse event ................................................................................69
12.1.1.3
Adverse events of special interest .............................................................70
12.1.1.4
Adverse events of interest .........................................................................70
12.1.1.5
Immediate reporting of adverse events......................................................70
12.1.2
Procedures for reporting and recording adverse events.......................................71
12.1.2.1
Description of adverse events....................................................................71
12.1.2.2
Rule for repetition of an adverse event......................................................71
12.1.2.3
Additional procedures for reporting serious adverse events .....................71
12.1.3
Follow up of adverse events ................................................................................72
12.1.4
Pregnancy ............................................................................................................72
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12.1.5
Suspected transmission of an infectious agent via a medicinal product..............73
12.1.6
Suicidality............................................................................................................73
12.1.7
Overdose of investigational medicinal product ...................................................74
12.1.8
Safety signal detection.........................................................................................74
12.1.9
Hypersensitivity and adverse reactions ...............................................................74
12.1.10
Management of severe headache.........................................................................75
12.1.11
Management of moderate or severe diarrhea.......................................................75
12.2 Laboratory measurements................................................................................................75
12.2.1
Evaluation of PDILI ............................................................................................77
12.2.1.1
Consultation with medical monitor and local hepatologist.......................81
12.2.1.2
Immediate action: determination of IMP discontinuation.........................81
12.2.1.3
Testing: identification/exclusion of alternative etiology...........................82
12.2.1.4
Follow-up evaluation.................................................................................83
12.3 Other safety measurements..............................................................................................84
12.3.1
Assessment and management of TB and TB risk factors....................................84
12.3.2
Pregnancy testing.................................................................................................85
12.3.3
Vital signs ............................................................................................................86
12.3.4
Body weight and height.......................................................................................86
12.3.5
Physical examination...........................................................................................86
12.3.5.1
Full physical examination .........................................................................86
12.3.5.2
Brief physical examination........................................................................87
12.3.6
Neurological examination....................................................................................87
12.3.7
12-lead ECG ........................................................................................................87
13
STUDY MANAGEMENT AND ADMINISTRATION.................................................88
13.1 Adherence to protocol......................................................................................................88
13.2 Monitoring .......................................................................................................................88
13.2.1
Definition of source data .....................................................................................88
13.2.2
Source data verification .......................................................................................89
13.3 Data handling...................................................................................................................89
13.3.1
Case Report Form completion.............................................................................89
13.3.2
Database entry and reconciliation........................................................................89
13.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............89
13.4 Termination of the study..................................................................................................90
13.5 Archiving and data retention............................................................................................90
13.6 Audit and inspection ........................................................................................................90
13.7 Good Clinical Practice .....................................................................................................91
14
STATISTICS ...................................................................................................................91
14.1 Definition of analysis sets................................................................................................91
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14.2 General statistical considerations.....................................................................................92
14.3 Planned efficacy analyses ................................................................................................92
14.3.1
Analysis of the primary efficacy variable............................................................92
14.3.2
Other efficacy analyses........................................................................................93
14.4 Planned other and exploratory analyses...........................................................................94
14.4.1
Safety analyses.....................................................................................................94
14.4.2
Pharmacokinetic analysis.....................................................................................94
14.4.3
Pharmacodynamic analysis..................................................................................95
14.4.4
Immunological variables .....................................................................................95
14.4.5
Subject exit interview ..........................................................................................95
14.5 Handling of protocol deviations.......................................................................................95
14.6 Handling of dropouts or missing data..............................................................................95
14.7 Planned interim analysis and data monitoring.................................................................96
14.8 Determination of sample size...........................................................................................96
15
ETHICS AND REGULATORY REQUIREMENTS......................................................97
15.1 Informed consent .............................................................................................................97
15.2 Subject identification cards..............................................................................................97
15.3 Institutional Review Boards and Independent Ethics Committees..................................97
15.4 Subject privacy.................................................................................................................98
15.5 Protocol amendments.......................................................................................................98
16
FINANCE, INSURANCE, AND PUBLICATION.........................................................99
17
REFERENCES ................................................................................................................99
18
APPENDICES ...............................................................................................................101
18.1 Quantitative Myasthenia Gravis Testing form...............................................................101
18.2 MG-Composite score.....................................................................................................105
18.3 MG muscle weakness PRO, Version 1..........................................................................106
18.4 Fatigue PRO, Version 1 .................................................................................................109
18.5 MG-Activities of Daily Living ......................................................................................112
18.6 MG Impairment Index - Patient Questionnaire and Manual..........................................113
18.7 MGFA classification......................................................................................................121
18.8 Suggested management guidelines for infusion reactions.............................................122
18.9 Diagnosis of anaphylactic reactions...............................................................................123
18.10
Headache Questionnaire ......................................................................................123
18.11
Tuberculosis Questionnaire .................................................................................127
18.12
Protocol Amendment 1 ........................................................................................128
18.13
Protocol Amendment 2 ........................................................................................171
19
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................193
20
SPONSOR DECLARATION ........................................................................................193
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LIST OF TABLES
Table 5.1:
Schedule of assessments ..................................................................................25
Table 6.1:
No-treatment periods for exclusionary immunosuppressants, biologics, 
and other therapies...........................................................................................37
Table 7.1:
Permitted concomitant treatments....................................................................43
Table 12.2:
Safety laboratory measurements......................................................................76
Table 12.3:
Required investigations and follow up for PDILI............................................79
Table 12.4:
PDILI laboratory measurements......................................................................82
Table 12.5:
PDILI information to be collected...................................................................83
Table 18.1:
Suggested management guidelines for infusion reactions.............................122
Table 18.2:
Headache Questionnaire ................................................................................123
LIST OF FIGURES
Figure 5.1:
Schematic diagram...........................................................................................31
Figure 18.1:
Quantitative Myasthenia Gravis Testing form...............................................101
Figure 18.2:
MG-Composite score.....................................................................................105
Figure 18.3:
MG muscle weakness PRO, Version 1..........................................................106
Figure 18.4:
Fatigue PRO, Version 1.................................................................................109
Figure 18.5:
MG-Activities of Daily Living ......................................................................112
Figure 18‒6:
MG Impairment Index – Patient Questionnaire.............................................113
Figure 18‒7:
MG Impairment Index – Examination Manual..............................................118
Figure 18‒8:
MG Impairment Index – Scoring Manual and Sheet.....................................119
Figure 18.9:
MGFA classification......................................................................................121
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LIST OF ABBREVIATIONS
 
ADL
activities of daily living
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
BAFF
B-cell activating factor
BP
blood pressure
CDMS
clinical data management system
CI
confidence interval
CPM
Clinical Project Manager
CRO
Contract Research Organization
C-SSRS
Columbia Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
DCP
Data Cleaning Plan
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic Case Report Form
ES
Enrolled Set
FAS
Full Analysis Set
Fc
crystalizable fragment
FcRn
neonatal Fc receptor for IgG
FV
Final Visit
FVC
forced vital capacity
GCP
Good Clinical Practice
GI
gastrointestinal
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GMP
Good Manufacturing Practice
HIV
human immunodeficiency virus
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
Ig
immunoglobulin 
IgA
immunoglobulin A
IgE
immunoglobulin E
IgG
immunoglobulin G
IGRA
interferon-gamma release assay  
IgM
immunoglobulin M
IMP
investigational medicinal product
IPI
interpotential interval
IRB
Institutional Review Board
IRT
interactive response technology
ITP
immune thrombocytopenic purpura
iv
intravenous
IVIg
intravenous immunoglobulin
LLOQ
lower limit of quantification 
LOCF
last observation carried forward
LS
least squares
LTBI
Latent tuberculosis infection
MCD
mean consecutive difference
MG
myasthenia gravis
MGADL
myasthenia gravis-Activities of Daily Living
MGFA
Myasthenia Gravis Foundation of America
MGII
Myasthenia Gravis Impairment Index
MMRM
mixed model repeated measures
miRNA
micro ribonucleic acid
mRNA
messenger ribonucleic acid
NMJ
neuromuscular junction
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NTMBI
non-tuberculosis mycobacterium infection
PD
pharmacodynamic(s)
PDILI
potential drug-induced liver injury 
PEOT
premature end of treatment
PK
pharmacokinetic(s)
PLEX
plasma exchange
PPS
Per-Protocol Set
PRO
patient-reported outcome
PS
Patient Safety
QMG
quantitative myasthenia gravis 
QTc
corrected QT interval
RNA
ribonucleic acid
RS
Randomized Set
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous
SD
standard deviation
SFEMG
single fiber electromyography
SOP
Standard Operating Procedure
SS
Safety Set
TB
tuberculosis
TEAE
Treatment-emergent adverse event
TNIP1
TNFAIP3-interacting protein 1
TST
Tuberculin skin test
ULN
upper limit of normal
USA
United States of America
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1
SUMMARY
The MG0002 study is a Phase 2a, multicenter, randomized, investigator- and subject-blind, 
placebo-controlled, 2-arm, repeat dose, treatment sequence study which will evaluate the
efficacy, safety, and tolerability of chronic-intermittent treatment with UCB7665 in subjects with 
moderate to severe generalized myasthenia gravis (MG). UCB7665 will be administered as 
subcutaneous (sc) doses of 4mg/kg or 7mg/kg, in subjects ≥18 years of age.
The study is planned to be conducted at approximately 30 sites in United States of America 
(USA), Canada, and Europe, with possible extension to other regions and countries. A total of 
42 subjects are planned to enter the Treatment Period in the study. The maximum study duration 
for an individual subject is approximately 18 weeks.
The study will consist of 3 Periods: Screening, Treatment, and Observation. After Screening, 
subjects will enter the Treatment Period, which will consist of Dosing Period 1 followed by
Dosing Period 2. Subjects will receive 3 doses of investigational medicinal product (IMP) at 
weekly intervals during each dosing period as follows:

Dosing Period 1 will be 4 weeks, with 2 parallel arms (UCB7665 7mg/kg or placebo).

Dosing Period 2 will be 2 weeks, with 2 parallel treatment arms (UCB7665 7mg/kg or 
UCB7665 4mg/kg).
The Observation Period will span 8 weeks after the final dose of UCB7665, with a Final Visit 
(FV) being scheduled at Visit 20. The sc infusions will last approximately 30 minutes, and 
subjects will be required to remain in the hospital/clinic at least 4 hours for safety monitoring 
after each infusion.
A Data Monitoring Committee (DMC) will be implemented as described in Section 14.7.
The primary efficacy variable will be the change from Baseline in Quantitative MG (QMG) 
score to Visit 9 (Day 29). The secondary efficacy variables will be the change from Baseline in 
MG-Composite score to Visit 9 (Day 29) and the change from Baseline in MG-Activities of 
Daily Living (MGADL) score to Visit 9 (Day 29). Other efficacy variables will be the following:
value and change from Baseline in QMG at each scheduled assessment during Treatment and 
Observation Periods; QMG responder (≥3.0 point improvement from Baseline) at each scheduled 
assessment during Treatment and Observation Periods; value and change from Baseline in 
MG-Composite score at each scheduled assessment during Treatment and Observation Periods; 
MG-Composite responder (≥3.0 point improvement from Baseline) at each scheduled assessment 
during Treatment and Observation Periods; value and change from Baseline in MGADL at each 
scheduled assessment during Treatment and Observation Periods; MGADL responder (≥3.0 
point improvement from Baseline) at each scheduled assessment during Treatment and 
Observation Periods; Myasthenia Gravis Foundation of America (MGFA) classification at each 
scheduled assessment during Treatment and Observation Periods; value and change from 
Baseline in MG muscle weakness severity, fatigue scales and Myasthenia Gravis Impairment 
Index (MGII) scores at each scheduled assessment during Treatment and Observation Periods; 
and change in mean consecutive difference (MCD) in jitter (single fiber electromyography
[SFEMG]) studies from Baseline to Visit 9 for the subjects consenting to this measurement at 
participating sites.
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following single- and repeat dose administrations by both intravenous (iv) and sc routes. 
UCB7665 mediated a clear dose- and exposure-related decrease in plasma IgG concentrations, 
achieving 45% to ≥70% decreased IgG concentrations at dose levels ranging from 5 to 30mg/kg 
in the absence of adverse effects. No consistent or dose-related effects of UCB7665 on albumin 
levels were observed in these studies.
To date, UCB7665 has been administered to human subjects in 2 clinical studies, UP0018 and 
TP0001. UP0018 is a completed first-in-human study in 49 healthy subjects. The study evaluated 
the safety, tolerability, PK, and the PD effect on total IgG levels of single ascending doses of iv 
and sc administered UCB7665. Doses of UCB7665 1, 4, and 7mg/kg were administered by both 
iv and sc routes in 3 cohorts, respectively, as an 1 hour infusion. The information from the study 
is summarized below.
Dose-dependent statistically significant reductions in levels of serum total IgG and 
dose-dependent reductions in levels of IgG subclasses (IgG 1 to 4) were observed after 
UCB7665 was administered by iv or sc routes. There were no deaths or serious adverse events
(SAEs) reported during the study, and no subjects discontinued the study due to TEAEs. 
UCB7665 was tolerated with an acceptable safety profile after the single administration of up to 
4mg/kg iv and up to 7mg/kg sc doses. For iv administration of UCB7665, the most frequently 
reported TEAEs were headache (10 subjects [55.6%]) and nasopharyngitis, nausea, pyrexia, and 
vomiting (each reported by 7 subjects [38.9%]). Four TEAEs with a maximum intensity of 
severe were reported in this study: headache (3 subjects [50.0%]) and back pain (1 subject 
[16.7%]); all of which were reported in the UCB7665 7mg/kg iv group. For sc administration of 
UCB7665, the most frequently reported TEAEs were headache (5 subjects [27.8%]) and back 
pain and diarrhea (each reported by 3 subjects [16.7%]). Importantly, there were fewer 
incidences of headaches and GI disturbances following sc administration of UCB7665 compared 
with iv administration. The safety profile of the sc route of administration, up to 7mg/kg of 
UCB7665, was considered to be manageable, and all subject reported TEAEs had a maximum
intensity of mild or moderate. The peak and total exposure of UCB7665 showed nonlinear 
increases consistent with target-mediated disposition. Based on the preliminary results, a 
minimal level of immunogenicity and minimal effects on 
 antibodies were 
observed. 
An ongoing study, TP0001, is a multicenter, open-label, single- and multiple-dose, multiple-arm 
Phase 2a study to evaluate the safety, tolerability, and efficacy of UCB7665 administered as sc 
doses in adult subjects with primary ITP. This ongoing study is the first study to evaluate 
multiple doses of UCB7665 and will evaluate multiple Treatment Groups of UCB7665. The dose 
arms are 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 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)
To date, 15 subjects in Dose Arm 1 (5x4mg/kg) and 13 subjects in Dose Arm 2 (3x7mg/kg) have 
safely completed his/her treatment period.  
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MG0002 will be the first study of the use of UCB7665 in MG. The aim of the study is to 
evaluate the efficacy, safety, and immunological effect of UCB7665, and to gather data for 
future study planning to fully evaluate the use of UCB7665 in MG.
For more detailed information, refer to the current version of the UCB7665 Investigator's 
Brochure.
3
STUDY OBJECTIVES
3.1
Primary objective
The primary objective of the study is:

To evaluate the clinical efficacy of UCB7665 as an chronic-intermittent treatment in subjects 
with generalized MG who are classified as moderate to severe 
3.2
Secondary objectives
The secondary objectives of the study are:

To gather data for future study planning, whether for chronic-intermittent treatment or a 
longer therapy option by evaluating the general concept that UCB7665 has a clinical effect in 
patients with generalized MG

To evaluate the safety and tolerability of UCB7665 administered by sc infusion in subjects 
with MG

To assess the effect of UCB7665 as measured by total IgG concentrations in serum
3.3
Exploratory objectives
The exploratory objectives are:

To assess the effect of UCB7665 on MG-specific autoantibodies (
 
 levels in serum

To evaluate the effects of UCB7665 on the concentration of IgG subclasses, immunoglobulin 
M (IgM), immunoglobulin A (IgA), and immunoglobulin E (IgE), and serum and plasma 
complement levels 

To evaluate the effect of UCB7665 on B-cell activating factor (BAFF) and on cytokines (in
all subjects)

To evaluate the effect of UCB7665 on cytokines in subjects experiencing infusion reactions

To evaluate the emergence of 
 with respect to immunogenicity and 
PK/PD

To evaluate the effect of UCB7665 on clinical electrophysiological parameters of 
neuromuscular transmission in a subset of subjects

To assess the plasma concentrations of UCB7665 administered by sc infusion 

To evaluate the effects of UCB7665 on blood biomarkers for safety (including, but not 
limited to 
,
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only in subjects with severe headache and/or moderate to severe GI 
disturbance

The effects of UCB7665 on 
 antibodies

To evaluate peripheral blood biomarkers in relation to disease etiology, progression and 
treatment outcome

To evaluate the genomic components of MG 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
Efficacy variables
4.1.1
Primary efficacy variable
The primary efficacy variable is:

Change from Baseline in QMG score to Visit 9 (Day 29)
4.1.2
Secondary efficacy variable
The secondary efficacy variables are:

Change from Baseline in MG-Composite score to Visit 9 (Day 29)

Change from Baseline in MGADL score to Visit 9 (Day 29)
4.1.3
Other efficacy variables
The other efficacy variables are:

Value and change from Baseline in QMG at each scheduled assessment during Treatment 
and Observation Periods

QMG responder (≥3.0 point improvement from Baseline) at each scheduled assessment 
during Treatment and Observation Periods

Value and change from Baseline in MG-Composite score at each scheduled assessment 
during Treatment and Observation Periods

MG-Composite responder (≥3.0 point improvement from Baseline) at each scheduled 
assessment during Treatment and Observation Periods

Value and change from Baseline in MGADL at each scheduled assessment during Treatment 
and Observation Periods

MGADL responder (≥3.0 point improvement from Baseline) at each scheduled assessment 
during Treatment and Observation Periods 

MGFA classification at each scheduled assessment during Treatment and Observation 
Periods

Value and change from Baseline in MG muscle weakness and fatigability at each scheduled 
assessment during Treatment and Observation Periods
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
Value and change (absolute and percentage) from Baseline in serum IgG subclass 
concentrations at each scheduled assessment during Treatment and Observation Periods

Change in MG-specific autoantibody
 levels in serum from Baseline 
at each scheduled assessment during Treatment and Observation Periods
4.2.4
Immunological variables
The other immunological variables are the following:

Change from Baseline in serum immunoglobulin (Ig) concentrations (total IgA, IgE, and 
IgM) at each scheduled assessment during Treatment and Observation Periods

Change from Baseline in serum complement levels (C3 and C4) and plasma complement 
levels (C3a and C5a) predose at Visit 2 and 4 hours postdose at each scheduled assessment 
during Treatment and Observation Periods

status (negative or confirmed positive) and either change 
from Baseline in relative mass units at each scheduled assessment during Treatment and 
Observation Periods or titre for those confirmed positive. 

Change from Baseline in serum BAFF levels

Change from Baseline in cytokines predose and postdose (postdose – in subjects 
experiencing infusion reactions) at assessments during Treatment and Observation Periods

Change from Baseline in 
antibodies

Change from Baseline in exploratory biomarkers relating to mechanism of action, disease 
activity, treatment response, and clinical outcome
5
STUDY DESIGN
5.1
Study description
This is a Phase 2a, multicenter, randomized, investigator- and subject-blind, placebo-controlled, 
2-arm, repeat dose, treatment sequence study evaluating the safety and efficacy of UCB7665 as 
an chronic-intermittent treatment for subjects with moderate to severe generalized MG.
Approximately 42 randomized subjects will be enrolled at approximately 30 sites from USA,
Canada, and Europe to achieve the targeted number of 40 evaluable subjects.
The maximum duration of the study per subject is approximately 18 weeks, consisting of a 
Screening Period (1 to 28 days), Treatment Period (6 weeks), and an Observation Period 
(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
form prior to the conduct of any study-related procedures. The use of concomitant medication 
while in the study will be discussed and subjects’ eligibility will be determined on the basis of 
the inclusion/exclusion criteria. The Screening Period should not exceed 28 days in total.
Treatment Period: The Treatment Period will consist of Dosing Period 1 followed by Dosing 
Period 2. Subjects will receive 3 doses of IMP at weekly intervals during each dosing period as 
follows.
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
Dosing Period 1 will be 4 weeks, with 2 parallel Treatment Groups (UCB7665 7mg/kg or 
placebo).

Dosing Period 2 will be 2 weeks, with 2 parallel Treatment Groups (UCB7665 7mg/kg or 
UCB7665 4mg/kg).
Prior to receiving an infusion with IMP, subjects will be assessed for efficacy measurements at 
each visit in the Treatment Period. For all safety and efficacy measurements, the order specified 
in the Study Procedures Manual is recommended to be used as a guide.
Dosing Period 1: Dosing Period 1 will last for approximately 4 weeks (Day 1 to Day 28) and 
includes Visits 2, 3, 4, 5, 6, 7, and 8. Following completion of the Screening Period, eligible 
subjects will check-in at the clinic/hospital for the Randomization Visit (Visit 2). Subjects who 
continue to meet eligibility requirements will be randomized 1:1 to receive 7mg/kg of UCB7665 
or placebo, administered by an approximately 30 minute sc infusion at weekly intervals for
3 weeks (Visits 2, 4, and 6) followed by an assessment visit at Week 4 (Visit 8). At Visits 2, 4, 
and 6 in Dosing Period 1, subjects will be required to remain in the clinic/hospital for at least
4 hours for safety monitoring after the infusion. Subjects may leave the clinic/hospital once the 
safety monitoring postdose period is over and the investigator or designee has no safety 
concerns. A follow-up telephone call will be conducted 24 hours postdose to assess the status of 
the subject (Visits 3, 5, and 7). Subjects will return to the clinic/hospital at Visit 8 for safety and 
efficacy assessments (see Section 5.2, Schedule of Study Assessments). The primary efficacy 
endpoint, change from Baseline in the QMG score, will be assessed at the beginning of Dosing 
Period 2 at Visit 9 (Day 29) prior to rerandomization. The efficacy assessments that are 
performed at Visit 9 will therefore occur 2 weeks after the final dose of study drug in Dosing 
Period 1.
Dosing Period 2: Dosing Period 2 will last for approximately 2 weeks (Day 29 to Day 43) and 
includes Visit 9, 10, 11, 12, 13, and 14. Subjects will return to the clinic for Visit 9, 11, and 13
for safety and efficacy assessments (see Section 5.2, Schedule of Assessments) in the order 
specified in Section 8. At Visit 9, following the administration of safety and efficacy 
assessments, subjects initially randomized at Baseline to placebo or to 7mg/kg of UCB7665 will 
be rerandomized 1:1 to receive either 3 doses of 7mg/kg or 3 doses of 4mg/kg administered by a 
30 minute sc infusion at weekly intervals (Visit 9, 11, and 13). The interactive response 
technology (IRT) will stratify the rerandomization based on the treatment received in Dosing 
Period 1 (see Section 7.10 for further details regarding randomization). At each weekly clinic 
visit in Dosing Period 2 (Visits 9, 11, and 13), subjects will be required to remain in the 
clinic/hospital for at least 4 hours safety monitoring postdose period as determined. Subjects may 
leave the clinic/hospital once the safety monitoring postdose period is over and the investigator 
or designee has no safety concerns. A follow-up telephone call will be conducted 24 hours 
postdose to assess the status of the subject (Visits 10, 12, and 14).
Observation Period: All subjects must be followed for 8 weeks after the final dose of IMP is 
administered. Subjects will return to the clinic for Visits 15, 16, 18, and 20 for efficacy and for 
safety assessments (see Section 5.2, Schedule of Assessments). Subjects will either return to the 
clinic/hospital, or, if possible and agreed by both investigator and subject, have home visits 
conducted by certified healthcare professionals, for Visits 17 and 19. The Observation Period 
begins the day after the final dose of IMP (ie, Visit 13, Day 43); Visit 15 (Day 50) is the first 
visit in the Observation Period.
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5.1.1
Exploratory genomic analyses
During this study, subjects will also have the option of providing additional informed consent for 
exploratory genomic (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.
If 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), at Visit 8, and prior to the last 
dose of IMP (Visit 13).
For RNA: Blood samples will be collected at Baseline (Visit 2), at Visit 4, at Visit 8, prior to the 
last dose of IMP (Visit 13), and at the FV (Visit 20).
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.
Any exploratory biomarker or genomic analysis will only ever be related to the exploration of 
the underlying causes of MG in patients, related biology, and drug response. Justification for 
additional genomic analyses is detailed in Section 5.4.3.
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.
5.1.2
Study duration per subject
The maximum duration of the study per subject will be approximately 18 weeks, consisting of 
the following 3 periods:
Screening Period: 1 to 28 days
Treatment Period: 6 weeks
Observation Period: 8 weeks
The end of the study is defined as the date of the final clinic/hospital or home visit of the final
subject in the study.
5.1.3
Planned number of subjects and sites
To ensure that at least 40 subjects are evaluable for the primary efficacy variables, a sample size 
of approximately 42 randomized subjects is planned at approximately 30 sites to achieve the 
targeted number of 40 evaluable subjects.
5.1.4
Anticipated regions and countries
It is planned to recruit subjects in USA, Canada, and Europe in this study, with possible 
extension to other regions and countries.
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5.2
Schedule of study assessments
Table 5.1 presents a summary of study assessments.
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Written informed consent
e
X
Written informed consent 
for genomic substudy
X
Demographic data
X
Verification of inclusion 
/exclusion criteria
X
X
Call or enter IRT to 
register the visit
X
X
X
X
X
X
Call or enter IRT/ 
Randomization
X
X
Withdrawal criteria
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
General medical/
procedures history
X
Prior and concomitant 
medication
X
X
X
X
X
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
Vital signsf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight, heightg
X
X
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Full physical 
examination
X
X
Brief physical 
examination
X
X
Full neurological 
examinationh
X
X
Brief neurological 
examination
X
X
Query for suicidalityi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECGj
X
X
X
X
X
X
X
X
X
X
X
Laboratory tests 
(hematology, chemistry, 
urinalysis)
X
X
X
X
X
X
X
X
X
X
X
X
Serology testing for HIV, 
Hepatitis B, and Hepatitis 
C
X
IGRA tuberculosis testk
X
Tuberculosis Signs and 
Symptoms questionnaire
X
X
Blood sampling for PK 
of UCB7665l
X
X
X
X
X
X
X
X
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
MGII 
X
X
X
X
X
X
X
MGFA classification 
X
X
X
X
Jitter (SFEMG)
measurementt
X
X
Headache questionnaireu
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Stool sample assessmentv
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interview
X
AE=adverse event; BAFF=B-cell activating factor; BL=Baseline; BP=blood pressure; CSF=cerebrospinal fluid; CT=computed tomography; DNA=deoxyribonucleic acid; 
ECG=electrocardiogram; FV=Final Visit; GI=gastrointestinal; HIV=human immunodeficiency virus; IgA=immunoglobulin A; IgE=immunoglobulin E; IgG=immunoglobulin G; 
IGRA= interferon-gamma release assay; IgM=immunoglobulin M; IMP=investigational medicinal product; IRT=interactive response technology; LP=lumbar puncture; 
MG=myasthenia gravis; MGADL=myasthenia gravis-Activities of Daily Living; MGFA=Myasthenia Gravis Foundation of America; MRI=magnetic resonance imaging; 
PEOT=premature end of treatment; PK=pharmacokinetics; PR=pulse rate; RNA=ribonucleic acid; QMG=Quantitative Myasthenia Gravis; 
 
B; SFEMG=single fiber electromyogram; TB=tuberculosis; UV=Unscheduled Visit
a Subjects will return to the clinic/hospital for Visits 15, 16, 18, and 20; for Visits 17 and 19 subjects will either return to the clinic/hospital, or, if possible and 
agreed by both the investigator and subject, have home visits conducted by certified healthcare professionals.
b This visit is a telephone contact 24 hours post-IMP dose start.
c Subjects who withdraw early will be encouraged to complete the PEOT Visit plus the FV (approximately 8 weeks after the final study drug administration).
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 Includes consent for jitter (SFEMG) for the subjects consenting to this measurement at the participating sites. Additional informed consent is needed for 
participation in the exploratory genomic substudy.
f Systolic and diastolic BP, pulse rate, temperature, and respiratory rate. On dosing days, vital signs will be measured prior to IMP administration, 15 minutes 
after the start of the infusion, at the end of the infusion, 2 hours after the end of infusion and 4 hours after the end of the infusion. At nondosing visits, vital 
signs need only be taken once during the visit.
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g Body weight at Screening and at Visit 9 will be used for calculation of dose; height will be assessed only at Screening.
h In addition to Screening and the FV, a full neurological examination should be performed for any subject who experiences severe headache.
i A query for suicidal ideation will be asked by Investigator at each clinical visit (including Visit 17 or Visit 19 when it is conducted at the clinic). A full 
Columbia Suicide Severity Rating Scale (C-SSRS) assessment will be performed only when subject has a positive response to the suicidal ideation query. If a 
subject has active suicidal ideation as confirmed by the answer ‘Yes’ to Question 4 or Question 5 of the C-SSRS assessments, the subject will be excluded or
withdrawn from the study and immediately referred to a Mental Healthcare Professional.
j ECGs will be read by a central reader.
k The IGRA test will be performed in a central laboratory. Subject should not be dosed until IGRA result is available and negative.
l Pre- and postdose at Visits 2, 4, 6, 9, 11, and 13; postdose samples are to be taken 4 hours after the infusion has ended.
m Blood sample to be taken prior to dosing of IMP.
n Urine pregnancy test will be performed using a dipstick test; a positive urine pregnancy test must be confirmed using a serum pregnancy test.
o Sampling will be performed predose at Visit 2 and 4 hours postdose at Visits 2, 4, 6, 9, 11 and 13. A sample will be obtained at Visit 20.  
p Sampling for exploratory safety biomarkers at Baseline (Visit 2) and 4 hours post dosing (Visit 2) for all subjects. During follow up only in subjects with severe 
headache and/or moderate to severe GI disturbances.
q Sampling will be performed pre- and 4 hours postdose at Visits 2, 6, 9 and 13. A sample will be obtained at Visit 20. Samples will be obtained at Visits 4 and 
11 for subjects with an infusion reaction.
r This assessment will be performed at the clinic/hospital. If the subject has a home visit with certified health professionals at Visit 17 and Visit 19, this 
assessment will not be performed.
s Subjects should not take pyridostigmine (or any 
[
inhibitor medication) from midnight before testing when medically safe to do so 
to standardize testing, but if not medically appropriate, then the treatment can be continued but the testing should be performed as best as possible at the same 
timeframe post last any 
 inhibitor dosing for each evaluation during the study.
u 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.
v 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.
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5.3
Schematic diagram
Figure 5.1 presents a schematic diagram of the study design.
Figure 5.1:
Schematic diagram
sc=subcutaneous
5.4
Rationale for study design and selection of dose
5.4.1
Choice of study design and endpoints
The primary objective of the study is to evaluate the clinical efficacy of UCB7665 as a
chronic-intermittent treatment for subjects with moderate to severe generalized MG. 
Additionally, this study will provide data for future study planning, whether for chronic-
intermittent treatment or a longer therapy option by evaluating the general concept that 
UCB7665 has a clinical effect in patients with generalized MG.
During the first Treatment Period, a 2-arm parallel design study will allow comparison of the 
change from Baseline in QMG score to Visit 9 (Day 29) between UCB7665 7mg/kg and placebo.
The choice of the primary efficacy outcome measures and the timing of approximately 4 weeks 
after the first dose of study drug are predicted to be the optimal approach to measure 
improvements based on effect seen in other therapies and recommendations of the Scientific 
Advisory Board of the MGFA (Barth 2013; Benatar 2012; Howard 2013). Then the second 
Dosing Period with a rerandomization allows for additional supportive data to be evaluated as 
well as offering the placebo subjects a chance to receive UCB7665.
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Each subject will be asked to participate up to a maximum of approximately 18 weeks, 
consisting of a Screening Period (14 to 28 days), Treatment Period (6 weeks) and an Observation 
Period (8 weeks). The Treatment Period will consist of Dosing Period 1 followed by Dosing 
Period 2. Dosing Period 1 will have 2 parallel Treatment Groups (UCB7665 7mg/kg or placebo) 
and last 4 weeks. Dosing Period 2 will have 2 parallel Treatment Groups (UCB7665 7mg/kg or 
UCB7665 4mg/kg) and last 3 weeks. Overall, this will result in 4 Treatment Groups:
Group 1: Subjects will receive 3 weekly doses of 7mg/kg in Dosing Period 1 followed by 
3 weekly doses of 7mg/kg in Dosing Period 2.
Group 2: Subjects will receive 3 weekly doses of 7mg/kg in Dosing Period 1 followed by 
3 weekly doses of 4mg/kg in Dosing Period 2.
Group 3: Subjects will receive 3 weekly doses of placebo in Dosing Period 1 followed by 
3 weekly doses of 7mg/kg in Dosing Period 2.
Group 4: Subjects will receive 3 weekly doses of placebo in Dosing Period 1 followed by 
3 weekly doses of 4mg/kg in Dosing Period 2.
All subjects participating in Dosing Period 2 will therefore receive UCB7665 treatment, and no 
subject will be treated with placebo for more than 4 weeks. The primary outcome measure, 
change from Baseline in QMG score compared to placebo at Visit 9, will be assessed for subjects 
treated with 7mg/kg UCB7665 vs subjects treated with placebo in Dosing Period 1. The 
comparison of the change from Baseline in QMG score at Visit 16 in Group 3 will strengthen 
analyses of the results of the primary outcome measure in Group 1. Because subjects in both 
Group 1 and 2 will be dosed for 6 times over 6 weeks, the data from these subjects will inform 
safety and the development of ADAs with extended dosing durations. Data regarding dose 
response and the time to clinical and PD response from Group 3 (7mg/kg) vs. Group 4 (4mg/kg) 
in the second Dosing Period will be able to be compared. Furthermore, safety and efficacy data 
from Group 2 in particular will provide information addressing the concept of treating subjects 
with a higher “loading” dose and then maintaining them on a lower dose regimen.
5.4.2
Rationale for dose selection
The dose and regimen of IMP to be used in the current study (UCB7665 7mg/kg sc) was selected 
based on the results from the first-in-human study UP0018. UP00018, a single ascending dose 
study in healthy subjects, explored the dose range of UCB7665 (between 1 and 7mg/kg) and 
characterized the PK and PD effect on total IgG. 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. UCB7665 was tolerated with an 
acceptable safety profile after the single administration of a 7mg/kg sc dose, and all 
subject-reported TEAEs had a maximum intensity of mild or moderate.
The dose-exposure-response relationship, with serum total IgG as primary endpoint, was 
determined using nonlinear 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 an IgG reduction of 70% or greater. The 
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model based simulations demonstrate that weekly doses of UCB7665 7mg/kg for 3 consecutive 
weeks are expected to produce maximum mean IgG reductions of >70%. Thus, exploratory 
comparisons of the 4mg/kg and 7mg/kg dosing regimens for treating adult subjects with 
moderate to severe generalized MG will be evaluated in the current study, MG0002.
5.4.3
Justification for additional genomic analyses
DNA analysis
Monozygotic MG twin concordance is estimated to be about 35% supporting the central role of 
environmental factors in MG etiology. MicroRNAs provide a mechanistic link between 
environmental and genetic risk factors in disease development, and are providing support for 
specific epigenetic mechanisms associated with MG. Genetic studies have mainly pointed at 
specific human leukocyte antigen alleles implicated in MG susceptibility, however recently both 
 and 
 
were indicated to be associated with MG in a genome wide association study.
Direct genetic and environmental/epigenetic influences are complex and require further 
elucidation to understand the cause, progression and potential treatment of MG. Through the 
collection of whole blood DNA from consenting subjects, this substudy will help enable further 
investigation of this complex disease, facilitate identification and characterization of genetic 
and/or epigenetic components of MG and will lead to important clues into the pathogenesis of 
MG 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, ITP, and MG. Such signatures have provided molecular insight into disease 
biology and activity and can facilitate patient stratification via gene expression panels predictive 
of therapeutic response and clinical outcomes.
MicroRNAs 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.
Collection of blood for RNA analysis will facilitate insight into the molecular etiology of MG at 
the genomic level and may enable identification of candidate markers for treatment effect and 
safety, and assessment of the feasibility of patient stratification.
In summary, the genetic, epigenetic, and genomic elements of MG require further elucidation to 
understand the cause, progression, and appropriate treatment of MG. 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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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.
2. Subject is ≥18 years of age at Visit 1 (Screening).
3. Subject has a well-documented diagnosis of MG at Visit 1 (Screening), based on subject 
history and supported by previous evaluations.
4. Subject would currently be considered for treatment with immunological therapy (eg
IVIG/PLEX) by the investigator.
5. Subject has a well-documented record of autoantibodies against 
 or 
prior to 
Visit 1 (Screening).
6. Female subjects of child bearing 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 
study drug 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 2 months after their final dose of study drug. 
According to the International Council for Harmonisation (ICH) M3 (R2), 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
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
Congenitally sterile
7. 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.
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria are met:
1. Subject has previously received treatment in this study or subject has previously been 
exposed to UCB7665.
2. Subject has participated in another study of an IMP (or a medical device) within the previous 
30 days of Screening or is currently participating in another study of an IMP (or a medical 
device).
3.
Subject has a known hypersensitivity to any components of the IMP.
4. Subject has a history of hyperprolinemia, since L-proline is a constituent of the UCB7665
IMP.
6.2.1
Exclusion criteria related to health status
5. Subjects with MG only affecting the ocular muscles.
6. Subjects with severe weakness affecting oropharyngeal or respiratory muscles, or who have 
myasthenic crisis at Screening or impending crisis.
7. Subject has QMG score of <11 at Baseline.
8. Subject has a serum total IgG level ≤6g/L at Screening.
9. Absolute neutrophil count <1500 cells/mm3.
10. Subject has any medical condition (acute or chronic illness) or psychiatric condition that, in 
the opinion of the investigator, could jeopardize or would compromise the subject’s ability to 
participate in this study.
11. Subject has any laboratory abnormality that, in the opinion of the investigator, is clinically 
significant, has not resolved at randomization, and could jeopardize or would compromise 
the subject’s ability to participate in this study.
12. Subject has 12-lead ECG with changes considered to be clinically significant upon medical 
review. The ECG contains findings that may represent a significant abnormality. The clinical 
significance of the findings needs to be assessed by the investigator to determine eligibility, 
and any queries regarding continuation of the subject must be addressed with the medical 
monitor.
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13. A screening glycosylated hemoglobin HbA1c value >8%, for subjects with known history of 
diabetes mellitus.
14. Subject has renal impairment, defined as:

Serum creatinine level of ≥1.4mg/dL for females and ≥1.5mg/dL for males at Screening 
Visit
15. Subject has >2x upper limit of normal (ULN) of any of the following: alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or 
>ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert’s syndrome). If 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 randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin
but <1.5xULN, 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, 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 (>2xULN) may 
be repeated once for confirmation. This includes rescreening.
16. Female subject who is pregnant or lactating.
17. Subject has planned an elective surgical procedure in the coming 6 months.
18. The subject is not considered reliable and capable of adhering to the protocol visit schedule, 
or medication intake according to the judgment of the investigator.
19. Subject has a history of chronic alcohol or drug abuse within the previous 12 months.
20. Subject has a clinically relevant active infection (eg, sepsis, pneumonia, or 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.
21. Subject has a history of clinically relevant ongoing chronic infections including but not 
limited to human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, or who tests 
positive for HIV, Hepatitis B, or Hepatitis C at the Screening Visit.
22. Subject has a family history (immediate family member) of primary immunodeficiency.
23. Subject has active neoplastic disease or history of neoplastic disease within 5 years of study
entry (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).
24. Subject has a history of a major organ transplant or hematopoietic stem cell/marrow 
transplant.
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6.2.2
Exclusion criteria related to concomitant medications/procedures
25. 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.
26. 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).
27. 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 
monitoring has shown they did not return to normal range.
28. Subject has been treated with immunosuppressants, biologics, and other therapies as detailed 
in the recent timeframe as detailed in Table 6.1 OR has not been on stable dosing regimens of 
the medications as detailed in Table 7.1.
29. Exclusion Criterion 29 was deleted per Protocol Amendment 1.
30. Subject had a thymectomy in the past 6 month or a thymoma at any time that required 
chemotherapy and/or radiotherapy.
Table 6.1:
No-treatment periods for exclusionary immunosuppressants, 
biologics, and other therapies
Generic name (commercial/trade names)
Period relative to Baseline Visit (regardless of 
route)
Immunosuppressants
Cyclophosphamide (Cytoxan®)
Pimecrolimus (Elidel®)
Vinca alkaloids (vincristine, vinblastine)
Biologics (mabs and fusion proteins)
Abatacept (CTLA 4-Ig) (Orencia®)
Belimumab (Benlysta™)
Golimumab (Simponi™)
Natalizumab (Tysabri®)
Ofatumumab (Arzerra)
Rituximab (Rituxan®) and ocrelizumab
TACI-Ig (Atacicept)
Veltuzumab
Other biologics
Others
Intravenous or subcutaneous immunoglobulin
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Generic name (commercial/trade names)
Period relative to Baseline Visit (regardless of 
route)
IPP-201101 (Lupuzor™)
PLEX (plasma exchange)
Immunoabsorption
6.2.3
Exclusion criteria related to other risks
31. Subject has a lifetime history of suicide attempt (including an 
 or has suicidal ideation in the past 6 months as indicated by a 
positive response (Yes) to either Question 4 or Question 5 of the Columbia-Suicide Severity 
Rating Scale (C-SSRS) at Screening.
32. Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or
latent tuberculosis infection (LTBI), 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. LTBI (see Section 12.3.1 for further details and instructions).
d. NTMBI is defined as a group of lung infections caused by mycobacteria different from 
mycobacterium tuberculosis infections.
6.3
Rescreening and Rechecking
Subjects with isolated results that are outside the specified ranges and that are deemed potentially 
clinically significant will be allowed to rescreen at the discretion of the investigator, following 
discussion with the sponsor’s medical monitor/study physician, if appropriate.
If a subject has 1 isolated test result outside the specific range which is deemed clinically 
nonsignificant, the abnormal value may be rechecked at the discretion of the investigator, 
following discussion with the sponsor’s 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.
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6.4
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care.
Subjects MUST be withdrawn from the study if any of the following events occur:
1. Subject withdraws his/her consent.
2. Subject becomes pregnant during the study, as confirmed by a positive pregnancy test.
Subjects MUST discontinue IMP if any of the following events occur:
1. 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 adverse event (AE) of GI disturbance or severe 
headache which is considered related to the IMP in the opinion of the investigator
(Section 12.1.10).
-
Subject has an AE of infusion reaction of severe intensity requiring corticosteroid 
and/or epinephrine therapy.
-
Subject has an AE of anaphylactic reaction requiring corticosteroid and/or 
epinephrine therapy.
-
Subject has a TB test that is confirmed positive or any further evidence suggestive of 
potential TB infection (eg, exposure) and further examinations result in a diagnosis of 
active TB or LTBI (refer to Section 12.3.1) for further details and instructions.
-
If an NTMBI is identified during a study, the same withdrawal procedures as those 
used for an active TB infection identified during the study should be followed.
2. The sponsor or a regulatory agency requests withdrawal of the subject.
3. Subject is treated with rescue therapy (refer to Section 7.8.3).
4. Subject received rituximab during the Treatment Period.
5. Subject received prohibited concomitant medications (as defined in Section 7.8.2 of this 
protocol) during the Treatment Period.
6. According to the investigator’s judgment this is in the best interest of the patient.
7. Meets criteria for liver injury (Section 6.4.1).
8. Subject has active suicidal ideation as indicated by a positive response (Yes) to either 
Question 4 or Question 5 of the “Since Last Visit” version of the C-SSRS. The subject 
should be referred immediately to a Mental Healthcare Professional.
Subjects MAY be withdrawn from the study at the discretion of investigator, medical monitor, 
and study physician if any of the following events occur:
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Subject is noncompliant with the study procedures or medications in the opinion of the 
investigator.
Subjects who withdraw from the study or discontinue IMP should complete the assessments 
outlined for the Premature End Of Treatment (PEOT) Visit (see Table 5.1 and Section 8.5). 
Subjects will be encouraged to return to the clinic/hospital to complete the Observation Period 
Visits and the FV (approximately 8 weeks after the final study drug administration).
Investigators should attempt to obtain information on subjects in the case of withdrawal.
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 IMP discontinuation and subject withdrawal, must be 
recorded in the source documents. The eCRF must document the primary reason for withdrawal 
or discontinuation, plus whether or not the blind was broken, with the reason and date for this.
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.
6.4.1
Potential drug-induced liver injury IMP discontinuation criteria
Subjects with potential drug-induced liver injury (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 study drug: 

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 study drug:

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 study 
drug administration after discussion with the responsible UCB physician, but only when the 
requirements for rechallenge with study drug as provided in Section 12.2.1.2.1 are followed.
The PDILI criterion below allows for subjects to continue on study drug 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 12.2.1. If subjects are unable to 
comply with the applicable monitoring schedule, IMP must be discontinued immediately.
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chronology of these events (infusion start and stop time) should be recorded accurately in the 
source data and eCRF, along with the volume infused, and the location of the infusion.
7.3
Packaging
The IMP will be manufactured, packaged, and labeled according to Good Manufacturing 
Practice (GMP) guidelines and applicable laws or regulations. The IMP will be suitably 
packaged in such a way as to protect it from deterioration during transport and storage.
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current ICH guidelines on Good 
Clinical Practice (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 according to the storage conditions mentioned on the label.
Appropriate storage conditions must be ensured either by controlling the temperature (eg, room, 
refrigeration unit) or by completion of a temperature log in accordance with local requirements 
on a regular basis (ie, every workday), showing actual and minimum/maximum temperatures 
reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual.
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, damaged (due to breakage or wastage), not used, partially 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), partially used, unused, damaged, and/or expired IMP must be reconciled and either 
destroyed at the site according to local laws, regulations, and UCB Standard Operating 
Procedure (SOPs), or returned to UCB (or designee). Investigational medicinal product intended 
for the study cannot be used for any other purpose than that described in this protocol.
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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 concomitant medication
Table 7.1 lists the concomitant medications that are permitted during the course of the study at a 
stable dose.
Table 7.1:
Permitted concomitant treatments
Permitted 
Medications
Dose
Comment
Oral Corticosteroids 
(eg, prednisolone)
-
Methotrexate
≤30mg/week
Mycophenolate mofetil
≤3g/day
Cyclosporina
≤5mg/kg/day for 
unmodified
≤4mg/kg/day for modified 
(microemulsion)
Azathioprine
≤3mg/kg/day
Cholinesterase 
inhibitors
≤600mg 
Pyridostigmine/day
Tacrolimusb
≤5mg/day
a Doses higher than listed are permissible if trough level is ≤300ng/L.
b If the total daily weight-based dose is >5mg, then a plasma trough level should be checked to 
ensure subject is not above the recommended therapeutic range.
Subjects should not take pyridostigmine (or any 
) from 
midnight before testing when medically safe to do so to standardize testing, but if not medically 
appropriate, then the treatment can be continued but the testing should be performed as best as 
possible at the same timeframe post any last 
 
 medication inhibitor 
dosing for each evaluation during the study.
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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.
7.8.2
Prohibited concomitant treatments (medications and therapies)
The following concomitant medications and therapies are prohibited during the study:

IVIg

All biologics including rituximab

Cyclophosphamide

Pimecrolimus

IPP-201101 (Lupuzor™)

PLEX 

Immunoadsorption

Medications which could interfere with the function of the NMJ (and which therefore could 
impair subjects with MG), such as, but not limited to, the following medications. For a more 
detailed list please refer to the MGFA medication list 
(http://www.myasthenia.org/LivingwithMG/DrugstoAvoid.aspx).

botulinum toxin

aminoglycoside antibiotics 

tetracycline antibiotics 

penicillamine 
If a subject needs or takes any prohibited medication or therapy (except IVIg, PLEX, or 
rituximab), the investigator will (where possible) discuss with the sponsor study physician and a 
decision will be made whether the subject can continue in the study or must be withdrawn. If the 
subject is treated with IVIg, rituximab, or PLEX, the subject must be withdrawn from the IMP,
but should be encouraged to continue with Observation Period Visits.
For subjects who require a medical or surgical procedure that requires the use of general 
anesthesia, discussion must occur prior to the procedure with the medical monitor or study 
physician. In an emergency situation, discussion should occur as soon as possible after the 
procedure, such that a decision on the subject’s continued participation in the study can be made.
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 Ig levels return to 
within the normal range.
If, during the Treatment and Observation Period, in the opinion of the investigator, a subject has 
a significant deterioration in clinical condition, then rescue therapy such as IVIg or PLEX should 
be considered.
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by the investigator must be recorded in the source documents and on the Study Termination 
eCRF page.
Inadvertent unblinding has to be listed as a major protocol deviation.
7.10
Randomization and numbering of subjects
An IRT will be used for assigning eligible subjects to the different treatment regimens (as 
applicable) based on a predetermined production randomization and/or packaging schedule. The 
1:1 randomization schedules will be produced by the IRT vendor. The IRT vendor will also 
generate lists of IMP, as appropriate, according to the visit schedule, the Treatment Group and 
the subject’s weight.
To enroll a subject (Visit 1), the investigator or designee will contact the IRT and provide brief 
details about the subject to be screened. 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 IRT regarding a 
particular subject. Subject numbers and kit numbers will be tracked via the IRT.
To enroll a subject in Dosing Period 1, the investigator or designee will contact the IRT and 
provide brief details about the subject to be randomized. The IRT will allocate kit numbers to the 
subject based on the randomization number.
To enroll a subject in Dosing Period 2, the investigator or designee will again contact the IRT 
and provide the subject’s screening number and weight at Visit 9. The subject will be 
rerandomized in a 1:1 ratio to receive one of the two doses of UCB7665. The IRT will stratify 
the rerandomization based on the treatment received in Dosing Period 1. At this rerandomization, 
the subject will receive a second randomization number which, as in Dosing Period 1, will be 
used by the IRT to allocate appropriate kit numbers.
8
STUDY PROCEDURES BY VISIT 
A detailed schedule of study procedures is provided in Table 5.1.
For details of the standard safety hematology, clinical chemistry, and urinalysis, see Table 12.2.
8.1
Screening Period
8.1.1
Visit 1 (Day -28 to -1) Screening Visit 
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 genomic (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 MG0002:
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
Obtain written informed consent 

Obtain optional informed consent for genomic substudy 

Demographic data (includes date of birth, gender, and race/ethnicity)

Verification of inclusion/exclusion criteria

General medical history and medical procedures history (including history of tetanus 
immunization)

Prior and concomitant medications

Vital signs (systolic and diastolic BP, pulse rate, temperature, and respiratory rate)

Body weight and height

Recording of AEs

Physical examination (Full)

Neurological examination (Full)

Assessment of MG status:

MG-composite scale

QMG scale

MGFA classification

Query for suicidality (Screening)
If positive response (Yes), a full C-SSRS will be performed.

12-lead ECG

Blood samples:

Standard safety laboratory tests: hematology and clinical chemistry, plus serology testing 
for HIV, Hepatitis B, and Hepatitis C

Immunoglobulins (Total IgG and subclasses)

Vaccination-specific antibody titers (
)

Serum pregnancy test for women of childbearing potential

Tuberculosis assessments:

IGRA

Tuberculosis Sign and Symptoms questionnaire

Standard safety urinalysis 

Call or enter IRT to register the visit
8.2
Dosing Period 1
In Dosing Period 1, visits will be performed at weekly intervals. 
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8.2.1
Visit 2 (Day 1, Baseline)
Visit 2 can occur at any time after Visit 1, but no later than 28 days after Visit 1. Eligible 
subjects will be randomized at Visit 2 and the first dose of IMP (UCB7665 7mg/kg sc infusion) 
or placebo will be administered as per the subject’s randomization.
The following assessments and procedures will be performed at this visit:
Predose:

Verification of inclusion/exclusion criteria

Withdrawal criteria

Prior and concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic BP, pulse rate, temperature, and respiratory rate)

Recording of AEs

Physical examination (brief)

Neurological examination (brief)

Assessment of MG status:

MG-composite scale

QMG scale

Muscle weakness severity and fatigability scale

Fatigue scale

MGADL scale

MGII

MGFA classification

Query for suicidality (since last visit):
If positive response (Yes), a full C-SSRS will be performed.

12-lead ECG

Blood samples:

Standard safety laboratories: hematology and clinical chemistry

PK of UCB7665 


Serum complement (C3,C4) and plasma complement levels (C3a and C5a)

Ig (total IgG and subclasses)

IgA, IgM, and IgE
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
Recording of AEs

Headache questionnaire if required

Stool sample assessment if required

Blood samples 

Serum complement (C3,C4) and plasma complement levels (C3a and C5a)

PK of UCB7665

Cytokines should be collected if infusion reaction occurs
8.2.4
Visit 5 (Day 9)
The subject will be contacted by telephone for collection of prior and concomitant medications, 
AEs, and withdrawal criteria data. Headache questionnaire will be completed if required. This 
visit should occur 24 hours after the IMP dose started.
8.2.5
Visit 6 (Day 15)
The following assessments and procedures will be performed at this visit:
Predose: 

Withdrawal criteria

Prior and concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic BP, pulse rate, temperature, and respiratory rate)

Recording of AEs

Assessment of MG status:

MG-composite scale

QMG scale

Muscle weakness severity and fatigability scale

Fatigue scale

MGII

Query for suicidality (since last visit):
If positive response (Yes), a full C-SSRS will be performed.

12-lead ECG

Blood samples:

Standard safety laboratories: hematology and clinical chemistry

PK of UCB7665

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
Cytokines

Standard safety urinalysis 

Urine pregnancy test for women of childbearing potential

Call or enter to IRT/Rerandomization

Jitter (SFEMG) measurement
During dosing of IMP: 

IMP administration

Vital signs (systolic and diastolic BP, pulse rate, temperature, and respiratory rate)

Recording of AEs
Postdose:

Recording of AEs

Headache questionnaire if required

Stool sample assessment if required

Blood samples 

Serum complement (C3,C4) and plasma complement levels (C3a and C5a)

PK of UCB7665

Cytokines
8.3.2
Visit 10 (Day 30)
The subject will be contacted by telephone for collection of prior and concomitant medications, 
AEs, and withdrawal criteria data. Headache questionnaire will be completed if required. This 
visit should occur 24 hours after the IMP dose started.
8.3.3
Visit 11 (Day 36)
The following assessments and procedures will be performed at this visit:
Predose: 

Withdrawal criteria

Prior and concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic BP, pulse rate, temperature, and respiratory rate)

Recording of AEs

Assessment of MG status:

MG-composite scale

QMG scale
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
Collection of whole blood for exploratory genomic (DNA and RNA) analyses

Standard safety urinalysis

Urine pregnancy test for women of childbearing potential

Call or enter IRT to register the visit

Administration of IMP 
During dosing of IMP: 

IMP administration

Vital signs (systolic and diastolic BP, pulse rate, temperature, and respiratory rate)

Recording of AEs
Postdose:

Recording of AEs

Headache questionnaire if required

Stool sample assessment if required

Blood samples 

Serum complement (C3,C4) and plasma complement levels (C3a and C5a)

PK of UCB7665

Cytokines 
8.3.6
Visit 14 (Day 44)
The subject will be contacted by telephone for collection of prior and concomitant medications, 
AEs, and withdrawal criteria data. Headache questionnaire will be completed if required. This 
visit should occur 24 hours after the IMP dose started.
8.4
Observation Period
During the Observation Period, visits will be performed at weekly intervals, apart from between 
Visits 17, 18, and 19, when visits will be performed at 2 weekly intervals. Subjects will return to 
the clinic for Visits 15, 16, 18, and 20 for efficacy and for safety assessments. Subjects will 
either return to the clinic, or, if possible and agreed by both the investigator and the subject, have 
home visits conducted by certified healthcare professionals, for Visits 17 and 19. No IMP will be 
administered in the Observation Period.
8.4.1
Visit 15 (Day 50)
The following assessments and procedures will be performed at this visit:

Assessment of withdrawal criteria

Prior and concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic BP, pulse rate, temperature, and respiratory rate)
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
BAFF

Urine pregnancy test for women of childbearing potential
8.4.6
Visit 20 (Day 99, Final Visit) and Premature End of Treatment Visit
Subjects who withdraw from the study drug will be encouraged to return to the clinic to complete 
a PEOT Visit and an FV approximately 8 weeks after the final dose of study drug. The following 
assessments and procedures will be performed at the FV (and PEOT Visit if applicable):

Prior and concomitant medications

Concomitant medical procedures

Vital signs (systolic and diastolic BP, pulse rate, temperature, and respiratory rate)

Body weight

Recording of AEs

Headache questionnaire if required

Tuberculosis Sign and Symptoms questionnaire

Stool sample assessment if required

Physical examination (full)

Neurological examination (full)

Assessment of MG status:

MG-composite scale

QMG scale

Muscle weakness severity and fatigability scale

Fatigue scale

MGADL scale

MGII

MGFA classification

Query for suicidality (since last visit):
If positive response (Yes), a full C-SSRS will be performed.

12-lead ECG

Blood samples:

Standard safety laboratories: hematology and clinical chemistry


Serum complement (C3,C4) and plasma complement levels (C3a and C5a)

Ig (total IgG and subclasses)
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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
Quantitative Myasthenia Gravis scale
For assessment of the QMG scale, investigators will follow the MGFA’s QMG Manual
instructions (see Section 18.1). Clinical personnel must complete mandatory training and be 
certified to assess subjects’ QMG score (details are provided in the Study Procedures Manual). 
Subjects should not take pyridostigmine (or any 
inhibitor medication) from midnight
before testing when medically safe to do so to standardize testing, but if not medically 
appropriate, then the treatment can be continued but the testing should be performed as best as 
possible at the same timeframe post last 
 inhibitor dosing for each evaluation during the 
study. The scale tests 13 items, including ocular and facial involvement, swallowing, speech, 
limb strength, and forced vital capacity (FVC). For the assessment of FVC, the same spirometer 
should be used each time a subject is tested, and if possible, the same person should carry out the 
assessment. Parameters and normal values for FVC will be decided between the study sites, such
that all sites are using the same information. The QMG is a validated assessment (Barnett et al, 
2012), with a higher score indicating more severe disease. Scoring for each item ranges from no 
weakness (0) to severe weakness (3), with an overall score range from 0 to 39. A 3 point change 
in the total score is considered clinically relevant. The test takes approximately 30 minutes to 
perform.
9.2
MG-Composite scale
For assessment of the MG-Composite scale, the investigator will examine the subject to score all 
items, except for talking, chewing, and swallowing for which the subject will self-assess. The 
MG-Composite scale is a validated assessment (Burns et al, 2010), with a higher score indicating 
more severe disease (see Section 18.2) and a 3-point change being of clinical relevance. The 
scale tests 10 items, with individual items being weighted differently. The overall score ranges 
from 0 to 50. Clinical personnel must complete mandatory training and be certified to assess 
subjects’ MG-Composite score (details are provided in the Study Procedures Manual).
9.3
Patient-reported outcomes
Subjects will complete 4 patient-reported outcomes (PROs) and participate in 1 subject exit 
interview as per time points mentioned in the schedule of study assessments in Section 5.2. 
Study personnel other than the treating physician should administer the PROs. The PROs should 
be completed by the subject themselves in a quiet place.
The PROs and the subject exit interview should be completed in the following order: MG muscle 
weakness and fatigability, Fatigue, MGADL and MGII, followed by the subject exit interview 
(which will be performed only at the FV). The PROs should only be checked for completeness. 
On dosing days, the PROs will be completed prior to dosing.
9.3.1
MG muscle weakness and fatigability
The MG muscle weakness and fatigability instrument (Appendix 18.3) consists of 27 items 
across 2 domains: 18 muscle weakness severity items and 9 symptom fatigability items. The 
subject will be asked to choose the response option that best describes the severity of muscle 
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weakness symptoms over the past 7 days using a 6-point Likert scale (“none” to “very severe”) 
and how frequently they experienced symptom fatigability over the past 7 days using a 5-point 
Likert scale (“none of the time” to “all of the time”), respectively. The muscle weakness score 
ranges from 0 to 90; the fatigability score ranges from 0 to 36. The overall score ranges from 0 to
126, with a higher result indicating more severe muscle weakness and fatigability.
9.3.2
Fatigue
The fatigue instrument (Appendix 18.4) consists of 55 items across 3 domains: 16 physical 
domain items (with a scale of 16 to 80), 18 mental domain items (with a scale of 18 to 90), and 
21 fatigability domain items (with a scale of 21 to 105). The subject will be asked to score each 
item based on how frequently she/he experienced the item during the past 7 days using a 5-point 
Likert scale (“none of the time” to “all of the time”). The overall score ranges from 55 to 275, 
with a higher result indicating more severe fatigue.
9.3.3
MG-Activities of Daily Living 
The MGADL is an 8-item PRO instrument developed on the basis of the QMG (Wolfe et al,
1999) (Appendix 18.5). The MGADL targets symptoms and disability across ocular, bulbar, 
respiratory, and axial symptoms. In a recent study, reliability, validity, and responsiveness of the 
MGADL were further assessed. The questionnaire showed strong construct validity when 
evaluated against the MG-Composite as well as against the MG-QOL15, high test retest 
reliability in a 1 week interval, and it was demonstrated that a 2-point improvement indicates 
clinical improvement (Muppidi, 2012; Muppidi et al, 2011). The total MGADL score ranges 
from 0 to 24, with a higher score indicating more disability. Subjects will complete the MGADL 
by themselves as described in the standardized administration of PROs.
9.3.4
Myasthenia Gravis Impairment Index
The MGII is a measure of disease severity based on the signs and symptoms of Myasthenia 
Gravis patients (Appendix 18.6). It was developed using a patient-centered approach and 
following current guidelines for outcome measure development, incorporating patient input 
throughout the different development phases (Barnett et al, 2014, Barnett et al, 2016). The MGII 
has 22 patient-reported and 6 examination items, and scores are presented as a sum of all items 
for a total score but also as an ocular and generalized sub-score.
The MGII has shown construct validity and reliability in an outpatient setting. It has less floor 
effect compared to other commonly used outcome measures, and it can effectively discriminate 
among patients with different degrees of severity (Barnett et al, 2016). Finally, the MGII is 
sensitive to detect clinical change after interventions, and most importantly it can detect patient-
meaningful change. Additionally, the MGII showed more relative efficiency than the QMGS, 
MGC and MG-ADL to detect change in short-term interventions for Myasthenia. Estimates for 
the minimal important difference were developed.
9.4
MGFA classification
The investigator will classify the subject’s MG using the MGFA Clinical Classification 
(Section 18.6) (Jaretzki et al, 2000). This is a 5 stage classification (I to V), with a higher class
indicating more severe disease.
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9.5
Jitter (Single Fiber Electromyography)
At participating sites, subjects consenting to jitter (SFEMG) measurement should not take 
pyridostigmine from midnight before testing when medically safe to do so to standardize testing, 
but if not medically appropriate, then the treatment can be continued but the testing should be 
performed as best as possible at the same timeframe post last 
 inhibitor dosing for each 
evaluation during the study. If pyridostigmine is taken, the time must be documented. This 
measurement will be performed by adequately trained and equipped investigators. Jitter 
measurements may be performed with a single-fiber EMG (SFEMG) electrode having a side-
ported recording surface with a 25μm diameter, or a disposable concentric needle electrode. This 
enables the measurement of fiber density and neuromuscular jitter (SFEMG) (which is a 
sensitive measurement of transmission across the NMJ) (Sanders, 2014). Jitter (SFEMG) can 
assist in demonstrating MG-associated abnormalities. In well treated MG, the jitter (SFEMG)
displays a more normal profile.
Details of the jitter (SFEMG) performance will be described in the jitter (SFEMG) measurement 
manual.
9.6
Subject exit interview
At the FV, qualitative interviews will be conducted by a study nurse/study personnel using a 
semi-structured interview guide. The aim of the interview is to collect the subject's experience 
with MG in terms of symptoms and impact on daily activities, and the perceived changes during 
the course of the study. The extent to which the exploratory PRO items and scales used fully 
captured their experience will also be assessed. The interviews will be audio-recorded. If a 
subject leaves the study prematurely, he/she will also be invited to participate in an exit interview 
at the PEOT Visit.
10
ASSESSMENT OF PHARMACOKINETIC/ 
PHARMACODYNAMIC/PHARMACOGENOMIC VARIABLES
10.1
Pharmacokinetic variable
The plasma concentration of UCB7665 will be characterized. Blood samples will be drawn 
according to the schedule of study assessments (Section 5.2).
Blood samples will be collected pre- and post- UCB7665 dosing. Additional blood will be drawn 
at the predose sampling for standard clinical laboratory tests. Postdose samples will be taken 
4 hours after the infusion has ended. At Visits 8 and 15, when no IMP is administered, blood for 
PK analysis will also be taken. 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 by qualified site personnel at the same 
time that samples are collected for standard clinical laboratory assessments. At dosing visits, 
these samples will be collected predose. Blood samples for PD analysis 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.
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12
ASSESSMENT OF SAFETY
12.1
Adverse events
12.1.1
Definitions
12.1.1.1
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 
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.
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.
12.1.1.2
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

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, but are not limited to, potential Hy’s Law [see 
Section 12.1.1.3], 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
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(A patient admitted to a clinic/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 clinic/hospital would also qualify for the initial inpatient hospitalization 
criteria. However, emergency room visits that do not result in admission to the clinic/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.)
12.1.1.2.1
Anticipated serious adverse events
Myasthenic crisis is anticipated to occur in the population studied in this protocol at some 
frequency that is independent of drug exposure.
This information does not change the investigator’s obligation to report all SAEs (including 
Anticipated SAEs) as detailed in Section 12.1.2.3.
12.1.1.3
Adverse events of special interest
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total 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.
12.1.1.4
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
12.1.1.5
Immediate reporting of adverse events
The following AEs must be reported immediately using the SAE Report Form according to the 
procedure in Section 12.1.2.3:
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
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 12.1.1.3)

AE of interest (see Section 12.1.1.4)

Confirmed LTBI, active TB, and NTMBI (see Section 12.3.1)
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)?”
12.1.2.1
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. Any discrepancies between the subject’s own words 
and the corresponding medical terminology should be clarified in the source documentation.
For recording an AE, Common Terminology Criteria for Adverse Events (CTCAE) will be used, 
and only if it is impossible to assess severity using CTCAE, then AE intensity will be used, 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 eCRF Completion Guidelines.
12.1.2.2
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
12.1.2.3
Additional 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.
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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 
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.
12.1.3
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. This follow-up 
requirement applies to AEs, SAEs, and AEs of special interest; further details regarding follow 
up of PDILI events is provided in Section 12.2.1.4.
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.
Information on SAEs obtained after clinical database lock will be captured through the PS 
database without limitation of time.
12.1.4
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 PS department by providing the completed 
Pregnancy Report and Outcome form (for contact details see SAE 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 a PEOT Visit.

The subject should immediately stop the intake of the IMP or be down-titrated as instructed 
at the PEOT Visit.
The investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
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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 needs 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/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 SAE 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 an 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.
12.1.5
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 eCRF, 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.
12.1.6
Suicidality
At screening, the Investigator will query each subject if he/she has a lifetime history of suicide 
attempt (including an 
 or suicidal ideation 
in the past 6 months. A full C-SSRS “Lifetime recent” assessment will be performed only when
the subject has a positive response to this query. This scale will be assessed by trained study 
personnel. When suicide attempt or suicidal ideation is confirmed by a positive response (Yes) to 
either Question 4 or Question 5 of the C-SSRS, the subject must be excluded and immediately 
referred to a Mental Healthcare Professional.
At each clinical visit, the investigator must query the suicidal ideation since the last visit. A full 
C-SSRS “Since last visit” assessment will be performed only when the subject has a positive 
response to this query. When suicide attempt or suicidal ideation is confirmed by a positive 
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response (Yes) to either Question 4 or Question 5 of the C-SSRS, the subject must be withdrawn 
and immediately referred to a Mental Healthcare Professional. The details of C-SSRS will be 
provided in the Study Procedures Manual.
12.1.7
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in 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).
12.1.8
Safety signal detection
An unblinded DMC will oversee at least 1 interim analysis during the course of the study during 
which the safety of UCB7665 will be assessed. The safety variables to be used and the decision 
rules will be specified in the DMC charter. Further details of these interim analyses are given in 
Section 14.7.
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 sponsor 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.
12.1.9
Hypersensitivity and adverse reactions
In the event of a severe infusion or anaphylactic reaction requiring corticosteroid and/or 
epinephrine therapy, the subject must permanently discontinue IMP and be managed as 
described in Section 18.8.
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.
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.
Moderate or severe anaphylactic reactions should be diagnosed using Sampson’s Criteria 
(Sampson et al, 2006) as described in Section 18.9. In the event of an anaphylactic reaction the 
infusion must be discontinued immediately and appropriate emergency resuscitation measures 
implemented.
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12.1.10
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 refers to bathing, dressing and undressing, 
feeding self, using the toilet, and 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 (if indicated) at the 
discretion of the investigator and may include, eg, a computed tomography scan, magnetic 
resonance imaging and/or a lumbar puncture for cerebral spinal fluid collection. In addition, 
assessment of exploratory safety biomarkers should be performed for subjects experiencing 
severe headache. 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 12.3.6. The 
Headache Questionnaire is available in Section 18.10.
12.1.11
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. In addition, collection of blood 
samples for assessment of exploratory safety biomarkers is required for subjects with moderate 
to severe GI disturbances including diarrhea.
Treatment of diarrhea will be provided as clinically indicated according to the local guidelines.
12.2
Laboratory measurements
Blood and urine specimens for routine assay of hematology, clinical chemistry, and urinalysis 
testing, and as well as serum and urine pregnancy 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 the urine pregnancy test prior to each dose. Specific details regarding the handling 
and processing of the serum chemistry, hematology, and urinalysis samples are provided in the 
study laboratory manuals.
Table 12.2 lists the laboratory parameters that will be measured.
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Table 12.2:
Safety laboratory measurements
Hematology
Chemistry
Urinalysis
Pregnancy test
Hematocrit
Electrolytes (calcium, 
phosphate, sodium, 
potassium, chloride, 
and magnesium)
Albumin
Urine HCG
Hemoglobin
Protein
Serum HCG
a
Platelet count
Nitrite
RBC count
ALP
Glucose
WBC count 
(including 
differential)
AST
pH
ALT
Leukocytes
HbA1cb
GGT
Blood
Total and direct 
bilirubin
Bilirubin
Serology
c
Urobilinogen
HBsAg
LDH
Ketone
HCV Ab
Total cholesterol
Creatinine
HIV (anti-HIV1 or
anti-HIV2 antibodies)
LDL - cholesterol
HDL – cholesterol, 
triglycerides
Tuberculosis
d
Amylase
Exploratory Safety 
Biomarkers
e
Creatine kinase
Creatinine
Total protein
Albumin
alpha- and beta–
globulins
Urea-N
Procalcitonin
hsCRP
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma 
glutamyltransferase; HbA1c=hemoglobin A1c; HBsAG=hepatitis B surface antigen; HCG=human chorionic 
gonadotropin; HCV Ab=hepatitis C virus antibody; HDL=high density lipoprotein; HIV=human immunodeficiency 
virus; hsCRP=high-sensitivity C-reactive protein; LDH=lactate dehydrogenase; LDL=low density lipoprotein; 
RBC=red blood cell; 
 B; WBC=white blood cell
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a Serum pregnancy testing is only performed at Visit 1 and, in the event of a positive pregnancy test, to confirm the 
results of a urine test
b HbA1c is performed at Screening only
c This serology performed at Screening only
d Interferon-gamma release assay by central laboratory.
e May include but not limited to the following biomarkers listed below. Samples collected for exploratory 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 the subject experienced a severe headache and/or moderate to severe GI disturbance.
12.2.1
Evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 6.4.1, 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 12.1.1.3), and, if applicable, also reported as an 
SAE (see Section 12.1.1.2).
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 12.2.1.1). 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 12.2.1.4).
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 eCRF 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 6.4.1), 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 12.2.1.2.1 are met, rechallenge with IMP may be appropriate.
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Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Table 12.3 below summarizes the approach to investigate PDILI.
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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
≥2xULNb
NA
Hepatology consult.c
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 12.2.1.3); 
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 12.2.1.2).  
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 12.2.1.3).
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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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 12.2.1.1. 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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12.2.1.1
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 or 
gastroenterologist. 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 12.2.1.3) and SAE report (if applicable).
12.2.1.2
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 6.4.1 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.
12.2.1.2.1
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 6.4.1 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 12.2.1.3 and
Section 12.2.1.4 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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12.2.1.3
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 eCRF. If the medical history of the subject indicates a requirement for other 
assessments not included below, these additional assessments 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 measurements detailed in Table 12.4 are to be assessed.
Table 12.4:
PDILI laboratory measurements
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain heterophile 
antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screen
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation
Additional
Prothrombin time/INRa
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; 
HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate 
dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; 
ULN=upper limit of normal
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a Measured only for subjects with ALT >8xULN, 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 addition information listed in Table 12.5 is to be collected:
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
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
12.2.1.4
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.
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12.3
Other safety measurements
12.3.1
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 risk of new or activation of 
LTBI, 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 the risk of TB 
infection in this study (see Section 6.2.3 [Exclusion Criterion 32] and Section 6.4 [Withdrawal 
Criteria 1]). Following are the key considerations of these procedures:
TB Tests at Screening
IGRA and TB questionnaire are required as indicated in Schedule of Assessments (Table 5.1).

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 must
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 Period.

In addition to IGRA test, 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 
Screening. See the ‘TB signs and symptoms questionnaire’ section for further instructions on 
using the questionnaire. Subjects with known TB, at a high risk of acquiring TB or with 
LTBI should be excluded from this study as described in Exclusion Criteria.
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 LTBI and active TB according to the local medical practice guidelines.
Subjects with confirmed LTBI or active TB or NTMBI will be immediately withdrawn from the 
study as described in Withdrawal Criteria. Confirmed LTBI, 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 to the Sponsor within 
24 hours of awareness.
Once withdrawn from study treatment, subjects should return for the PEOT, complete all early 
withdrawal assessments, and complete the follow-up visits.
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12.3.3
Vital signs
Vital signs will be measured at all visits as indicated in the schedule of study assessments 
(Table 5.1).
Vital signs to be assessed are as follows:

Pulse rate

Systolic/diastolic BP

Temperature (oral preferred, ear or axillary allowed)

Respiratory rate
Subjects will be sitting for at least 5 minutes prior and during the measurement of BP, PR, and 
respiration rate. On dosing days, vital signs will be measured prior to IMP administration, once 
during the infusion (at the halfway time point), at the end of infusion, 2 hours after end of 
infusion, and 4 hours after end of infusion. At nondosing visits, vital signs need only be taken 
once during the visit.
12.3.4
Body weight and height
The subject’s body weight (without shoes) will be determined at Screening (Visit 1), Visit 9, and 
at the FV (Visit 20). Height will be measured at Screening (Visit 1) only.
12.3.5
Physical examination
Physical examination (full or brief) will be performed at visits as specified in the schedule of 
study assessments (Table 5.1) and findings will be recorded in the eCRF.
Clinically important abnormal changes in subsequent physical examinations will be recorded as 
AEs. Physical examinations must be documented in source documentation.
12.3.5.1
Full physical examination
The following body systems will be examined as a part of the full physical examination:

General appearance

Ear, nose, and throat

Eyes

Hair and skin

Respiratory

Cardiovascular

GI

Musculoskeletal

Hepatic

Neurological (including limb reflexes)

Mental status
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12.3.5.2
Brief physical examination
The following body systems will be examined as a part of the brief physical examination at the
visits outlined in the schedule of assessments (Table 5.1):

General appearance

Ear, nose, and throat

Eyes

Skin

Respiratory

GI

Neurological (focused assessment of sensitivity and power)
12.3.6
Neurological examination
In addition to the Screening and FV, a full neurological examination should be performed for any 
subject who experiences severe headache (see Section 12.1.10). Neurological examination (full 
or brief) will be performed at visits as specified in the schedule of study assessments (Table 5.1) 
and findings will be recorded in the eCRF.
A full neurological 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.
A brief neurological assessment will include a selected assessment of the following: cognition, 
general reflexes, muscle strength, and coordination/cerebellar function.
12.3.7
12-lead ECG
A standard 12-lead ECG will be performed at visits as specified in the schedule of study 
assessments (Table 5.1).
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.
The ECGs will be read by a central reader. The PR, RR, QRS, QT, and corrected QT (QTc) 
intervals and heart rate will be assessed.
For the QTc, the following correction formula will be applied:
Fridericia’s correction: QTc = QT/RR0.33
The investigator may consult with the cardiologist at the central ECG laboratory to confirm the 
presence of a clinically significant ECG abnormality. It remains the responsibility of the 
investigator to decide whether an ECG finding is of clinical significance on the basis of the 
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complete clinical picture and whether this finding influences the subject’s participation in the 
study.
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 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 
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, clinic/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 and /or printouts of eCRFs are not considered 
acceptable source documents.
Source documents are original records in which raw data are first recorded. These may include 
clinic/hospital/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.
The following data will be recorded directly in the eCRF and will not appear in a separate source 
document as defined above.
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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 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.
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. 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.
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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 
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 
trial 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).
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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 SAP.
14.1
Definition of analysis sets
Enrolled Set:
The Enrolled Set (ES) will consist of all subjects who have given informed consent.
Randomized Set:
The Randomized Set (RS) will consist of all subjects randomized into the study at the first 
randomization visit.
Safety Set:
The Safety Set (SS) will consist of all subjects in the RS, who have received at least 1 dose of 
IMP.
Safety variables will be analyzed using the SS.
It is expected that subjects will receive treatment as randomized and hence safety analyses will 
be based on the randomized treatment group. However, if after unblinding it is determined that a 
subject has received the incorrect treatment based on the randomization schedule, then for safety 
analyses the subject will be allocated to the actual treatment they received in the respective 
Dosing Period.
Full Analysis Set:
The Full Analysis Set (FAS) will consist of all subjects in the SS, who have a Baseline and least 
1 post-Baseline QMG measurement during Dosing Period 1 (up to and including Visit 9, ie, 
Day 29).
The FAS is the primary analysis set for efficacy analyses. As for the SS, in the case of 
mistreatment, subjects will be primarily analyzed as treated. However, if applicable, sensitivity 
analysis will also be performed according to the randomized treatment group.
Per-Protocol Set:
The Per-Protocol Set (PPS) is a subset of the FAS, consisting of those subjects who had no 
important protocol deviations affecting the primary efficacy variable, as confirmed during a 
pre-analysis data review meeting conducted prior to study unblinding. Post-Baseline deviations 
will not necessarily lead to total exclusion of a subject from the PPS but may lead to exclusion of 
specific data.
Analysis of the primary efficacy variable will be repeated using the PPS.
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Pharmacokinetic Per-Protocol Set:
The PK-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations affecting the plasma concentration of UCB7665.
Pharmacodynamic Per-Protocol Set:
The PD-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviation affecting the serum concentrations of total IgG or IgG subclasses.
14.2
General statistical considerations
All analyses will be performed using SAS® version 9.3 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.
The Treatment Groups for Dosing Period 1 will be as follows:

Placebo

UCB7665 7mg/kg
For Dosing Period 2 and the Observation Period the following Treatment Groups will be 
considered for analysis:

Placebo - UCB7665 7mg/kg

Placebo - UCB7665 4mg/kg

UCB7665 7mg/kg - UCB7665 7mg/kg

UCB7665 7mg/kg - UCB7665 4mg/kg
These Treatment Groups will be used for all safety and efficacy analyses.
Unless stated otherwise, all statistical tests will be 1-sided and conducted at 0.05 alpha levels
(due to the character of the study, no alpha adjustment for multiplicity will be done). For Dosing 
Period 2, only descriptive analyses will be performed.
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 in Dosing 
Period 1, and measurement-specific Baseline values will be defined in the SAP.
14.3
Planned efficacy analyses
For all efficacy analyses the Treatment Groups used for analysis during Dosing Period 1 and 
during Dosing Period 2/Observation Period will be as defined in Section 14.2. Efficacy 
endpoints will be analyzed using descriptive statistics for data obtained during 
Treatment Period 2 and Observation Period. Further details will be provided in SAP.
14.3.1
Analysis of the primary efficacy variable
The primary efficacy variable is the change from Baseline in QMG score to Visit 9 (Day 29), 
prior to the first infusion of IMP in Dosing Period 2.
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A 1-sided hypothesis test will be performed to test the primary hypothesis of superiority of 
UCB7665 7mg/kg vs placebo at Visit 9. The null hypothesis is that there is no difference in the 
change from Baseline between Treatment Groups. The alternative hypothesis is that the mean 
change from Baseline in QMG score is smaller in the UCB7665 7mg/kg group than the placebo 
group.
The primary analysis of the primary variable will be based on a mixed model repeated measures 
(MMRM) analysis of covariance (ANCOVA) that includes terms for treatment group, week, the 
Baseline QMG score, and the interaction between treatment group and week. The model will 
define patient as a random effect and utilize an unstructured covariance pattern.
Least Squares (LS) Means for changes from Baseline at Visit 9 for each treatment group will be 
presented together with LS mean differences (UCB7665 - 7mg/kg vs placebo) and 1-sided 95% 
confidence interval (CI).
For subjects who prematurely withdraw for any reason before Visit 9 (Day 29), data collected 
during the PEOT Visit will be used to impute QMG scores at the next consecutive visit.
Different sensitivity analyses to evaluate the effect of missing observations on the primary 
analysis findings will be done. The first sensitivity analysis will be performed in the same way as 
the primary analysis for the PPS. A further analysis will utilize the Last Observation Carried 
Forward (LOCF) approach; missing values will be replaced by the last observed post-Baseline 
value of the variable and the analysis will be performed on the resulting dataset.
14.3.2
Other efficacy analyses
The secondary variables and change from Baseline in QMG score, MG-Composite score,
MGADL score, MGII score, muscle weakness severity and fatigability scale score and fatigue 
scale score, at each assessed post-Randomization Visit (during Dosing Period 1 including Visit 
9) will also be analyzed utilizing the MMRM approach similarly to the change from Baseline in 
QMG for the FAS as described in Section 14.3.1.
QMG, MG-Composite, and MGADL responder rates at each assessed post-Randomization Visit 
(during Dosing Period 1) will be compared between the 2 Treatment Groups utilizing Fisher’s 
exact test.
The percentage of subjects with each MGFA classification at each scheduled assessment during 
Treatment and Observation Periods will be calculated.
Psychometric analyses of the newly developed measures MG muscle weakness severity and 
fatigability and fatigue scales will be performed blinded from treatment arms. The association 
between PROs and clinical variables will also be explored, as well as the association between the 
various PROs. A psychometric analysis of the MG muscle weakness severity and fatigability 
scale and fatigue scale using Rasch analysis will be performed, but reported separately from the 
CSR.
Changes in MCD of the IPI, and normal fiber pairs in jitter (SFEMG) will be summarized using 
descriptive statistics, by treatment group and time point, including changes from Baseline. A 
reduction in MCD of ≥9µs in jitter (SFEMG) studies will also be summarized using descriptive 
statistics, by treatment group and time point, including changes from Baseline.
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14.4
Planned other and exploratory analyses
14.4.1
Safety analyses
For all safety analyses the Treatment Groups used for analysis during Dosing Period 1 and 
during Dosing Period 2/Observation Period will be as defined in Section 14.2 and as described in 
the SAP.
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 Medical Dictionary for Regulatory 
Activities, 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 IMP, 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.
Adverse events will be assigned to a Dosing Period based on the start date of the event relative to 
the first dose of IMP received in the respective period.
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.
Exploratory safety biomarkers will be summarized by treatment group and visit using descriptive 
statistics.
Normal vs 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 pulse rate, 
systolic/diastolic BP, temperature, and respiratory rate). Measured values and changes from 
Baseline will be summarized by treatment group.
Physical and neurological examination findings and the results of any pregnancy testing will be 
presented in listings only.
14.4.2
Pharmacokinetic analysis
The PK variable is the plasma concentration of UCB7665. Pharmacokinetic parameters such as 
Cmax and area under the curve will not be derived (eg, by non-compartmental analysis) due to the 
limited sampling performed at each visit.
Individual concentrations of UCB7665 will be listed and summarized at each scheduled time
point. Descriptive statistics of concentrations will be calculated only if at least two thirds of the 
individual data points are quantifiable (≥lower limit of quantification [LLOQ]). Summaries will 
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include 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 LLOQ will be reported with a clear sign indicating that they were below the 
LLOQ. Individual concentrations of UCB7665 will also be displayed graphically.
14.4.3
Pharmacodynamic analysis
For all PD variables, descriptive statistics for the change from Baseline, and percentage change 
from Baseline will be tabulated by treatment group and time point.
The PD variables will include MG-specific autoantibodies
, serum total 
IgG, and IgG subclasses. In addition, for serum total IgG, the minimum value and maximum 
decrease from Baseline (including percentage decrease) will be evaluated and summarized.
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.
14.4.4
Immunological variables
All immunological variables including concentrations of Igs (IgA, IgE, and IgM), serum 
complement levels (C3 and C4) and plasma complement levels (C3a and C5a), and serum BAFF
will be listed and summarized, using descriptive statistics, by Treatment Group and visit 
including changes from Baseline. Concentrations of cytokines will be listed and summarized if 
there are sufficient data. Figures of mean values and changes from Baseline of immunological 
variables may be presented, and will be described in the SAP.
The 
 status (negative or confirmed positive) and either changes in relative mass units from 
Baseline for all scheduled assessments or titres for those confirmed positive will be listed and 
summarized by treatment group.
The 
 antibodies will be listed and summarized by 
treatment group.
14.4.5
Subject exit interview
The anonymous audio-recordings will be analyzed by a third party and reported outside 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 
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.
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14.7
Planned interim analysis and data monitoring
At least three interim analyses will be performed. The first interim analysis for futility will be 
performed once approximately 20 subjects have attended Visit 9, the first visit of the second 
Dosing Period (ie, Day 29). Futility of UCB7665 will be assessed based on QMG score,
MG-Composite score, and MGADL data. In case of futility, the study will be stopped or 
amended. The decision rules for futility will be described in the DMC charter. The second
interim analysis will be conducted after approximately 20 subjects (receiving 6 sc infusions) 
have had Visit 16 (Day 57). Based on this unblinded analysis the safety of UCB7665 will be 
assessed by the DMC. The safety variables to be used and the potential outcomes of the analysis
will be specified in the DMC charter. During this review recruitment will not be stopped. The 
third interim analysis will be performed once all subjects have attended Visit 9 (Day 29), the first 
visit of the second Dosing Period (ie, Day 29). This interim analysis will provide the results for 
the primary variable ‘change from Baseline to Visit 9 (Day 29) in the QMG score’, and 
secondary variables ‘change from Baseline to Visit 9 (Day 29) in MG-Composite score’ and
‘change from Baseline to Visit 9 (Day 29) in the MGADL score’. For the third interim analysis 
the DMC will not be utilized.
The analyses will be described in a separate Interim SAP. The first interim analysis will utilize 
all efficacy data (as specified in the DMC charter), which will be available at the time the 20th
subject attended Visit 9. The second interim analysis will utilize all safety data (as specified in 
the DMC charter), which will be available at the time the 20th subject attended Visit 16. For all 
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.
If needed, subsequent DMC meetings will take place. The timing of further interim analyses and 
reviews of data by DMC will be decided by the DMC. Ad hoc DMC meetings can be held for 
reasons determined appropriate by the sponsor.
The deliberations and decisions of the DMC will be formally minuted/documented.
A detailed description of the DMC composition, processes, and responsibilities will be provided 
in a separate DMC charter.
14.8
Determination of sample size
The primary efficacy endpoint of this study is change in QMG score from Baseline to Visit 9
(Day 29).
The sample size calculation use a 1-sided 
 significance level, an estimate (based on a 
 CI) 
of the SD for change in QMG of 
 and an anticipated treatment effect of 
 (Zinman et al, 
2007).
Assuming a treatment difference of 
 points in the mean change from Baseline in QMG at 
Visit 9 between the placebo and UCB7665 treatment arm with SD equal to 
 a sample size of 
 subjects (
 for each treatment group) provides >90% power to detect a treatment difference.
Further it will be assumed that approximately 
 of the randomized subjects cannot be utilized 
for the FAS and, hence 
 subjects will be randomized.
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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 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.
All studies conducted at centers in the USA must include the use of a Health Insurance 
Portability and Accountability Act Authorization 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 
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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), 
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 clinic/hospital
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study).
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.
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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.
Barnett C, Katzberg H, Nabavi M, Bril V. The quantitative myasthenia gravis score: comparison 
with clinical, electrophysiological, and laboratory markers. J Clin Neuromuscul Dis. 
2012;13(4):201-5.
Barnett C, Bril V, Kapral M, Kulkarni A, Davis AM. A conceptual framework for evaluating 
impairments in myasthenia gravis. PLos One. 2014;9(5).
Barnett C, Bril V, Kapral M, Kulkarni A, Davis AM Development and validation of the 
Myasthenia Gravis Impairment Index. Neurology. 2016; 87(9): 879–886.Barth D, Nabari MN, 
Ng E, Nwe P, Bril V; Comparison of IVIg and PLEX in patients with myasthenia gravis. 
Neurology. 2011;76(23):2017-23.
Benatar M, Sanders DB, Burns TM, Cutter GR, Guptill JT, Baggi F,; Task Force on MG Study 
Design of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of 
America. Recommendations for myasthenia gravis clinical trials. Muscle Nerve. 2012 
Jun;45(6):909-17. doi: 10.1002/mus.23330. PubMed PMID: 22581550.
Burns TM, Conaway M, Sanders DB; MG Composite and MG-QOL15 Study Group. The MG 
Composite: A valid and reliable outcome measure for myasthenia gravis. Neurology. 2010 May 
4;74(18):1434-40. 
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002.
Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic 
strategies.Lancet Neurol. 2015;14(10):1023-36.
Howard JF Jr, Barohn RJ, Cutter GR, Freimer M, Juel VC, Mozaffar T, Mellion ML, Benatar 
MG, Farrugia ME, Wang JJ, Malhotra SS, Kissel JT; MG Study Group. A randomized, 
double-blind, placebo-controlled phase II study of eculizumab in patients with refractory 
generalized myasthenia gravis. Muscle Nerve. 2013 Jul;48(1):76-84. doi: 10.1002/mus.23839. 
Epub 2013 Apr 30. PubMed PMID: 23512355.
Johnsen J, Pathogenesis in immune thrombocytopenia: new insights. American Society of 
Hematology, Hematology 2012:306-312.
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. 
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Muppidi S. The myasthenia gravis-specific activities of daily living profile. Ann N Y Acad Sci, 
2012. 1274: p. 114-9 
Muppidi S, Wolfe GI, Conaway M, Burns TM; MG COMPOSITE AND MG-QOL15 STUDY 
GROUP. MG-ADL: still a relevant outcome measure. Muscle Nerve. 2011 Nov;44(5):727-31.
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.
Sanders, Single fiber EMG. In: Encyclopedia of the Neurological Sciences (Second Edition):
Elsevier; 2014: 169–172.
Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis 
activities of daily living profile. Neurology. 1999 Apr 22;52(7):1487-9. 
World Health Organization. Guidelines for treatment of tuberculosis (Fourth edition). Geneva: 
World Health Organization; 2010.
Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a randomized 
controlled trial. Neurology. 2007 Mar 13;68(11):837-41.
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18.2
MG-Composite score
Figure 18.2: MG-Composite score
(Burns, 2010)
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18.9
Diagnosis of anaphylactic reactions
Anaphylaxis is highly likely when any of the following 3 criteria is fulfilled (Sampson et al, 
2006):
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal 
tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a.
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow [PEF], hypoxemia)
b. Reduced blood pressure [BP] or associated symptoms of end-organ dysfunction (eg, 
hypotonia [collapse], syncope, incontinence)
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient (minutes to several hours):
a.
Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips 
tongue-uvula)
b.
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)
c.
Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)
d.
Persistent GI symptoms (eg, crampy abdominal pain, vomiting)
3. Reduced blood pressure after exposure to known allergen for that subject (minutes to several 
hours): Systolic BP of less than 90mmHg or greater than 30% decrease from the subject’s 
Baseline systolic BP value.
18.10
Headache Questionnaire
Table 18.2:
Headache Questionnaire
Symptoms & Frequency of Severe Headaches 
1. Date of collection: 
Time of collection: 
DD 
MMM 
YY 
HH 
MM 
2. Is the subject suffering from a severe headache? 
Yes 
No 
a. Which of the following best describes how the subject is affected? 
Able to function normally 
Activity impaired to some degree 
Activity severely impaired 
Bed rest required 
b. Rate your pain on a scale of 0 - 10: 
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Table 18.2:
Headache Questionnaire
Symptoms & Frequency of Severe Headaches 
3. During the course of this headache, has the subject experienced any of the following? 
a. Nausea: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
b. Vomiting: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
c. Dizziness: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
i. Vertigo: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
ii. Nonvertigo: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
d. Increased neck pain or stiffness: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
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Table 18.2:
Headache Questionnaire
Symptoms & Frequency of Severe Headaches 
e. Increased sensitivity to light: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
f. Increased sensitivity to noise: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
g. Increased sensitivity to smell: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
h. Pain made worse by routine physical activity: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
i. Pain on one side of head only: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
j. Pulsating/throbbing headaches: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
k. Weakness on one side: 
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Table 18.2:
Headache Questionnaire
Symptoms & Frequency of Severe Headaches 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
l. Seeing shimmering lights, lines, dark spots, other shapes or colors before the eyes, before or during the 
headache and lasts more than a few minutes but less than an hour: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
m. One-sided numbness of lips, tongue, fingers, or legs that migrates or moves and starts before the 
headache becomes severe and lasts less than an hour: 
0 = Never 
1 = Rarely 
2 = Less than half the time 
3 = Half the time or more 
General 
 The questionnaire should be administered via an interview with
the subject.
 The recall period for the first time the questionnaire is
administered is since the severe headache began.
 The recall period for subsequent questionnaires should be since 
the prior administration of the questionnaire, not since the start of 
the severe headache.
 Mark an X in only 1 box for each question. Do not write in any
other choices.
 Transcribe the subject’s responses to the eCRF screen.
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DD MMM YYYY
(v.2009-09-09)
18.12
Protocol Amendment 1
Rationale for the amendment
The protocol has been amended to incorporate the feedback from the U.S. Food and Drug 
administration (FDA) received on 09 December 2016 and the new company standard in TB 
management.
In addition, minor administrative changes have been made.
The following shows the changes made in Amendment 1 compared to the original protocol, 
dated 21 Oct 2016.
Modifications and changes
Global changes
The following changes were made throughout the protocol:

Secondary efficacy variables and other efficacy variables were updated. Statistical analyses 
sections were updated accordingly.

Sections covering collection of exploratory biomarker samples and exploratory safety 
biomarker sample were simplified.

Exploratory biomarker sampling was separated from exploratory safety biomarker sampling.

Timing of the IRT to be called was updated (at Screening and on dosing visits only, not every 
single visit).

Wording for home visit at Visit 20 to be conducted at home was revised throughout the 
protocol. Now the home visits are allowed at Visits 17 and 19.

The C-SSRS was added to address the request of the FDA that prospective assessments for 
suicidality should be included in clinical trials involving all drugs for neurological 
indications.

The detailed tuberculosis assessment was added to ensure the subject safety.

The term on-demand treatment was revised into chronic-intermittent treatment.

Editorials and revisions on abbreviations were implemented.
Specific changes
Change #1
1
SUMMARY, 3rd paragraph
The study will consist of 3 Periods: Screening, Treatment, and Observation. After Screening, 
subjects will enter the Treatment Period, which will consist of 2 successive Dosing Periods. 
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Subjects will receive 3 doses of investigational medicinal product (IMP) at weekly intervals 
during both Dosing Period 1 and Dosing Period 2. Dosing Period 1 will be 4 weeks, with 2 
parallel arms (UCB7665 7mg/kg or placebo). Dosing Period 2 will be 2 weeks, with 2 parallel 
treatment arms (UCB7665 7mg/kg or UCB7665 4mg/kg).
Has been changed to:
The study will consist of 3 Periods: Screening, Treatment, and Observation. After Screening, 
subjects will enter the Treatment Period, which will consist of Dosing Period 1 followed by 
Dosing Period 2. Subjects will receive 3 doses of investigational medicinal product (IMP) at 
weekly intervals during each dosing period as follows:

Dosing Period 1 will be 4 weeks, with 2 parallel arms (UCB7665 7mg/kg or placebo).

Dosing Period 2 will be 2 weeks, with 2 parallel treatment arms (UCB7665 7mg/kg or 
UCB7665 4mg/kg).
Change #2
1
SUMMARY, 4rd and 5th paragraph
A Data Monitoring Committee (DMC) will oversee at least 1 interim analysis for safety and for 
futility during the course of the study (see Section 14.7). Details of the interim analysis will be 
provided in the DMC charter and interim Statistical Analysis Plan (SAP).
The primary efficacy variable will be the change from Baseline in Quantitative MG (QMG) 
score to Visit 9 (Day 29). Other efficacy variables will be the following: change from Baseline in 
MG-Composite score to Visit 9 (Day 29); value and change from Baseline in QMG at each 
scheduled assessment during Treatment and Observation Periods; proportion of QMG responder 
(≥3.0 point improvement from Baseline) at each scheduled assessment during Treatment and 
Observation Periods; value and change from Baseline in MG-Composite score at each scheduled 
assessment during Treatment and Observation Periods; proportion of MG-Composite responder 
(≥3.0 point improvement from Baseline) at each scheduled assessment during Treatment and 
Observation Periods; value and change from Baseline in MG muscle weakness severity and 
fatigue scales at each scheduled assessment during Treatment and Observation Periods; value 
and change from Baseline in MG-Activities of Daily Living (MGADL) at each scheduled 
assessment during Treatment and Observation Periods; and change in mean jitter in single fiber 
electromyography (SFEMG) from Baseline to Visit 9 for the subjects consenting to this 
measurement at participating sites.
Has been changed to:
1
SUMMARY, 5th and 6th paragraph
A Data Monitoring Committee (DMC) will be implemented as described in Section 14.7.
The primary efficacy variable will be the change from Baseline in Quantitative MG (QMG) 
score to Visit 9 (Day 29). The secondary efficacy variables will be the change from Baseline in
MG-Composite score to Visit 9 (Day 29) and the change from Baseline in MG-Activities of 
Daily Living (MGADL) score to Visit 9 (Day 29). Other efficacy variables will be the following:
value and change from Baseline in QMG at each scheduled assessment during Treatment and 
Observation Periods; QMG responder (≥3.0 point improvement from Baseline) at each scheduled 
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Has been changed to:
4.1.3
Other efficacy variables

QMG responder (≥3.0 point improvement from Baseline) at each scheduled assessment 
during Treatment and Observation Periods

MG-Composite responder (≥3.0 point improvement from Baseline) at each scheduled 
assessment during Treatment and Observation Periods
In addition, the following was added:

MGADL responder (≥3.0 point improvement from Baseline) at each scheduled assessment 
during Treatment and Observation Periods
Change #9
Sections 4.2 to 4.4 have been restructured:
4.2 Pharmacokinetic and pharmacodynamic variables
4.2.1
Pharmacokinetic variable
4.2.2
Pharmacodynamic variables
4.3 Immunological variables
4.4 Safety variables
Has been changed to:
4.2 Other and exploratory variables
4.2.1
Safety variables
4.2.2
Pharmacokinetic variable
4.2.3
Pharmacodynamic variables
4.2.4
Immunological variables
Change #10
4.2 Pharmacodynamic variables (previous heading number)
The heading number was changed to the below:
4.2.3
Pharmacodynamic variables
The below was deleted:

Change from Baseline total IgG concentration pre- and post-ADA depletion at each 
scheduled assessment during Treatment and Observation Periods
Change #11
4.3 Immunological variables (previous heading number)
Additional exploratory biomarkers may be investigated if needed using the samples already 
available.
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by certified healthcare professionals, for Visits 17, 19, and 20. The Observation Period begins 
the day after the final dose of IMP (ie, Visit 13, Day 43); Visit 15 (Day 50) is the first visit in the 
Observation Period.
A DMC will be established to monitor mainly safety data during the study. In addition efficacy 
data will be assessed once during the study for futility. The DMC will be unblinded and details 
of the DMC composition, processes, and responsibilities will be documented in the DMC 
charter.
Has been changed to:
5.1 Study description
Observation Period: All subjects must be followed for 8 weeks after the final dose of IMP is 
administered. Subjects will return to the clinic for Visits 15, 16, 18, and 20 for efficacy and for 
safety assessments (see Section 5.2, Schedule of Assessments). Subjects will either return to the 
clinic/hospital, or, if possible and agreed by investigator and subject, have home visits conducted 
by certified healthcare professionals, for Visits 17 and 19. The Observation Period begins the day 
after the final dose of IMP (ie, Visit 13, Day 43); Visit 15 (Day 50) is the first visit in the 
Observation Period.
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Change #15
Changes on the tables and footnotes
Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 FV/PEOT
c
Day
-28 to 
-1
1
2
8
(± 2 
days)
9
15
(± 2 
days)
16
22
(± 2 
days)
29
(± 2 
days)
30
36
(± 2 
days)
37
43
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Written informed consentd
X
Written informed consent for 
genomic substudy
X
Demographic data
X
Verification of inclusion 
/exclusion criteria
X
X
Call or enter IRT to register 
the visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Call to IRT / Randomization
X
X
Withdrawal criteria
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
General medical/procedures 
history
X
Prior and concomitant 
medication
X
X
X
X
X
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
Vital signse
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 FV/PEOT
c
Day
-28 to 
-1
1
2
8
(± 2 
days)
9
15
(± 2 
days)
16
22
(± 2 
days)
29
(± 2 
days)
30
36
(± 2 
days)
37
43
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Body weight, heightf
X
X
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Full physical examination
X
X
Brief physical examination
X
X
Full neurological examination
g
X
X
Brief neurological 
examination
X
X
12-lead ECGh
X
X
X
X
X
X
X
X
X
X
X
Laboratory tests (hematology, 
chemistry, urinalysis)
X
X
X
X
X
X
X
X
X
X
X
X
Serology testing for HIV, 
Hepatitis B, Hepatitis C, and 
active or latent TB
X
Blood sampling for PK of 
UCB7665i
X
X
X
X
X
X
X
X
Blood sampling for DNA 
analysis (optional)
Xj
Xj
Xj
Blood sampling for RNA 
analysis (optional)
Xj
Xj
Xj
Xj
Xj
Serum pregnancy test
X
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 FV/PEOT
c
Day
-28 to 
-1
1
2
8
(± 2 
days)
9
15
(± 2 
days)
16
22
(± 2 
days)
29
(± 2 
days)
30
36
(± 2 
days)
37
43
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
QMG scalen
X
X
X
X
X
X
X
X
X
X
X
X
Muscle weakness severity and 
fatigability scale
X
X
X
X
X
X
X
X
X
X
X
X
X
Fatigue scale
X
X
X
X
X
X
X
X
X
X
X
X
X
MGADL scale
X
X
X
X
X
MGFA classification 
X
X
X
X
SFEMG measuremento
X
X
Headache questionnairep
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Stool sample assessmentq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interview
X
AE=adverse event; BAFF=B-cell activating factor; BL=Baseline; BP=blood pressure; CSF=cerebrospinal fluid; CT=computed tomography; DNA=deoxyribonucleic acid; 
ECG=electrocardiogram; FV=Final Visit; GI=gastrointestinal; HIV=human immunodeficiency virus; IgA=immunoglobulin A; IgE=immunoglobulin E; IgG=immunoglobulin G; 
IgM=immunoglobulin M; IMP=investigational medicinal product; IRT=interactive response technology; LP=lumbar puncture; MG=myasthenia gravis; MGADL=myasthenia 
gravis-Activities of Daily Living; MGFA=Myasthenia Gravis Foundation of America; MRI=magnetic resonance imaging; PEOT=premature end of treatment; 
 PK=pharmacokinetics; PR=pulse rate; RNA=ribonucleic acid; QMG=Quantitative Myasthenia Gravis; 
 
 SFEMG=single fiber electromyogram; TB=tuberculosis; UV=Unscheduled Visit
a Subjects will return to the clinic for Visits 15, 16, and 18; for Visits 17, 19, and 20, subjects with either return to the clinic/hospital, or, if possible and agreed 
by the investigator and subject, have home visits conducted by certified healthcare professionals.
bThis visit is a telephone contact 24 hours post-IMP dose start.
c Subjects who withdraw early will be encouraged to complete the PEOT Visit plus the FV (approximately 8 weeks after the final study drug administration).
e Includes consent for SFEMG for the subjects consenting to this measurement at the participating sites. Additional informed consent is needed for participation 
in the exploratory genomic substudy.
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f Systolic and diastolic BP, pulse rate, temperature, and respiratory rate. On dosing days, vital signs will be measured prior to IMP administration, 15 minutes 
after the start of the infusion, at the end of the infusion, 2 hours after the end of infusion and 4 hours after the end of the infusion. At nondosing visits, vital 
signs need only be taken once during the visit.
gBody weight at Screening will be used for calculation of dose; height will be assessed only at Screening.
hIn addition to Screening and the FV, a full neurological examination should be performed for any subject who experiences severe headache.
j ECGs will be read by a central reader.
Pre- and postdose at Visits 2, 4, 6, 9, 11, and 13; postdose samples are to be taken 4 hours after the infusion has ended.
j Blood sample to be taken prior to dosing of IMP.
nUrine pregnancy test will be performed using a dipstick test; a positive urine pregnancy test must be confirmed using a serum pregnancy test.
l Serum safety biomarkers levels measured at Baseline for all subjects and during follow up only in subjects with severe headache or moderate to severe GI
disturbances.
qAt Baseline and subsequently only in subjects with infusion reaction.
n Subjects must be off pyridostigmine (or any 
 inhibitor medication) from midnight before testing when medically safe to do so to 
standardize testing, but if not medically appropriate, then the treatment can be continued but the testing should be performed as best as possible at the same 
timeframe post last 
 inhibitor dosing for each evaluation during the study.
t For subjects consenting to this measurement at the participating sites; subjects should not take pyridostigmine from midnight before testing when medically 
safe to do so to standardize testing, but if not medically appropriate, then the treatment can be continued but the testing should be performed as best as possible 
at the same timeframe post last 
 inhibitor dosing for each evaluation during the study.
uThis 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.
vStool 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.
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Has been changed to:
Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Written informed consent
e
X
Written informed consent 
for genomic substudy
X
Demographic data
X
Verification of inclusion 
/exclusion criteria
X
X
Call or enter IRT to 
register the visit
X
X
X
X
X
X
Call or enter IRT/ 
Randomization
X
X
Withdrawal criteria
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
General medical/
procedures history
X
Prior and concomitant 
medication
X
X
X
X
X
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
Vital signsf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight, heightg
X
X
X
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Full physical 
examination
X
X
Brief physical 
examination
X
X
Full neurological 
examinationh
X
X
Brief neurological 
examination
X
X
Query for suicidalityi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECGj
X
X
X
X
X
X
X
X
X
X
X
Laboratory tests 
(hematology, chemistry, 
urinalysis)
X
X
X
X
X
X
X
X
X
X
X
X
Serology testing for HIV, 
Hepatitis B, and Hepatitis 
C
X
IGRA tuberculosis testk
X
Tuberculosis Signs and 
Symptoms questionnaire
X
X
Blood sampling for PK 
of UCB7665l
X
X
X
X
X
X
X
X
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
MGFA classification 
X
X
X
X
SFEMG measurementr
X
X
Headache questionnaires
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Stool sample assessmentt
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interview
X
AE=adverse event; BAFF=B-cell activating factor; BL=Baseline; BP=blood pressure; CSF=cerebrospinal fluid; CT=computed tomography; DNA=deoxyribonucleic acid; 
ECG=electrocardiogram; FV=Final Visit; GI=gastrointestinal; HIV=human immunodeficiency virus; IgA=immunoglobulin A; IgE=immunoglobulin E; IgG=immunoglobulin G; 
IGRA= interferon-gamma release assay; IgM=immunoglobulin M; IMP=investigational medicinal product; IRT=interactive response technology; LP=lumbar puncture; 
MG=myasthenia gravis; MGADL=myasthenia gravis-Activities of Daily Living; MGFA=Myasthenia Gravis Foundation of America; MRI=magnetic resonance imaging; 
PEOT=premature end of treatment; PK=pharmacokinetics; PR=pulse rate; RNA=ribonucleic acid; QMG=Quantitative Myasthenia Gravis; 
 
 SFEMG=single fiber electromyogram; TB=tuberculosis; UV=Unscheduled Visit
a Subjects will return to the clinic/hospital for Visits 15, 16, 18, and 20; for Visits 17 and 19 subjects will either return to the clinic/hospital, or, if possible and 
agreed by both the investigator and subject, have home visits conducted by certified healthcare professionals.
b This visit is a telephone contact 24 hours post-IMP dose start.
c Subjects who withdraw early will be encouraged to complete the PEOT Visit plus the FV (approximately 8 weeks after the final study drug administration).
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 Includes consent for SFEMG for the subjects consenting to this measurement at the participating sites. Additional informed consent is needed for participation 
in the exploratory genomic substudy.
f Systolic and diastolic BP, pulse rate, temperature, and respiratory rate. On dosing days, vital signs will be measured prior to IMP administration, 15 minutes 
after the start of the infusion, at the end of the infusion, 2 hours after the end of infusion and 4 hours after the end of the infusion. At nondosing visits, vital 
signs need only be taken once during the visit.
g Body weight at Screening and at Visit 9 will be used for calculation of dose; height will be assessed only at Screening.
h In addition to Screening and the FV, a full neurological examination should be performed for any subject who experiences severe headache.
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i A query for suicidal ideation will be asked by Investigator at each clinical visit (including Visit 17 or Visit 19 when it is conducted at the clinic). A full C-SSRS 
assessment will be performed only when subject has a positive response to the suicidal ideation query. If a subject has active suicidal ideation as confirmed by 
the answer ‘Yes’ to Question 4 or Question 5 of the C-SSRS assessments, the subject will be excluded or withdrawn from the study and immediately referred to 
a Mental Healthcare Professional
j ECGs will be read by a central reader. 
k The IGRA test will be performed in a central laboratory. Subject should not be dosed until IGRA result is available and negative.
l Pre- and postdose at Visits 2, 4, 6, 9, 11, and 13; postdose samples are to be taken 4 hours after the infusion has ended.
m Blood sample to be taken prior to dosing of IMP.
n Urine pregnancy test will be performed using a dipstick test; a positive urine pregnancy test must be confirmed using a serum pregnancy test.
p Sampling for exploratory safety biomarkers at Baseline (Visit 2) and 4 hours post dosing (Visit 2) for all subjects. During follow up only in subjects with severe 
headache and/or moderate to severe GI disturbances.
q Sampling at Baseline for all subjects and subsequently only in subjects with infusion reaction.
s Subjects must be off pyridostigmine (or any 
 inhibitor medication) from midnight before testing when medically safe to do so to
standardize testing, but if not medically appropriate, then the treatment can be continued but the testing should be performed as best as possible at the same 
timeframe post last any 
 inhibitor dosing for each evaluation during the study.
t For subjects consenting to this measurement at the participating sites; subjects should not take pyridostigmine from midnight before testing when medically 
safe to do so to standardize testing, but if not medically appropriate, then the treatment can be continued but the testing should be performed as best as possible 
at the same timeframe post last 
 inhibitor dosing for each evaluation during the study. If pyridostigmine is taken, the time must be documented.
u 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.
v 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.
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Change #16
5.4.1
Choice of study design and endpoints
The primary objective of the study is to evaluate the clinical efficacy of UCB7665 as an on-
demand treatment for subjects with moderate to severe generalized MG.
During the first Treatment Period a 2-arm parallel design study will allow comparison of the 
change from Baseline in QMG score to Visit 9 (Day 29) between IMP and placebo.
The choice of the primary outcome measures and the timing of approximately 4 weeks after the 
first dose of study drug are predicted to be the optimal approach to measure improvements based 
on effect seen in other therapies and recommendations of the Scientific Advisory Board of the 
MGFA (Barth 2013; Benatar 2012; Howard 2013). Then the second Dosing Period with a 
rerandomization allows for additional supportive data to be evaluated as well as minimizes the 
need for prolonged exposure of some subjects to placebo.
Has been changed to:
5.4.1
Choice of study design and endpoints
The primary objective of the study is to evaluate the clinical efficacy of UCB7665 as a chronic-
intermittent treatment for subjects with moderate to severe generalized MG. Additionally, this 
study will provide data for future study planning, whether for chronic-intermittent treatment or a 
longer therapy option by evaluating the general concept that UCB7665 has a clinical effect in 
patients with generalized MG.
During the first Treatment Period, a 2-arm parallel design study will allow comparison of the 
change from Baseline in QMG score to Visit 9 (Day 29) between UCB7665 7mg/kg and placebo.
The choice of the primary efficacy outcome measures and the timing of approximately 4 weeks 
after the first dose of study drug are predicted to be the optimal approach to measure 
improvements based on effect seen in other therapies and recommendations of the Scientific 
Advisory Board of the MGFA (Barth 2013; Benatar 2012; Howard 2013). Then the second 
Dosing Period with a rerandomization allows for additional supportive data to be evaluated as 
well as offering the placebo subjects a chance to receive UCB7665.
Change #17
6.1 Inclusion criteria
The following inclusion criterion was amended.
6. Female subjects of child bearing 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 
study drug 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 2 months after their final dose of study drug.
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:
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Has been changed to:
6.1 Inclusion criteria
6. Female subjects of child bearing 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 
study drug 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 2 months after their final dose of study drug. 
According to the International Council for Harmonisation (ICH) M3 (R2), 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 #18
The following exclusion criteria were amended.
6.2.1
Exclusion criteria related to health status
7. Subject has QMG score of <10.5 at Baseline.
12. Subject has 12-lead ECG with changes considered to be clinically significant upon medical 
review.
15. Subject has >1.5x upper limit of normal (ULN) of any of the following: alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or 
>ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert’s syndrome). If 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 randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin 
but <1.5xULN, 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, 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 (>1.5xULN) may 
be repeated once for confirmation. This includes rescreening.
21. 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 (TB) or who tests positive for HIV, Hepatitis B, or Hepatitis C at the Screening 
Visit.
22. Subject has a family history of primary immunodeficiency.
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Has been changed to:
6.2.1
Exclusion criteria related to health status
7. Subject has QMG score of <11 at Baseline.
12. Subject has 12-lead ECG with changes considered to be clinically significant upon medical 
review. The ECG contains findings that, according to the sponsor, may represent a significant 
abnormality. The clinical significance of the findings needs to be assessed by the investigator 
to determine eligibility as defined by the protocol, and any queries regarding continuation of 
the subject must be addressed with the medical monitor.
15. Subject has >2x upper limit of normal (ULN) of any of the following: alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or 
>ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert’s syndrome). If 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 randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin 
but <1.5xULN, 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, 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 (>2xULN) may 
be repeated once for confirmation. This includes rescreening.
21. Subject has a history of clinically relevant ongoing chronic infections including but not 
limited to human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, or who tests 
positive for HIV, Hepatitis B, or Hepatitis C at the Screening Visit.
22. Subject has a family history (immediate family member) of primary immunodeficiency.
Change #19
The following exclusion criteria were amended. Exclusion criterion #29 was deleted.
6.2.2
Exclusion criteria related to concomitant medications/procedures
27. 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.
28. Subject has not completed the washout period for the immunosuppressants, biologics, and 
other therapies as detailed in Table 6.1.
29. Subjects receiving immunoadsorption treatment.
30. Subject had a thymectomy in the past 6 months, a history of thymoma World Health 
Organization grade B2 or B3, or Masaoka grade III or IV, or thymoma requiring 
chemotherapy and/or radiotherapy.
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Has been changed to:
6.2.2
Exclusion criteria related to concomitant medications/procedures
27. 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 
monitoring has shown they did not return to normal range.
28. Subject has been treated with the immunosuppressants, biologics, and other therapies as 
detailed in the recent timeframe as detailed in Table 6.1 OR has not been on stable dosing 
regimens of the medications as detailed in Table 7.1.
29. Exclusion Criterion 29 was deleted per Protocol Amendment 1.
30. Subject had a thymectomy in the past 6 months, a history of thymoma World Health 
Organization grade B2 or B3, or Masaoka grade III or IV, or history of a thymoma requiring 
chemotherapy and/or radiotherapy.
Change #20
Table 6.1: Washout periods for immunosuppressants, biologics, and other therapies
Generic name (commercial/trade names)
Washout Period relative to Baseline Visit 
(regardless of route)
Others
Intravenous immunoglobulin
Has been changed to:
Table 6.1: No treatment periods for exclusionary immunosuppressants, biologics, and other 
therapies
Generic name (commercial/trade names)
Period relative to Baseline Visit (regardless of 
route)
Others
Intravenous or subcutaneous immunoglobulin
Change #21
The below section was added:
6.2.3
Exclusion criteria related to other risks
31 Subject has a lifetime history of suicide attempt (including an 
 
 or has suicidal ideation in the past 6 months as indicated by a 
positive response (Yes) to either Question 4 or Question 5 of the Columbia Suicide Severity 
Rating Scale (C-SSRS) at Screening.
32 Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or 
latent tuberculosis infection (LTBI), or current/history of nontuberculous mycobacterial 
infection (NTMBI) are excluded.
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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. LTBI (see Section 12.3.1 for further details and instructions).
d. NTMBI is defined as a group of lung infections caused by mycobacteria different from 
mycobacterium tuberculosis infections.
Change #22
6.3 Rescreening and Rechecking
Subjects with isolated results that are outside the specified ranges and that are deemed potentially 
clinically nonsignificant will be allowed to rescreen at the discretion of the investigator, 
following discussion with the sponsor’s medical monitor/study physician, if appropriate.
If a subject has 1 isolated test result outside the specific range which is deemed clinically 
significant, the abnormal value may be rechecked at the discretion of the investigator, following 
discussion with the sponsor’s 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.
Has been changed to:
Subjects with isolated results that are outside the specified ranges and that are deemed potentially 
clinically significant will be allowed to rescreen at the discretion of the investigator, following 
discussion with the sponsor’s medical monitor/study physician, if appropriate. 
If a subject has 1 isolated test result outside the specific range which is deemed clinically 
nonsignificant, the abnormal value may be rechecked at the discretion of the investigator, 
following discussion with the sponsor’s 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.
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Change #23
6.4 Withdrawal criteria
Subjects MUST be withdrawn from IMP if any of the following events occur:
1. Subject develops an illness or has a change in health status that would interfere with his/her 
continued participation, including but not limited to:
The below was added:

Subject has a TB test that is confirmed positive or any further evidence suggestive of 
potential TB infection (eg, exposure) and further examinations result in a diagnosis of 
active TB or LTBI (refer to Section 12.3.1) for further details and instructions.

If an NTMBI is identified during a study, the same withdrawal procedures as those used 
for an active TB infection identified during the study should be followed.
Additionally, the below was added:
8. Subject has active suicidal ideation as indicated by a positive response (Yes) to either 
Question 4 or Question 5 of the “Since Last Visit” version of the C-SSRS. The subject 
should be referred immediately to a Mental Healthcare Professional.
Change #24
7.8.1
Permitted concomitant medication
The following was added:
Subjects should not take pyridostigmine (or any 
 inhibitor medication) from 
midnight before testing when medically safe to do so to standardize testing, but if not medically 
appropriate, then the treatment can be continued but the testing should be performed as best as 
possible at the same timeframe post last or any 
 inhibitor medication 
inhibitor dosing for each evaluation during the study.
Change #25
7.8.2
Prohibited concomitant treatments (medications and therapies)

Dexamethasone
3rd paragraph:
If a subject needs or takes any prohibited medication or therapy (except IVIg, PLEX, 
dexamethasone, or rituximab), the investigator will (where possible) discuss with the sponsor 
study physician and a decision will be made whether the subject can continue in the study or 
must be withdrawn. If the subject is treated with IVIg, rituximab, or PLEX, the subject must be 
withdrawn from the IMP, but should be encouraged to continue with Observation Period Visits.
Has been changed to:
7.8.2
Prohibited concomitant treatments (medications and therapies)
Dexamethasone was removed from the bullet list and the following text.
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Change #33
8.6 Unscheduled Visit
The following was added:

Query for suicidality (since last visit):
If positive response (Yes), a full C-SSRS will be performed.
Change #34
9.5 Single Fiber EMG, 1st paragraph: 
At participating sites, subjects consenting to SFEMG measurement should not take 
pyridostigmine from midnight before testing when medically safe to do so to standardize testing, 
but if not medically appropriate, then the treatment can be continued but the testing should be 
performed as best as possible at the same timeframe post last 
 inhibitor dosing for each 
evaluation during the study. […]
Has been changed to:
9.5 Single Fiber EMG, 1st paragraph:
At participating sites, subjects consenting to SFEMG measurement should not take 
pyridostigmine from midnight before testing when medically safe to do so to standardize testing, 
but if not medically appropriate, then the treatment can be continued but the testing should be 
performed as best as possible at the same timeframe post last 
 inhibitor dosing for each 
evaluation during the study. If pyridostigmine is taken, the time must be documented.
Change #35
10.2
Pharmacodynamic variables
The following was deleted:

IgG concentrations pre- and post-
 depletion
Change #36
12.1.1.5
Immediate reporting of adverse events
The following AEs must be reported immediately using the Serious Adverse Event form: 

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 12.1.1.3)

AE of interest (see Section 12.1.1.4)
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Has been changed to:
12.1.1.5
Immediate reporting of adverse events
The following AEs must be reported immediately using the SAE Report Form according to the 
procedure in Section 12.1.2.3: 

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 12.1.1.3)

AE of interest (see Section 12.1.1.4)

Confirmed LTBI, active TB, and NTMBI (see Section 12.3.1)
Change #37
The following was added to clarify the suicidality assessment:
12.1.6 Suicidality
At screening, the Investigator will query each subject if he/she has a lifetime history of suicide 
attempt (including an 
 or suicidal ideation 
in the past 6 months. A full C-SSRS “Lifetime recent” assessment will be performed only when
the subject has a positive response to this query. This scale will be assessed by trained study 
personnel. When suicide attempt or suicidal ideation is confirmed by a positive response (Yes) to 
either Question 4 or Question 5 of the C-SSRS, the subject must be excluded and immediately 
referred to a Mental Healthcare Professional.
At each clinical visit, the investigator must query the suicidal ideation since the last visit. A full 
C-SSRS “Since last visit” assessment will be performed only when the subject has a positive 
response to this query. When suicide attempt or suicidal ideation is confirmed by a positive 
response (Yes) to either Question 4 or Question 5 of the C-SSRS, the subject must be withdrawn 
and immediately referred to a Mental Healthcare Professional. The details of C-SSRS will be 
provided in the Study Procedures Manual.
Change #38
12.1.7 Safety signal detection, 1st paragraph
An unblinded DMC will oversee at least 1 interim analysis during the course of the study during 
which the safety and futility of UCB7665 will be assessed.
Has been changed to:
12.1.7 Safety signal detection, 1st paragraph
An unblinded DMC will oversee at least 1 interim analysis during the course of the study during 
which the safety of UCB7665 will be assessed.
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Change #39
Assessment of safety biomarkers was clarified.
12.1.10
Management of moderate or severe diarrhea (previous heading number), 
2nd paragraph
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. In addition, assessment of 
safety biomarkers is required for subjects with moderate to severe GI disturbances including 
diarrhea.
Has been changed to:
12.1.11
Management of moderate or severe diarrhea (new heading number), 2nd paragraph
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. In addition, collection of blood 
samples for assessment of exploratory safety biomarkers is required for subjects with moderate 
to severe GI disturbances including diarrhea.
Change #40
12.2
Laboratory measurements, Table 12.2
Duplicate laboratory tests were removed and footnotes are updated.
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Table 12.2:
Safety laboratory measurements
Hematology
Chemistry
Urinalysis
Pregnancy test
Hematocrit
Calcium
Albumin
Urine HCG
Hemoglobin
Chloride
Protein
Serum HCG
a
Platelet count
Magnesium
Nitrite
RBC count
Electrolytes (calcium, 
phosphate, sodium, 
potassium, chloride, and 
magnesium)
Glucose
WBC count 
(including 
differential)
pH
Phosphate
Protein
ALP
Leukocytes
HbA1c
b
AST
Blood
Hemoglobin (RBC 
and platelet count)
ALT
Bilirubin
Hematocrit
GGT
Urobilinogen
Serology
c
Total and direct  
bilirubin
Ketone
HBsAg
LDH
Creatinine
HCV Ab
Total cholesterol
Glucose
HIV (anti-HIV1 or
anti-HIV2 
antibodies)
LDL - cholesterol
Albumin
Tuberculosis
d
HDL – cholesterol, 
triglycerides
Amylase
Serum biomarkers
e
Creatine kinase
Creatinine
Total protein
Albumin
alpha- and beta–
globulins
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Table 12.2:
Safety laboratory measurements
Hematology
Chemistry
Urinalysis
Pregnancy test
Urea-N
Procalcitonin
hsCRP
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; FSH=follicle 
stimulating hormone; GGT=gamma glutamyltransferase; HbA1c=hemoglobin A1c; HBsAG=hepatitis B surface 
antigen; HCG=human chorionic gonadotropin; HCV Ab=hepatitis C virus antibody; HDL=high density lipoprotein; 
HIV=human immunodeficiency virus; hsCRP=high-sensitivity C-reactive protein; LDH=lactate dehydrogenase; 
LDL=low density lipoprotein; 
; RBC=red blood cell; 
 WBC=white blood cell
Serum pregnancy testing is only performed at Visit 1 and, in the event of a positive pregnancy test, to confirm the 
results of a urine test
HbA1c is performed at Screening only
This serology performed at Screening only
By QuantiFERON-TB Gold® test
Serum biomarkers levels measured at Screening, Baseline, and at each scheduled assessment during Treatment and 
Observation Periods in subjects with severe headache and/or moderate to severe GI disturbance
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Has been changed to:
Hematology
Chemistry
Urinalysis
Pregnancy test
Hematocrit
Electrolytes (calcium, 
phosphate, sodium, 
potassium, chloride, 
and magnesium)
Albumin
Urine HCG
Hemoglobin
Protein
Serum HCG
a
Platelet count
Nitrite
RBC count
ALP
Glucose
WBC count 
(including 
differential)
AST
pH
ALT
Leukocytes
HbA1cb
GGT
Blood
Total and direct 
bilirubin
Bilirubin
Serology
c
Urobilinogen
HBsAg
LDH
Ketone
HCV Ab
Total cholesterol
Creatinine
HIV (anti-HIV1 or
anti-HIV2 antibodies)
LDL - cholesterol
HDL – cholesterol, 
triglycerides
Tuberculosis
d
Amylase
Exploratory Safety 
Biomarkers
e
Creatine kinase
Creatinine
Total protein
Albumin
alpha- and beta–
globulins
Urea-N
Procalcitonin
hsCRP
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma 
glutamyltransferase; HbA1c=hemoglobin A1c; HBsAG=hepatitis B surface antigen; HCG=human chorionic 
gonadotropin; HCV Ab=hepatitis C virus antibody; HDL=high density lipoprotein; HIV=human immunodeficiency 
virus; hsCRP=high-sensitivity C-reactive protein; LDH=lactate dehydrogenase; LDL=low density lipoprotein; 
RBC=red blood cell; 
 WBC=white blood cell
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a Serum pregnancy testing is only performed at Visit 1 and, in the event of a positive pregnancy test, to confirm the 
results of a urine test
b HbA1c is performed at Screening only
c This serology performed at Screening only
d Interferon-gamma release assay by central laboratory.
e May include but not limited to the following biomarkers listed below. Samples collected for exploratory 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 the subject experienced a severe headache and/or moderate to severe GI disturbance.
Change #41
12.2.1.1
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.
Has been changed to:
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 or 
gastroenterologist.
Change #42
The below was added:12.3.1 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 risk of new or activation of 
LTBI, 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 the risk of TB 
infection in this study (see Section 6.3.2 [Exclusion Criterion 32] and Section 6.4 [Withdrawal 
Criteria 1]). Following are the key considerations of these procedures:
TB Tests at Screening 
IGRA and TB questionnaire are required as indicated in Schedule of Assessments (Table 5.1).

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 must
not be randomized to study drug and, if already randomized, must undergo appropriate 
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LTBI, active TB or other NMTBI identified during study 
During the study, subjects who develop evidence of LTBI or active TB or NMTBI must
immediately stop further administration of study drug and will be referred to an appropriate 
medical specialist for further evaluation.
Confirmed LTBI or active TB or NTMBI must be reported to the Sponsor immediately as 
described above.
Change #43
12.3.6 12-lead ECG
The heading numbering was changed as below:
12.3.7 12-lead ECG
In addition, the below was added:
The investigator may consult with the cardiologist at the central ECG laboratory to confirm the 
presence of a clinically significant ECG abnormality. It remains the responsibility of the 
investigator to decide whether an ECG finding is of clinical significance on the basis of the 
complete clinical picture and whether this finding influences the subject’s participation in the 
study.
Change #44
14.2
General statistical considerations, 5th paragraph
Unless stated otherwise, all statistical tests will be 1-sided and conducted at 0.05 alpha levels. 
For Dosing Period 2, only descriptive analyses will be performed.
Has been changed to:
14.2
General statistical considerations, 5th paragraph
Unless stated otherwise, all statistical tests will be 1-sided and conducted at 0.05 alpha levels
(due to the character of the study, no alpha adjustment for multiplicity will be done). For Dosing 
Period 2, only descriptive analyses will be performed.
Change #45
14.3.1 Analysis of the primary efficacy variable, 2nd paragraph to the last paragraph
A 1-sided hypothesis test will be performed to test the primary hypothesis of superiority of 
UCB7665 7mg/kg vs placebo at Visit 9. The null hypothesis is that there is no difference in the 
change from Baseline between Treatment Groups. The alternative hypothesis is that the mean 
change from Baseline in QMG score is greater in the UCB7665 7mg/kg group than the placebo 
group.
The primary efficacy variable will be analyzed for the FAS using an analysis of covariance 
model with treatment as a factor and Baseline QMG as a covariate. Least Squares (LS) Means 
for changes from Baseline at Visit 9 for each treatment group will be presented together with LS 
mean differences (UCB7665 - 7mg/kg vs placebo) and 1-sided 95% confidence interval (CI). 
Last Observation Carried Forward (LOCF) imputation will be utilized to account for missing 
data at Visit 9.
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The analysis of the primary efficacy variable will repeated for the PPS using the same 
methodology as described above.
Has been changed to:
14.3.1 Analysis of the primary efficacy variable, 2nd paragraph to the last paragraph
A 1-sided hypothesis test will be performed to test the primary hypothesis of superiority of 
UCB7665 7mg/kg vs placebo at Visit 9. The null hypothesis is that there is no difference in the 
change from Baseline between Treatment Groups. The alternative hypothesis is that the mean 
change from Baseline in QMG score is smaller in the UCB7665 7mg/kg group than the placebo 
group.
The primary analysis of the primary variable will be based on a mixed model repeated measures 
(MMRM) analysis of covariance (ANCOVA) that includes terms for treatment group, the 
Baseline QMG score, and the interaction between treatment group and week. The model will 
define patient as a random effect and utilize an unstructured covariance pattern.
Least Squares (LS) Means for changes from Baseline at Visit 9 for each treatment group will be 
presented together with LS mean differences (UCB7665 - 7mg/kg vs placebo) and 1-sided 95% 
confidence interval (CI).
For subjects who prematurely withdraw for any reason before Visit 9 (Day 29), data collected 
during the PEOT Visit will be used to impute QMG scores at the next consecutive visit.
Different sensitivity analyses to evaluate the effect of missing observations on the primary 
analysis findings will be done. The first sensitivity analysis will be performed in the same way as 
the primary analysis for the PPS. A further analysis will utilize the Last Observation Carried 
Forward (LOCF) approach; missing values will be replaced by the last observed post-Baseline 
value of the variable and the analysis will be performed on the resulting dataset.
Change #46
14.3.2 Other efficacy analyses, 1st to 4th paragraph
The change from Baseline in QMG score, MG-Composite score, muscle weakness severity and 
fatigability scale score and fatigue scale score, and MGADL score, at each assessed 
post-Randomization Visit (during Dosing Period 1 including Visit 9) will be analyzed similarly 
to the change from Baseline in QMG for the FAS as described in Section 14.3.1. However 
instead of LOCF, observed cases will be utilized. 
QMG and MG-Composite responder rates at each assessed post-Randomization Visit (during 
Dosing Period 1) will be compared between the 2 Treatment Groups utilizing Fisher’s exact test.
The percentage of subjects with each MGFA classification at each scheduled assessment during 
Treatment and Observation Periods will be calculated.
Psychometric analyses of the newly developed measures MG muscle weakness severity and 
fatigability and fatigue scales will be performed blinded from treatment arms. The association 
between PROs and clinical variables will also be explored, as well as the association between the 
various PROs. A psychometric analysis of the MG muscle weakness severity and Fatigue scale 
using Rasch analysis will be performed, but reported separately from the CSR.
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Has been changed to:
14.3.2 Other efficacy analyses, 1st to 4th paragraph
The secondary variables and change from Baseline in QMG score, MG-Composite score, 
MGADL score, muscle weakness severity and fatigability scale score and fatigue scale score, at 
each assessed post-Randomization Visit (during Dosing Period 1 including Visit 9) will also be 
analyzed utilizing the MMRM approach similarly to the change from Baseline in QMG for the 
FAS as described in Section 14.3.1.
QMG, MG-Composite, and MGADL responder rates at each assessed post-Randomization Visit 
(during Dosing Period 1) will be compared between the 2 Treatment Groups utilizing Fisher’s 
exact test.
The percentage of subjects with each MGFA classification at each scheduled assessment during 
Treatment and Observation Periods will be calculated.
Psychometric analyses of the newly developed measures MG muscle weakness severity and 
fatigability and fatigue scales will be performed blinded from treatment arms. The association 
between PROs and clinical variables will also be explored, as well as the association between the 
various PROs. A psychometric analysis of the MG muscle weakness severity and fatigability 
scale and fatigue scale using Rasch analysis will be performed, but reported separately from the 
CSR.
Change #47
14.4
Planned safety and other analyses
14.4.1 Safety analyses, 5th paragraph
Exploratory safety serum biomarkers will be summarized by treatment group and visit using 
descriptive statistics 
 Figures 
of mean values over time and changes from Baseline may be presented.
Has been changed to:
14.4
Planned other and exploratory analyses
14.4.1 Safety analyses, 5th paragraph
Exploratory safety biomarkers will be summarized by treatment group and visit using descriptive 
statistics.
Change #48
14.4.2.2
Pharmacodynamic analysis 2nd paragraph
The following was deleted:
Figures of mean values over time and changes from Baseline will be presented. The IgG 
concentrations pre- and post-
 depletion at each scheduled assessment will be listed and 
summarized by treatment group and visit.
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Change #49
14.7
Planned interim analysis and data monitoring, 1st and 2nd paragraph
Two interim analyses will be performed. The first interim analysis will be conducted after 20 
subjects (receiving 6 sc infusions) have attended the second visit of the observational period (ie, 
the visit 2 weeks after last dosing). Based on this unblinded analysis the safety of UCB7665 will 
be assessed by the DMC. The safety variables to be used and the decision rules to be applied will 
be specified in the DMC charter. The DMC can either recommend to continue the study as 
planned or to stop the study. In addition futility of UCB7665 will be assessed based on QMG 
score and MG-Composite score data. In case of futility, the study will be stopped. The decision 
rules for futility will be described in the DMC charter. During this review recruitment will not be 
stopped. The second interim analysis will be performed once all subjects have attended Visit 9, 
the first visit of the second Dosing Period (ie, Day 29). This interim analysis will provide the 
results for the primary variable ‘change from Baseline to Visit 9 (Day 29) in the QMG score’ and 
secondary variable ‘change from Baseline to Visit 9 (Day 29) in MG-Composite score’. For the 
second interim analysis the DMC will not be utilized.
The analyses will be described in a separate Interim SAP. The first interim analysis will utilize 
all safety and efficacy data (as specified in the DMC charter), which will be available at the time 
the 20th subject attended Visit 16. For both 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.
Has been changed to:
14.7
Planned interim analysis and data monitoring, 1st and 2nd paragraph
At least three interim analyses will be performed. The first interim analysis for futility will be 
performed once approximately 20 subjects have attended Visit 9, the first visit of the second 
Dosing Period (ie, Day 29). Futility of UCB7665 will be assessed based on QMG score, 
MG-Composite score, and MGADL data. In case of futility, the study will be stopped or 
amended. The decision rules for futility will be described in the DMC charter. The second
interim analysis will be conducted after approximately 20 subjects (receiving 6 sc infusions) 
have had Visit 16 (Day 57). Based on this unblinded analysis the safety of UCB7665 will be 
assessed by the DMC. The safety variables to be used and the potential outcomes of the analysis
will be specified in the DMC charter. During this review recruitment will not be stopped. The 
third interim analysis will be performed once all subjects have attended Visit 9 (Day 29), the first 
visit of the second Dosing Period (ie, Day 29). This interim analysis will provide the results for 
the primary variable ‘change from Baseline to Visit 9 (Day 29) in the QMG score’, and 
secondary variables ‘change from Baseline to Visit 9 (Day 29) in MG-Composite score’ and
‘change from Baseline to Visit 9 (Day 29) in the MGADL score’. For the third interim analysis 
the DMC will not be utilized.
The analyses will be described in a separate Interim SAP. The first interim analysis will utilize 
all efficacy data (as specified in the DMC charter), which will be available at the time the 20th
subject attended Visit 9. The second interim analysis will utilize all safety data (as specified in 
the DMC charter), which will be available at the time the 20th subject attended Visit 16. For all 
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.
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Change #50
14.8
Determination of sample size, 3rd paragraph
Assuming a treatment difference of 3.4 points in the mean change from Baseline in QMG at 
Visit 9 between the placebo and UCB7665 treatment arm with SD equal to 3.4, a sample size of 
40 subjects (20 for each treatment group) provides >90% power to detect a treatment difference. 
Approximately 5% of the randomized subjects cannot be utilized for the FAS and, hence 42 
subjects will be randomized.
Has been changed to:
14.8
Determination of sample size, 3rd paragraph
Assuming a treatment difference of 3.4 points in the mean change from Baseline in QMG at 
Visit 9 between the placebo and UCB7665 treatment arm with SD equal to 3.4, a sample size of 
40 subjects (20 for each treatment group) provides >90% power to detect a treatment difference. 
Further it will be assumed that approximately 5% of the randomized subjects cannot be utilized 
for the FAS and, hence 42 subjects will be randomized.
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18.13
Protocol Amendment 2
Rationale for the amendment
The protocol has been amended to include an additional patient-reported outcome assessment, 
intended as a measure of disease severity. This patient-centered index has been developed for an 
outpatient setting and is sensitive to detect clinical change after interventions, and most 
importantly detect patient-meaningful change. Two additional other efficacy variables have been 
added to capture changes for mean consecutive difference and normal fiber pairs in jitter 
(SFEMG) studies to show the clinical trend from pre- to postdose treatment. 
Furthermore, permitted concomitant medications have been revised to include: modified and 
unmodified dose formulations for cyclosporin; and increased dose strength for tacrolimus. With 
no specific dosing for tacrolimus, dosing is variable in patients with MG, but for transplant 
related immunosuppression, higher doses are cited in literature; therefore a slightly higher fixed 
dose has been allowed. 
Administrative and stylistic changes may not be included in the summary of changes since they 
are considered minor.
The following shows the changes made in Amendment 2 compared to Protocol Amendment 1, 
dated 07 Feb 2017.
Modifications and changes
Global changes
The following changes were made throughout the protocol:

Other efficacy and immunological variables were updated. Statistical analyses sections were 
updated accordingly.

Additional term ‘jitter’ for the SFEMG performance for relevant sections. The term has been 
modified to be presented as ‘jitter (SFEMG) measurement’.

Instructions for subjects using pyridostigmine have been reworded to clarify the requisite for 
the QMG assessment. Subjects ‘should not take’ pyridostigmine.

Study assessments and procedures for treatment visits only have been categorized as pre-
during- and postdose throughout Section 8 in line with the Schedule of Study Assessments.
Specific changes
Change #1
Sponsor Study Physician
Name:
Address:
UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
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Phone:
Fax:
-
Has been changed to:
Name:
Address:
UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
Fax:
-
Change #2
List of Abbreviations – additional abbreviations
IPI
interpotential interval
MCD
mean consecutive difference
MGII
Myasthenia Gravis Impairment Index
Change #3
4.1.3 Other efficacy variables 

Change in mean jitter in SFEMG from Baseline to Visit 9 for the subjects consenting to this 
measurement at the participating sites
Has been changed to:

Change in the percentage of normal fiber pairs in jitter (SFEMG) studies from Baseline to 
Visit 9 for the subjects consenting to this measurement at the participating sites

Change in MCD of the interpotential interval (IPI) in jitter (SFEMG) studies from Baseline 
to Visit 9 for the subjects consenting to this measurement at the participating sites

A reduction in MCD of ≥9µs in jitter (SFEMG) studies will define clinical improvement
Change #4
4.2.4 Immunological variables 

Change from Baseline in serum complement levels (C3 and C4) and plasma complement 
levels (C3a and C5a) at each scheduled assessment during Treatment and Observation 
Periods

 status (negative/positive) and change from Baseline in 
relative mass units at each scheduled assessment during Treatment and Observation Periods

Change from Baseline in serum BAFF levels
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
Change from Baseline in cytokines (in subjects experiencing infusion reactions) at 
assessments during Treatment and Observation Periods
Has been changed to:

Change from Baseline in serum complement levels (C3 and C4) and plasma complement 
levels (C3a and C5a) predose at Visit 2 and 4 hours postdose at each scheduled assessment 
during Treatment and Observation Periods

 status (negative or confirmed positive) and either change 
from Baseline in relative mass units at each scheduled assessment during Treatment and 
Observation Periods or titre for those confirmed positive 

Change from Baseline in serum BAFF levels

Change from Baseline in cytokines pre- and postdose (postdose - in subjects experiencing 
infusion reactions) at assessments during Treatment and Observation Periods
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Change #5
5.2 Schedule of study assessments
Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Written informed consent
e
X
Written informed consent 
for genomic substudy
X
Demographic data
X
Verification of inclusion 
/exclusion criteria
X
X
Call or enter IRT to 
register the visit
X
X
X
X
X
X
Call or enter IRT/ 
Randomization
X
X
Withdrawal criteria
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
General medical/
procedures history
X
Prior and concomitant 
medication
X
X
X
X
X
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
Vital signsf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Body weight, heightg
X
X
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Full physical 
examination
X
X
Brief physical 
examination
X
X
Full neurological 
examinationh
X
X
Brief neurological 
examination
X
X
Query for suicidalityi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECGj
X
X
X
X
X
X
X
X
X
X
X
Laboratory tests 
(hematology, chemistry, 
urinalysis)
X
X
X
X
X
X
X
X
X
X
X
X
Serology testing for HIV, 
Hepatitis B, and Hepatitis 
C
X
IGRA tuberculosis testk
X
Tuberculosis Signs and 
Symptoms questionnaire
X
X
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Table 5.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
MGFA classification 
X
X
X
X
SFEMG measurementr
X
X
Headache questionnaires
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Stool sample assessmentt
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interview
X
AE=adverse event; BAFF=B-cell activating factor; BL=Baseline; BP=blood pressure; CSF=cerebrospinal fluid; CT=computed tomography; DNA=deoxyribonucleic acid; 
ECG=electrocardiogram; FV=Final Visit; GI=gastrointestinal; HIV=human immunodeficiency virus; IgA=immunoglobulin A; IgE=immunoglobulin E; IgG=immunoglobulin G; 
IGRA= interferon-gamma release assay; IgM=immunoglobulin M; IMP=investigational medicinal product; IRT=interactive response technology; LP=lumbar puncture; 
MG=myasthenia gravis; MGADL=myasthenia gravis-Activities of Daily Living; MGFA=Myasthenia Gravis Foundation of America; MRI=magnetic resonance imaging; 
PEOT=premature end of treatment; PK=pharmacokinetics; PR=pulse rate; RNA=ribonucleic acid; QMG=Quantitative Myasthenia Gravis; 
 
 SFEMG=single fiber electromyogram; TB=tuberculosis; UV=Unscheduled Visit
a Subjects will return to the clinic/hospital for Visits 15, 16, 18, and 20; for Visits 17 and 19 subjects will either return to the clinic/hospital, or, if possible and 
agreed by both the investigator and subject, have home visits conducted by certified healthcare professionals.
b This visit is a telephone contact 24 hours post-IMP dose start.
c Subjects who withdraw early will be encouraged to complete the PEOT Visit plus the FV (approximately 8 weeks after the final study drug administration).
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 Includes consent for SFEMG for the subjects consenting to this measurement at the participating sites. Additional informed consent is needed for participation 
in the exploratory genomic substudy.
f Systolic and diastolic BP, pulse rate, temperature, and respiratory rate. On dosing days, vital signs will be measured prior to IMP administration, 15 minutes 
after the start of the infusion, at the end of the infusion, 2 hours after the end of infusion and 4 hours after the end of the infusion. At nondosing visits, vital signs 
need only be taken once during the visit.
g Body weight at Screening and at Visit 9 will be used for calculation of dose; height will be assessed only at Screening.
h In addition to Screening and the FV, a full neurological examination should be performed for any subject who experiences severe headache.
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i A query for suicidal ideation will be asked by Investigator at each clinical visit (including Visit 17 or Visit 19 when it is conducted at the clinic). A full C SSRS 
assessment will be performed only when subject has a positive response to the suicidal ideation query. If a subject has active suicidal ideation as confirmed by 
the answer ‘Yes’ to Question 4 or Question 5 of the C SSRS assessments, the subject will be excluded or withdrawn from the study and immediately referred to a 
Mental Healthcare Professional
j ECGs will be read by a central reader. 
k The IGRA test will be performed in a central laboratory. Subject should not be dosed until IGRA result is available and negative. 
l Pre- and postdose at Visits 2, 4, 6, 9, 11, and 13; postdose samples are to be taken 4 hours after the infusion has ended. 
m Blood sample to be taken prior to dosing of IMP.
n Urine pregnancy test will be performed using a dipstick test; a positive urine pregnancy test must be confirmed using a serum pregnancy test.
p Sampling for exploratory safety biomarkers at Baseline (Visit 2) and 4 hours post dosing (Visit 2) for all subjects. During follow up only in subjects with severe 
headache and/or moderate to severe GI disturbances.
q Sampling at Baseline for all subjects and subsequently only in subjects with infusion reaction.
s Subjects must be off pyridostigmine (or any 
 inhibitor medication) from midnight before testing when medically safe to do so to 
standardize testing, but if not medically appropriate, then the treatment can be continued but the testing should be performed as best as possible at the same 
timeframe post last any 
 inhibitor dosing for each evaluation during the study.
t For subjects consenting to this measurement at the participating sites; subjects should not take pyridostigmine from midnight before testing when medically 
safe to do so to standardize testing, but if not medically appropriate, then the treatment can be continued but the testing should be performed as best as possible at 
the same timeframe post last 
 inhibitor dosing for each evaluation during the study. If pyridostigmine is taken, the time must be documented.
u 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.
v 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.
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Has been changed to:
Table 18.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Written informed consent
e
X
Written informed consent 
for genomic substudy
X
Demographic data
X
Verification of inclusion 
/exclusion criteria
X
X
Call or enter IRT to 
register the visit
X
X
X
X
X
X
Call or enter IRT/ 
Randomization
X
X
Withdrawal criteria
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
General medical/
procedures history
X
Prior and concomitant 
medication
X
X
X
X
X
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
Vital signsf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight, heightg
X
X
X
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Table 18.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Full physical 
examination
X
X
Brief physical 
examination
X
X
Full neurological 
examinationh
X
X
Brief neurological 
examination
X
X
Query for suicidalityi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECGj
X
X
X
X
X
X
X
X
X
X
X
Laboratory tests 
(hematology, chemistry, 
urinalysis)
X
X
X
X
X
X
X
X
X
X
X
X
Serology testing for HIV, 
Hepatitis B, and Hepatitis 
C
X
IGRA tuberculosis testk
X
Tuberculosis Signs and 
Symptoms questionnaire
X
X
Blood sampling for PK 
of UCB7665l
X
X
X
X
X
X
X
X
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Table 18.1:
Schedule of assessments 
Assessments
Screening
Treatment Period
Observation Perioda
UV
Dosing Period 1
Dosing Period 2
Visit
1
2
BL
3b
4
5b
6
7b
8
9
10b
11
12b
13
14b
15
16
17
18
19
20 
FV/PEOT
c
Day
-28 to -1
1
2
8d
(± 2 
days)
9
15d
(± 2 
days)
16
22d
(± 2 days)
29d
(± 2 
days)
30
36d
(± 2 
days)
37
43d
(± 2 
days)
44
50
57
64
78
92
99
(± 2 days)
(± 2 days)
measurementt
Headache questionnaireu
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Stool sample assessmentv
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject exit interview
X
AE=adverse event; BAFF=B-cell activating factor; BL=Baseline; BP=blood pressure; CSF=cerebrospinal fluid; CT=computed tomography; DNA=deoxyribonucleic acid; 
ECG=electrocardiogram; FV=Final Visit; GI=gastrointestinal; HIV=human immunodeficiency virus; IgA=immunoglobulin A; IgE=immunoglobulin E; IgG=immunoglobulin G; 
IGRA= interferon-gamma release assay; IgM=immunoglobulin M; IMP=investigational medicinal product; IRT=interactive response technology; LP=lumbar puncture; 
MG=myasthenia gravis; MGADL=myasthenia gravis-Activities of Daily Living; MGFA=Myasthenia Gravis Foundation of America; MRI=magnetic resonance imaging; 
PEOT=premature end of treatment; PK=pharmacokinetics; PR=pulse rate; RNA=ribonucleic acid; QMG=Quantitative Myasthenia Gravis; 
 
 SFEMG=single fiber electromyogram; TB=tuberculosis; UV=Unscheduled Visit
a Subjects will return to the clinic/hospital for Visits 15, 16, 18, and 20; for Visits 17 and 19 subjects will either return to the clinic/hospital, or, if possible and 
agreed by both the investigator and subject, have home visits conducted by certified healthcare professionals.
b This visit is a telephone contact 24 hours post-IMP dose start.
c Subjects who withdraw early will be encouraged to complete the PEOT Visit plus the FV (approximately 8 weeks after the final study drug administration).
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 Includes consent for jitter (SFEMG) for the subjects consenting to this measurement at the participating sites. Additional informed consent is needed for 
participation in the exploratory genomic substudy.
f Systolic and diastolic BP, pulse rate, temperature, and respiratory rate. On dosing days, vital signs will be measured prior to IMP administration, 15 minutes 
after the start of the infusion, at the end of the infusion, 2 hours after the end of infusion and 4 hours after the end of the infusion. At nondosing visits, vital 
signs need only be taken once during the visit.
g Body weight at Screening and at Visit 9 will be used for calculation of dose; height will be assessed only at Screening.
h In addition to Screening and the FV, a full neurological examination should be performed for any subject who experiences severe headache.
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i A query for suicidal ideation will be asked by Investigator at each clinical visit (including Visit 17 or Visit 19 when it is conducted at the clinic). A full 
Columbia Suicide Severity Rating Scale (C-SSRS) assessment will be performed only when subject has a positive response to the suicidal ideation query. If a 
subject has active suicidal ideation as confirmed by the answer ‘Yes’ to Question 4 or Question 5 of the C-SSRS assessments, the subject will be excluded or
withdrawn from the study and immediately referred to a Mental Healthcare Professional.
j ECGs will be read by a central reader.
k The IGRA test will be performed in a central laboratory. Subject should not be dosed until IGRA result is available and negative.
l Pre- and postdose at Visits 2, 4, 6, 9, 11, and 13; postdose samples are to be taken 4 hours after the infusion has ended.
m Blood sample to be taken prior to dosing of IMP.
n Urine pregnancy test will be performed using a dipstick test; a positive urine pregnancy test must be confirmed using a serum pregnancy test.
o Sampling will be performed predose at Visit 2 and 4 hours postdose at Visits 2, 4, 6, 9, 11 and 13. A sample will be obtained at Visit 20.  
p Sampling for exploratory safety biomarkers at Baseline (Visit 2) and 4 hours post dosing (Visit 2) for all subjects. During follow up only in subjects with severe 
headache and/or moderate to severe GI disturbances.
q Sampling will be performed pre- and 4 hours postdose at Visits 2, 6, 9 and 13. A sample will be obtained at Visit 20. Samples will be obtained at Visits 4 and 
11 for subjects with an infusion reaction.
r This assessment will be performed at the clinic/hospital. If the subject has a home visit with certified health professionals at Visit 17 and Visit 19, this 
assessment will not be performed.
s Subjects should not take pyridostigmine (or any
 medication) from midnight before testing when medically safe to do so 
to standardize testing, but if not medically appropriate, then the treatment can be continued but the testing should be performed as best as possible at the same 
timeframe post last any 
 inhibitor dosing for each evaluation during the study.
u 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.
v 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.
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Change #6
6.1 Inclusion Criteria 
4. Subject would currently be considered for treatment with immunological therapy such as 
IVIG/PLEX by the investigator.
5. Subject has a well-documented presence (current or historical) evidence in his/her medical 
history or at Screening of detectable autoantibodies (
).
Has been changed to:
4. Subject would currently be considered for treatment with immunological therapy (eg 
IVIG/PLEX) by the investigator.
5. Subject has a well-documented record of autoantibodies against 
 prior to 
Visit 1 (Screening).
Change #7
6.2.2
Exclusion criteria related to concomitant medications/procedures
30. Subject had a thymectomy in the past 6 months, a history of thymoma World Health 
Organization grade B2 or B3, or Masaoka grade III or IV, or history of a thymoma requiring 
chemotherapy and/or radiotherapy.
Has been changed to:
30. Subject had a thymectomy in the past 6 month or a thymoma at any time that required 
chemotherapy and/or radiotherapy.
Change #8
6.4 Withdrawal Criteria
Changes to criterions #1 and #5.
Subjects MUST be withdrawn from IMP if any of the following events occur:
1. 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 adverse event (AE) of GI disturbance or headache which is 
considered related to the IMP in the opinion of the investigator.
5. Subject received IVIg or PLEX during the Treatment Period.
Has been changed to:
Subjects MUST discontinue IMP if any of the following events occur:
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1. 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 adverse event (AE) of GI disturbance or severe headache 
which is considered related to the IMP in the opinion of the investigator.
5. Subject received prohibited concomitant medications (as defined in Section 7.8.2 of this 
protocol) during the Treatment Period.
Change #9
7.8.1 Permitted concomitant medications
Table 7.1 lists the concomitant medications that are permitted during the course of the study at a 
stable dose.
Table 7.1:
Permitted concomitant treatments
Permitted 
Medications
Dose
Comment
Oral Corticosteroids 
(eg, prednisolone)
-
Methotrexate
≤30mg/week
Mycophenolate mofetil
≤3g/day
Cyclosporin
≤5mg/day
Azathioprine
≤3mg/kg/day
Cholinesterase 
inhibitors
≤600mg 
Pyridostigmine/day
Tacrolimus
3mg/day
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Has been changed to:
Table 7.1 lists the concomitant medications that are permitted during the course of the study at a 
stable dose.
Table 7.1:
Permitted concomitant treatments
Permitted 
Medications
Dose
Comment
Oral Corticosteroids 
(eg, prednisolone)
-
Methotrexate
≤30mg/week
Mycophenolate 
mofetil
≤3g/day
Cyclosporina
≤5mg/kg/day for 
unmodified
≤4mg/kg/day for modified 
(microemulsion)
Azathioprine
≤3mg/kg/day
Cholinesterase 
inhibitors
≤600mg 
Pyridostigmine/day
Tacrolimusb
≤5mg/day
a Doses higher than listed are permissible if trough level is ≤300ng/L.
b If the total daily weight-based dose is >5mg, then a plasma trough level should be checked to 
ensure subject is not above the recommended therapeutic range.
Change #10
7.8.2
Prohibited concomitant treatments (medications and therapies)

Medications which could interfere with the function of the NMJ (and which therefore could 
impair subjects with MG), such as, but not limited to, the following medications. For a more 
detailed list please refer to the Study Procedures Manual.
Has been changed to:

Medications which could interfere with the function of the NMJ (and which therefore could 
impair subjects with MG), such as, but not limited to, the following medications. For a more 
detailed list please refer to the MGFA medication list 
(http://www.myasthenia.org/LivingwithMG/DrugstoAvoid.aspx).
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Change #11
9.3
Patient-reported outcomes
Subjects will complete 3 patient-reported outcomes (PROs) and participate in 1 subject exit 
interview as per time points mentioned in the schedule of study assessments in Section 5.2. 
Study personnel other than the treating physician should administer the PROs. The PROs should 
be completed by the subject themselves in a quiet place.
The PROs and the subject exit interview should be completed in the following order: MG muscle 
weakness and fatigability, Fatigue, and MGADL, followed by the subject exit interview (which 
will be performed only at the FV). The PROs should only be checked for completeness. On 
dosing days, the PROs will be completed prior to dosing
Has been changed to:
Subjects will complete 4 patient-reported outcomes (PROs) and participate in 1 subject exit 
interview as per time points mentioned in the schedule of study assessments in Section 5.2. 
Study personnel other than the treating physician should administer the PROs. The PROs should 
be completed by the subject themselves in a quiet place.
The PROs and the subject exit interview should be completed in the following order: MG muscle 
weakness and fatigability, Fatigue, MGADL and MGII, followed by the subject exit interview 
(which will be performed only at the FV). The PROs should only be checked for completeness. 
On dosing days, the PROs will be completed prior to dosing.
Change #12
Additional subsection:
9.3.4
Myasthenia Gravis Index Impairment
The MGII is a measure of disease severity based on the signs and symptoms of Myasthenia 
Gravis patients (Appendix 18.6). It was developed using a patient-centered approach and 
following current guidelines for outcome measure development, incorporating patient input 
throughout the different development phases (Barnett et al, 2014, Barnett et al, 2016). The MGII 
has 22 patient-reported and 6 examination items, and scores are presented as a sum of all items 
for a total score but also as an ocular and generalized sub-score.
The MGII has shown construct validity and reliability in an outpatient setting. It has less floor 
effect compared to other commonly used outcome measures, and it can effectively discriminate 
among patients with different degrees of severity (Barnett et al, 2016). Finally, the MGII is 
sensitive to detect clinical change after interventions, and most importantly it can detect patient-
meaningful change. Additionally, the MGII showed more relative efficiency than the QMGS, 
MGC and MG-ADL to detect change in short-term interventions for Myasthenia. Estimates for 
the minimal important difference were developed.
Change #13
9.5
Single Fiber Electromyography
At participating sites, subjects consenting to SFEMG measurement should not take 
pyridostigmine from midnight before testing when medically safe to do so to standardize testing, 
but if not medically appropriate, then the treatment can be continued but the testing should be 
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QMG, MG-Composite, and MGADL responder rates at each assessed post-Randomization Visit 
(during Dosing Period 1) will be compared between the 2 Treatment Groups utilizing Fisher’s 
exact test.
The percentage of subjects with each MGFA classification at each scheduled assessment during 
Treatment and Observation Periods will be calculated.
Psychometric analyses of the newly developed measures MG muscle weakness severity and 
fatigability and fatigue scales will be performed blinded from treatment arms. The association 
between PROs and clinical variables will also be explored, as well as the association between the 
various PROs. A psychometric analysis of the MG muscle weakness severity and fatigability 
scale and fatigue scale using Rasch analysis will be performed, but reported separately from the 
CSR.
Changes in SFEMG will be summarized using descriptive statistics, by treatment group and time 
point, including changes from Baseline
Has been changed to:
The secondary variables and change from Baseline in QMG score, MG-Composite score, 
MGADL score, MGII score, muscle weakness severity and fatigability scale score and fatigue 
scale score, at each assessed post Randomization Visit (during Dosing Period 1 including Visit 
9) will also be analyzed utilizing the MMRM approach similarly to the change from Baseline in 
QMG for the FAS as described in Section 14.3.1.
QMG, MG-Composite, and MGADL responder rates at each assessed post-Randomization Visit 
(during Dosing Period 1) will be compared between the 2 Treatment Groups utilizing Fisher’s 
exact test.
The percentage of subjects with each MGFA classification at each scheduled assessment during 
Treatment and Observation Periods will be calculated.
Psychometric analyses of the newly developed measures MG muscle weakness severity and 
fatigability and fatigue scales will be performed blinded from treatment arms. The association 
between PROs and clinical variables will also be explored, as well as the association between the 
various PROs. A psychometric analysis of the MG muscle weakness severity and fatigability 
scale and fatigue scale using Rasch analysis will be performed, but reported separately from the 
CSR.
Changes in MCD of the IPI, and normal fiber pairs in jitter (SFEMG) will be summarized using 
descriptive statistics, by treatment group and time point, including changes from Baseline. A 
reduction in MCD of ≥9µs in jitter (SFEMG) studies will also be summarized using descriptive 
statistics, by treatment group and time point, including changes from Baseline.
Change #16
14.4.4 Immunological variables
All immunological variables including concentrations of Igs (IgA, IgE, and IgM), serum 
complement levels (C3 and C4) and plasma complement levels (C3a and C5a), and serum BAFF 
will be listed and summarized, using descriptive statistics, by Treatment Group and visit 
including changes from Baseline. Concentrations of cytokines will be listed and summarized if 
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there are sufficient data. Figures of mean values and changes from Baseline of immunological 
variables may be presented, and will be described in the SAP.
The 
 status (negative/positive) and changes in relative mass units from Baseline will be 
listed and summarized by treatment group.
The 
 antibodies will be listed and summarized by 
treatment group.
Has been changed to:
All immunological variables including concentrations of Igs (IgA, IgE, and IgM), serum 
complement levels (C3 and C4) and plasma complement levels (C3a and C5a), and serum BAFF 
will be listed and summarized, using descriptive statistics, by Treatment Group and visit 
including changes from Baseline. Concentrations of cytokines will be listed and summarized if 
there are sufficient data. Figures of mean values and changes from Baseline of immunological 
variables may be presented, and will be described in the SAP.
The 
 status (negative or confirmed positive) and either changes in relative mass units from 
Baseline for all scheduled assessments or titres for those confirmed positive will be listed and 
summarized by treatment group.
The 
 antibodies will be listed and summarized by 
treatment group.
Change #17
Additional in-text references:
17
References
Barnett C, Bril V, Kapral M, Kulkarni A, Davis AM. A conceptual framework for evaluating 
impairments in myasthenia gravis. PLos One. 2014;9(5).
Barnett C, Bril V, Kapral M, Kulkarni A, Davis AM Development and validation of the 
Myasthenia Gravis Impairment Index. Neurology. 2016; 87(9): 879–886.
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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
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.
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SAP_003.pdf: 
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Statistical Analysis Plan 
UCB7665 
MG0002 
 
 
 
Confidential 
Page 1 of 70 
 
STATISTICAL ANALYSIS PLAN  
Study: MG0002 
Product: UCB7665 
A MULTICENTER, RANDOMIZED, INVESTIGATOR- AND SUBJECT-BLIND, 
PLACEBO-CONTROLLED, TREATMENT SEQUENCE STUDY EVALUATING THE 
SAFETY, TOLERABILITY, AND EFFICACY OF UCB7665 IN SUBJECTS WITH 
MODERATE TO SEVERE MYASTHENIA GRAVIS 
 
SAP/Amendment Number Date 
Final SAP 
20 Dec 2017 
Final SAP amendment 1 
20 Jun 2018 
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. 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... 6 
1 
INTRODUCTION ........................................................................................................... 12 
2 
PROTOCOL SUMMARY ............................................................................................... 12 
2.1 Study objectives ............................................................................................................... 12 
2.1.1 
Primary objective ................................................................................................. 12 
2.1.2 
Secondary objectives ........................................................................................... 12 
2.1.3 
Exploratory Objectives ........................................................................................ 13 
2.2 Study variables ................................................................................................................. 13 
2.2.1 
Efficacy variables ................................................................................................ 13 
2.2.1.1 
Primary efficacy variable .......................................................................... 13 
2.2.1.2 
Secondary efficacy variables ..................................................................... 13 
2.2.1.3 
Other efficacy variables ............................................................................. 14 
2.2.2 
Other and exploratory variables ........................................................................... 14 
2.2.2.1 
Safety variables ......................................................................................... 14 
2.2.2.2 
Pharmacokinetic variable .......................................................................... 15 
2.2.2.3 
Pharmacodynamic variables ...................................................................... 15 
2.2.2.4 
Immunological variables ........................................................................... 15 
2.3 Study design and conduct ................................................................................................ 16 
2.4 Determination of sample size ........................................................................................... 18 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 18 
3.1 General presentation of summaries and analyses ............................................................ 18 
3.2 General study level definitions ........................................................................................ 20 
3.2.1 
Analysis time points ............................................................................................ 20 
3.2.1.1 
Relative day ............................................................................................... 20 
3.2.2 
Study periods ....................................................................................................... 20 
3.2.3 
Mapping of assessments performed at Premature End of Treatment Visit ......... 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 
Randomized Set ................................................................................................... 23 
3.5.3 
Safety Set ............................................................................................................. 23 
3.5.4 
Full Analysis Set .................................................................................................. 23 
3.5.5 
Per Protocol Set ................................................................................................... 23 
3.5.6 
Pharmacokinetic Per-Protocol Set: ...................................................................... 24 
3.5.7 
Pharmacodynamic Per-Protocol Set: ................................................................... 24 
3.6 Treatment assignment and treatment groups ................................................................... 24 
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3.7 Center pooling strategy .................................................................................................... 24 
3.8 Coding dictionaries .......................................................................................................... 24 
3.9 Changes to protocol-defined analyses.............................................................................. 25 
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 ............................................................................... 26 
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 .............................................................................. 29 
4.5 Multicenter studies ........................................................................................................... 29 
4.6 Multiple comparisons/multiplicity ................................................................................... 29 
4.7 Use of an efficacy subset of subjects ............................................................................... 29 
4.8 Active-control studies intended to show equivalence ...................................................... 29 
4.9 Examination of subgroups ............................................................................................... 29 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 29 
5.1 Subject disposition ........................................................................................................... 29 
5.2 Protocol deviations ........................................................................................................... 30 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 30 
6.1 Demographics .................................................................................................................. 30 
6.2 Other Baseline characteristics .......................................................................................... 31 
6.3 Medical history and concomitant diseases ....................................................................... 31 
6.4 Past, prior and concomitant medications ......................................................................... 31 
6.4.1 
Past medication definition ................................................................................... 32 
6.4.2 
Prior medication definition .................................................................................. 32 
6.4.3 
Concomitant medication definition ..................................................................... 32 
6.4.4 
Assignment of medications to study period ......................................................... 32 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 32 
8 
EFFICACY ANALYSES ................................................................................................ 33 
8.1 Statistical analysis of the primary efficacy variable ........................................................ 33 
8.1.1 
Derivations of primary efficacy variable ............................................................. 33 
8.1.2 
Primary analysis of the primary efficacy variable ............................................... 33 
8.1.3 
Supportive and sensitivity analyses of the primary efficacy variable ................. 33 
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8.2 Statistical analysis of the secondary efficacy variables ................................................... 34 
8.2.1 
MG-composite score ............................................................................................ 34 
8.2.2 
MG activities of daily living ................................................................................ 35 
8.3 Analysis of other efficacy variables ................................................................................. 35 
8.3.1 
Summaries of efficacy variables .......................................................................... 35 
8.3.2 
Muscle weakness severity and fatigability scale ................................................. 35 
8.3.3 
Fatigue Instrument ............................................................................................... 36 
8.3.4 
MGFA Clinical Classification ............................................................................. 36 
8.3.5 
MG Impairment Index ......................................................................................... 36 
8.3.6 
Responder rates .................................................................................................... 37 
8.3.7 
Single Fiber Electromyogram .............................................................................. 37 
8.3.8 
Correlation analysis ............................................................................................. 38 
8.3.9 
Psychometric analyses ......................................................................................... 38 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS .......................................... 38 
9.1 Pharmacokinetics ............................................................................................................. 38 
9.2 Pharmacodynamics .......................................................................................................... 38 
9.2.1 
Total serum IgG and IgG subclasses ................................................................... 39 
9.2.2 
MG-specific autoantibodies ................................................................................. 39 
10 IMMUNOLOGICAL ANALYSES ................................................................................. 39 
10.1 Immunoglobulins ............................................................................................................. 39 
10.2 
 ........................................................................................................ 39 
10.3 Serum complement levels and plasma complement levels .............................................. 41 
10.4 Serum BAFF levels .......................................................................................................... 41 
10.5 Cytokines ......................................................................................................................... 41 
10.6 
 antibodies ................................................... 41 
11 SAFETY ANALYSES ..................................................................................................... 42 
11.1 Extent of exposure ........................................................................................................... 42 
11.2 Adverse events ................................................................................................................. 43 
11.3 Clinical laboratory evaluations ........................................................................................ 45 
11.3.1 
Potential drug-induced liver injury ...................................................................... 46 
11.4 Vital signs, physical findings, and other observations related to safety .......................... 46 
11.4.1 
Vital signs ............................................................................................................ 46 
11.4.2 
Electrocardiograms .............................................................................................. 47 
11.4.3 
Exploratory safety biomarkers ............................................................................. 47 
11.4.4 
Physical examination ........................................................................................... 48 
11.4.5 
Other safety variable ............................................................................................ 48 
12 OTHER ANALYSES ...................................................................................................... 48 
13 REFERENCES ................................................................................................................ 50 
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14 APPENDICES ................................................................................................................. 51 
14.1 Quantitative myasthenia gravis testing form ................................................................... 51 
14.2 MG-composite score ........................................................................................................ 52 
14.3 MG-Activities of Daily Living ........................................................................................ 53 
14.4 MG muscle weakness and fatigability ............................................................................. 54 
14.5 MG-Impairment Index ..................................................................................................... 57 
14.6 TEMA/PCS criteria for Rozanolixizumab program ........................................................ 63 
15 AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP) (IF 
APPLICABLE) ................................................................................................................ 66 
15.1 Amendment 1 ................................................................................................................... 66 
15.1.1 
Rationale for the amendment ............................................................................... 66 
15.1.2 
Specific changes: ................................................................................................. 66 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ..................................................... 70 
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LIST OF ABBREVIATIONS 
ACP 
above cut-point 
 
 
ADaM 
Analysis Data Model 
AE 
adverse event 
ALC 
absolute lymphocyte count 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANT 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
ALQ 
above the limit of quantification 
ANCOVA 
analysis of covariance 
  
 
  
 
AST 
aspartate aminotransferase 
BAFF 
B-cell activating factor 
BCP 
below cut-point 
BLQ 
below the limit of quantification 
BMI 
body mass index 
BUN 
blood urea nitrogen 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
confidence interval 
CP 
confirmed positive 
CRO 
Contract Research Organization 
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CSF 
cerebral spinal fluid 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMC 
Data Monitoring Committee 
DEM 
Data Evaluation Meeting 
ES 
Enrolled Set 
EudraCT 
European Union Drug Regulating Authorities 
Clinical Trials 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
geoCV 
geometric coefficient of variation 
geoMean 
geometric mean 
GGT 
gamma-glutamyltransferase 
GI 
gastrointestinal 
HbA1c 
glycosylated hemoglobin 
HBsAG 
hepatitis B surface Antigen 
HCV Ab 
hepatitis C virus antibody 
HDL 
high density lipoprotein 
HIV 
human immunodeficiency virus 
HLT 
high level term 
hsCRP  
high sensitivity C-reactive protein 
ICH 
International Council for Harmonisation 
Ig 
immunoglobulin 
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IgA 
immunoglobulin A 
IgE 
immunoglobulin E 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IGRA 
interferon-gamma release assay 
IMP 
investigational medicinal product 
IPD 
important protocol deviation 
IPI 
interpotential interval 
LDH 
low density lipoprotein 
LLOQ 
lower limit of quantification 
LOCF 
last observation carried forward 
LP 
lumbar puncture 
LS 
least squares 
MCD 
mean consecutive difference 
MedDRA 
Medical Dictionary for Regulatory Activities 
MG 
myasthenia gravis 
MGADL 
myasthenia gravis-Activities of Daily Living 
MGFA 
Myasthenia Gravis Foundation of America 
MGII 
Myasthenia Gravis Impairment Index 
MMRM 
mixed model repeated measures 
MRI 
magnetic resonance imaging 
NCP 
not confirmed positive 
PCS 
potentially clinically significant 
PD 
pharmacodynamic(s) 
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PDILI 
potential drug-induced liver injury 
PD-PPS 
Pharmacodynamic Per-Protocol-Set 
PEOT 
Premature End of Treatment Visit 
PK 
pharmacokinetic(s) 
PK-PPS 
Pharmacokinetic Per Protocol Set 
PPS 
Per Protocol Set 
PRO 
Patient Reported Outcome 
PT 
preferred term 
QMG 
quantitative myasthenia gravis 
QTcB 
QT corrected for heart rate using Bazett’s formula 
QTcF 
QT corrected for heart rate using Fridericia’s 
formula 
RBC 
red blood cell 
RS 
Randomized Set 
SAP 
Statistical Analysis Plan 
sc 
subcutaneous 
SD 
Standard Deviation 
SFEMG 
single fiber electromyography 
SS 
Safety Set 
SOC 
system organ class 
TFL 
Tables, figures and listings 
TEAE 
treatment-emergent adverse event 
TEMA 
treatment-emergent markedly abnormal 
ULN 
upper limit of normal 
WBC 
white blood cell 
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WHODD 
World Health Organization Drug Dictionary 
 
 
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LIST OF TABLES 
Table 3‒1: 
Expected Baseline Visits.................................................................................. 21 
Table 4‒1: 
Calculation rules for duration of AEs .............................................................. 27 
Table 11‒1: 
Clinical laboratory measurements.................................................................... 45 
Table 14‒1: 
Quantitative myasthenia gravis testing form ................................................... 51 
Table 14‒2: 
MG-composite score items and scoring algorithm .......................................... 52 
Table 14‒3: 
MG-Activities of Daily Living ........................................................................ 54 
Table 14‒4: 
MG muscle weakness PRO .............................................................................. 54 
Table 14‒5: 
MG Symptom Fatigability ............................................................................... 56 
Table 14‒6: 
MG Impairment Index ..................................................................................... 58 
Table 14-7: 
TEMA/PCS  Values for Rozanolixizumab Clinical Development Program 
Based on CTCAE Grades ................................................................................ 63 
 
 
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1 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide all information that is necessary 
to perform the required statistical analysis of MG0002. 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 study documents: 
1. Final Protocol: 21 Oct 2016 
2. Protocol Amendment 1: 07 Feb 2017 
3. Protocol Amendment 2: 15 Sep 2017 
Unless specified below, the study will be analyzed as described in the most recent version of the 
protocol/amendment (European Union Drug Regulating Authorities Clinical Trials 
[EudraCT]-Number: 2016-002698-36). 
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP will be amended accordingly. If, after database lock, additional analyses are 
required to supplement the planned analyses described in this SAP, those unplanned analyses 
will not be described in an amended SAP but they will be described in a separate statistical 
analysis plan. However, if analysis definitions have to be modified or updated, a SAP 
amendment will be required. 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 International is the Contract Research 
Organization (CRO) for this study. 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
The primary objective of the study is: 
 To evaluate the clinical efficacy of UCB7665 as a chronic-intermittent treatment in subjects 
with generalized myasthenia gravis (MG) who are classified as moderate to severe 
2.1.2 
Secondary objectives 
The secondary objectives of the study are: 
 To gather data for future study planning, whether for chronic-intermittent treatment or a 
longer therapy option by evaluating the general concept that UCB7665 has a clinical effect in 
patients with generalized MG 
 To evaluate the safety and tolerability of UCB7665 administered by subcutaneous (sc) 
infusion in subjects with MG 
 To assess the effect of UCB7665 as measured by total Immunoglobulin G (IgG) 
concentrations in serum 
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2.1.3 
Exploratory Objectives 
The exploratory objectives are: 
 To assess the effect of UCB7665 on MG-specific autoantibodies (
 
 levels in serum 
 To evaluate the effects of UCB7665 on the concentration of IgG subclasses, immunoglobulin 
M (IgM), immunoglobulin A (IgA), and immunoglobulin E (IgE), and serum and plasma 
complement levels 
 To evaluate the effect of UCB7665 on B-cell activating factor (BAFF) and on cytokines (in 
all subjects) 
 To evaluate the effect of UCB7665 on cytokines in subjects experiencing infusion reactions 
 To evaluate the emergence of 
 with respect to immunogenicity and 
Pharmacokinetics/Pharmacodynamics (PK/PD) 
 To evaluate the effect of UCB7665 on clinical electrophysiological parameters of 
neuromuscular transmission in a subset of subjects 
 To assess the plasma concentrations of UCB7665 administered by sc infusion 
 To evaluate the effects of UCB7665 on blood biomarkers for safety (including, but not 
limited to 
 
) only in subjects with severe headache and/or moderate to severe 
gastrointestinal (GI) disturbance 
 The effects of UCB7665 on 
 antibodies 
 To evaluate peripheral blood biomarkers in relation to disease etiology, progression and 
treatment outcome 
 To evaluate the genomic components of MG to understand the molecular etiology, 
progression, and treatment of the disease, applicable only for subjects consenting to 
participate in the optional genomic analyses substudy 
2.2 
Study variables 
2.2.1 
Efficacy variables 
2.2.1.1 
Primary efficacy variable 
The primary efficacy variable is: 
 Change from Baseline in quantitative myasthenia gravis (QMG) score to Visit 9 (Day 29) 
2.2.1.2 
Secondary efficacy variables 
The secondary efficacy variables are: 
 Change from Baseline in MG-Composite score to Visit 9 (Day 29) 
 Change from Baseline in myasthenia gravis-Activities of Daily Living (MGADL) score to 
Visit 9 (Day 29) 
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2.2.1.3 
Other efficacy variables 
The other efficacy variables are: 
 Value and change from Baseline in QMG at each scheduled assessment during Treatment 
and Observation Periods 
 QMG responder (≥3.0 point improvement from Baseline) at each scheduled assessment 
during Treatment and Observation Periods 
 Value and change from Baseline in MG-Composite score at each scheduled assessment 
during Treatment and Observation Periods 
 MG-Composite responder (≥3.0 point improvement from Baseline) at each scheduled 
assessment during Treatment and Observation Periods 
 Value and change from Baseline in MGADL at each scheduled assessment during Treatment 
and Observation Periods 
 MGADL responder (≥3.0 point improvement from Baseline) at each scheduled assessment 
during Treatment and Observation Periods 
 Myasthenia Gravis Foundation of America (MGFA) classification at each scheduled 
assessment during Treatment and Observation Periods 
 Value and change from Baseline in MG muscle weakness and fatigability at each scheduled 
assessment during Treatment and Observation Periods 
 Value and change from Baseline in fatigue at each scheduled assessment during Treatment 
and Observation Periods 
 Value and change from Baseline in Myasthenia Gravis Impairment Index (MGII) scores at 
each scheduled assessment during Treatment and Observation Periods 
 Value and change from Baseline in MGII ocular sub-scores at each scheduled assessment 
during Treatment and Observation Periods 
 Value and change from Baseline in MGII generalized domain sub-scores at each scheduled 
assessment during Treatment and Observation Periods 
 Change in the percentage of normal fiber pairs in jitter [single fiber electromyography 
(SFEMG)] studies from Baseline to Visit 9 for the subjects consenting to this measurement at 
the participating sites 
 Change in mean consecutive difference (MCD) of the interpotential interval (IPI) in jitter 
(SFEMG) studies from Baseline to Visit 9 for the subjects consenting to this measurement at 
the participating sites 
 A reduction in MCD of ≥9μs in jitter (SFEMG) studies will define clinically meaningful 
improvement 
2.2.2 
Other and exploratory variables 
2.2.2.1 
Safety variables 
The safety variables are the following: 
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 Occurrence of treatment-emergent adverse events (TEAEs) 
 Vital sign values and changes from Baseline (systolic and diastolic BP, temperature, pulse 
rate, respiratory rate, and body weight) at each scheduled assessment during Treatment and 
Observation Periods 
 12-lead ECG values and change from Baseline at each scheduled assessment during 
Treatment and Observation Periods 
 Laboratory values and changes from Baseline at each scheduled assessment during 
Treatment and Observation Periods (hematology, clinical chemistry, and urinalysis) 
 Change from Baseline in exploratory safety biomarkers (may include but not limited to 
 
) in subjects with severe headache and/or moderate to severe GI disturbance 
 TEAEs leading to withdrawal of investigational medicinal product (IMP) 
The clinical safety laboratory tests are detailed in Table 11‒1. 
2.2.2.2 
Pharmacokinetic variable 
The PK variable is the following: 
 Plasma concentration of UCB7665 at each scheduled assessment during Treatment and 
Observation Periods 
2.2.2.3 
Pharmacodynamic variables 
The PD variables are the following: 
 Minimum value and maximum (absolute and percentage) decrease from Baseline in total 
serum IgG concentration during the study 
 Value and change (absolute and percentage) from Baseline in total serum IgG concentrations 
at each scheduled assessment during Treatment and Observation Periods 
 Value and change (absolute and percentage) from Baseline in serum IgG subclass 
concentrations at each scheduled assessment during Treatment and Observation Periods 
 Change in MG-specific autoantibody
levels in serum from Baseline 
at each scheduled assessment during Treatment and Observation Periods 
2.2.2.4 
Immunological variables  
The other immunological variables are the following: 
 Change from Baseline in serum immunoglobulin (Ig) concentrations (total IgA, IgE, and 
IgM) at each scheduled assessment during Treatment and Observation Periods 
 Change from Baseline in serum complement levels (C3 and C4) and plasma complement 
levels (C3a and C5a) predose at Visit 2 and 4 hours postdose at each scheduled assessment 
during Treatment and Observation Periods 
 
 (
) status (negative or confirmed positive) and either change 
from Baseline in relative mass units at each scheduled assessment during Treatment and 
Observation Periods or titre for those confirmed positive 
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 Change from Baseline in serum BAFF levels 
 Change from Baseline in cytokines pre- and postdose (postdose - in subjects experiencing 
infusion reactions) at assessments during Treatment and Observation Periods 
 Change from Baseline in 
antibodies 
 Change from Baseline in exploratory biomarkers relating to mechanism of action, disease 
activity, treatment response, and clinical outcome 
2.3 
Study design and conduct 
This is a Phase 2a, multicenter, randomized, investigator- and subject-blind, placebo controlled, 
2-arm, repeat dose, treatment sequence study evaluating the safety and efficacy of UCB7665 as a 
chronic-intermittent treatment for subjects with moderate to severe generalized MG. 
Approximately 42 randomized subjects will be enrolled at approximately 30 sites from Europe, 
United States of America (USA), and Canada to achieve the targeted number of 40 evaluable 
subjects. 
The maximum duration of the study per subject is approximately 18 weeks, consisting of a 
Screening Period (1 to 28 days), Treatment Period (6 weeks), and an Observation Period 
(8 Weeks).  
Screening Period: The purpose of the Screening Period is to evaluate and confirm the subject’s 
eligibility. The Screening Period should not exceed 28 days in total. 
Treatment Period: The Treatment Period will consist of Dosing Period 1 followed by Dosing 
Period 2. Subjects will receive 3 doses of IMP at weekly intervals during each Dosing Period as 
follows. 
 Dosing Period 1 will be 4 weeks, with 2 parallel Treatment Groups (UCB7665 7mg/kg or 
placebo). 
 Dosing Period 2 will be 2 weeks, with 2 parallel Treatment Groups (UCB7665 7mg/kg or 
UCB7665 4mg/kg). 
Prior to receiving an infusion with IMP, subjects will be assessed for efficacy measurements at 
each visit in the Treatment Period. All safety and efficacy measurements must follow the order 
specified in the Study Procedures Manual. 
Dosing Period 1: Dosing Period 1 will last for approximately 4 weeks (Day 1 to Day 28) and 
includes Visits 2, 3, 4, 5, 6, 7, and 8. Following completion of the Screening Period, eligible 
subjects will check-in at the clinic/hospital for the Randomization Visit (Visit 2). Subjects who 
continue to meet eligibility requirements will be randomized 1:1 to receive 7mg/kg of UCB7665 
or placebo, administered by an approximately 30 minute sc infusion at weekly intervals for 3  
weeks (Visits 2, 4, and 6) followed by an assessment visit at Week 4 (Visit 8). At Visits 2, 4, and 
6 in Dosing Period 1, subjects will be required to remain in the clinic/hospital for at least 4 hours 
for safety monitoring after the infusion. Subjects may leave the clinic/hospital once the safety 
monitoring postdose period is over and the investigator or designee has no safety concerns. A 
follow-up telephone call will be conducted 24 hours postdose to assess the status of the subject 
(Visits 3, 5, and 7). Subjects will return to the clinic/hospital at Visit 8 for safety and efficacy 
assessments. The primary efficacy endpoint, change from Baseline in the QMG score, will be 
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assessed at the beginning of Dosing Period 2 at Visit 9 (Day 29) prior to rerandomization . The 
efficacy assessments that are performed at Visit 9 will therefore occur 2 weeks after the final 
dose of study drug in Dosing Period 1. 
Dosing Period 2: Dosing Period 2 will last for approximately 2 weeks (Day 29 to Day 43) and 
includes Visit 9, 10, 11, 12, 13, and 14. Subjects will return to the clinic for Visit 9, 11, and 13 
for safety and efficacy assessments. At Visit 9, following the administration of safety and 
efficacy assessments, subjects initially randomized at Baseline to placebo or to 7mg/kg of 
UCB7665 will be rerandomized 1:1 to receive either 3 doses of 7mg/kg or 3 doses of 4mg/kg 
administered by a 30 minute sc infusion at weekly intervals (Visit 9, 11, and 13). The interactive 
response technology (IRT) will stratify the rerandomization based on the treatment received in 
Dosing Period 1. At each weekly clinic visit in Dosing Period 2 (Visits 9, 11, and 13), subjects 
will be required to remain in the clinic/hospital for at least 4 hours safety monitoring postdose 
period as determined. Subjects may leave the clinic/hospital once the safety monitoring postdose 
period is over and the investigator or designee has no safety concerns. A follow-up telephone call 
will be conducted 24 hours post dose to assess the status of the subject (Visits 10, 12, and 14). 
Observation Period: All subjects must be followed for 8 weeks after the final dose of IMP is 
administered. Subjects will return to the clinic for Visits 15, 16, and 18 for efficacy and for 
safety assessments. Subjects will either return to the clinic/hospital, or, if possible and agreed by 
investigator and subject, have home visits conducted by certified healthcare professionals, for 
Visits 17, 19, and 20. The Observation Period begins the day after the final dose of IMP (ie, Visit 
13, Day 43); Visit 15 (Day 50) is the first visit in the Observation Period. 
Figure 2‒1 presents a schematic diagram of the study design. 
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Figure 2‒1: Schematic diagram 
 
2.4 
Determination of sample size 
The primary efficacy endpoint of this study is change in QMG score from Baseline to Visit 9 
(Day 29). 
The sample size calculation use a 1-sided 
 significance level, an estimate (based on a 
 
Confidence Interval [CI]) of the Standard Deviation (SD) for change in QMG of 
 and an 
anticipated treatment effect of 
 (Zinman et al, 2007). 
Assuming a treatment difference of 
 points in the mean change from Baseline in QMG at 
Visit 9 between the placebo and UCB7665 treatment arm with SD equal to 
, a sample size of 
 subjects (
 for each treatment group) provides >90% power to detect a treatment difference. 
Further it will be assumed that 
 of the randomized subjects cannot be utilized 
for the Full Analysis Set (FAS) and, hence 
 subjects will be randomized. 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical evaluation will be performed by PAREXEL. Analysis Data will adhere to CDISC 
(Clinical Data Interchange Standards Consortium) guidance documents for Analysis Data Model 
(ADaM) and follow their UCB interpretation. 
All analyses will be performed using SAS version 9.3 or higher (SAS Institute, Cary, North 
Carolina, USA). Continuous variables will be summarized by visit (where applicable) including 
number of subjects (n), mean, SD, median, minimum and maximum. Geometric coefficient of 
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variation (geoCV), geometric mean (geoMean) and 95% CI for the geoMean will also be 
presented in the descriptive statistics for the PK and PD concentration data. Categorical variables 
will be summarized by visit (where applicable) with frequency counts and percentages.  
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 
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 
 geoCV will be reported as a percentage to 1 decimal place 
 Minimum and maximum will be reported using the same number of decimal places as the 
original value 
 Correlations will use 3 decimal places 
 If no subjects have data at a given time point, for example, then only n=0 will be presented. 
If n<3, then only n, minimum and maximum will be presented. If n=3, then only n, mean, 
median, minimum and maximum will be presented. The other descriptive statistics will be 
left blank. 
Analyses will be performed by treatment group and for all subjects where stated. The treatment 
groups for Dosing Period 1 will be as follows and will be displayed as such in the TFLs: 
 Placebo 
 UCB7665 7mg/kg 
For Dosing Period 2 and the Observation Period the following treatment groups will be 
considered for analysis and will be displayed as such in the TFLs (the first two groups will only 
be utilized, for observation period, in case patients do not receive any dosing in period 2):  
 Placebo  
 UCB7665 7mg/kg 
 Placebo - UCB7665 7mg/kg  
 Placebo - UCB7665 4mg/kg 
 UCB7665 7mg/kg - UCB7665 7mg/kg 
 UCB7665 7mg/kg - UCB7665 4mg/kg 
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These treatment groups will be used for all safety and efficacy analyses. 
Unless stated otherwise, all statistical tests will be 1-sided and conducted at 0.05 alpha levels. 
For Dosing Period 2, only descriptive analyses will be performed. 
Data listings containing all documented data and all derived data will be generated. 
3.2 
General study level definitions 
3.2.1 
Analysis time points 
3.2.1.1 
Relative day 
Relative day for an event will be derived with the date of the first sc infusion of study drug as 
reference. 
Relative days for an event of measurement occurring before the date of first sc 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 sc 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. 
3.2.2 
Study periods 
The maximum duration of the study per subject will be approximately 18 weeks, consisting of 
the following 3 periods: 
 Screening Period: 1 to 28 days 
 Treatment Period: 6 weeks  
 Dosing Period 1 of 4 weeks. This period will start at the first actual dosing of Period 1. 
 Dosing Period 2 of 2 weeks. This period will start at the first actual dosing of Period 2. 
 Observation Period: 8 weeks 
The end of the study is defined as the date of the final clinic/hospital visit of the final subject in 
the study. 
In the case a subject does not receive dosing in Dosing Period 2, the rule for entering the 
Observation Period given in Section 2.3 will be generalized such that the subject will enter the 
Observation Period the day after the last dosing of Dosing Period 1. All data up to the missed 
dose will be treated according to plan, including data planned on the dosing day prior to the 
actual dosing. 
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The following definitions for starting and entering the study periods will be applied: 
 Started period 1 is defined as all subjects in the safety set. Completed period 1 includes those 
subjects who have completed assessments prior to the first study treatment of Period 2 (Day 
29). 
 Started period 2 is defined as having received treatment on Period 2 Day 29. Completed 
period 2 includes those subjects who have completed assessments on Observation Period Day 
50. 
 Started Observation Period is defined as having assessments on Observation Period Day 50. 
Completed observation period includes those subjects who have a completed status in the 
study termination case report form 
3.2.3 
Mapping of assessments performed at Premature End of Treatment 
Visit 
Efficacy and safety assessments at a Premature End of Treatment Visit (PEOT) that correspond 
to a scheduled visit will be summarized at the next scheduled visit. 
In particular, clinical laboratory parameters, vital signs, ECG and exploratory safety biomarkers 
are assessed at all Treatment Period visits, and so all assessments of these variables at PEOT 
corresponding to a scheduled visit will be mapped to the corresponding scheduled visit. 
3.3 
Definition of Baseline values 
Baseline will be the last available predose value prior to the first infusion of study drug in 
Dosing Period 1, or if missing, the Screening values. Scheduled or unscheduled measurements 
can be used as the Baseline value. Expected measurement-specific Baseline time points are 
presented in Table 3‒1. If an unscheduled measurement occurs after the planned baseline 
measurement time point but before dosing, then the unscheduled measurement will be used. 
Table 3‒1: 
Expected Baseline Visits 
Measurement 
Baseline 
Safety data 
 Clinical Chemistry 
 Hematology 
 Urinalysis 
 ECG 
 Vital signs 
 
 
 
 
 Body weight 
 Clinical chemistry, Hematology, 
Urinalysis, ECG and Vital signs: Predose 
Day 1 or if missing the Screening value 
 
 
 
 
: Predose Day 1 
 
 Body weight: screening visit 
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Table 3‒1: 
Expected Baseline Visits 
Measurement 
Baseline 
Pharmacodynamic data 
 Total serum IgG 
 Serum IgG subclass concentrations 
 MG specific antibodies 
(
) 
 Total serum IgG and Serum IgG subclass: 
Predose Day 1 or if missing the Screening 
value 
 
 Mg-specific autoantibodies: Predose Day 1 
Immunological data: 
 IgM, IgE, IgA 
 Serum complement levels (C3 and C4) and 
plasma complement levels (C3a and C5a) 
 
 
 Serum BAFF levels 
 Cytokines 
 
 specific IgG 
antibodies 
 Exploratory biomarkers relating to 
mechanism of action, disease activity, 
treatment response, and clinical outcome 
 IgM, IgE, IgA, C3, C4, C3a, C5a, 
 
BAFF, cytokines: Predose Day 1 
 
 
 antibodies: 
Screening 
 
 Exploratory biomarkers: Predose Day 1 
Efficacy data: 
 QMG scale 
 MG-composite scale 
 MGADL 
 MGFA scale 
 MG muscle weakness 
 Fatigue 
 MGII 
 SFEMG 
 QMG, MG composite scale and MFGA: 
Predose Day 1 or if missing the Screening 
value 
 
 MGADL, Muscle weakness, Fatigue scale, 
MGII, SFEMG: Predose Day 1. 
 BAFF=B-cell 
activating factor ; Ig=immunoglobin; MGADL=myasthenia gravis-Activities of Daily Living; MGFA=Myasthenia 
Gravis Foundation of America; MGII= Myasthenia Gravis Impairment Index; SFEMG=single fiber 
electromyography; QMG=quantitative myasthenia gravis 
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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 important protocol deviations 
will be defined within the appropriate protocol-specific document. Important protocol deviations 
will be reviewed as part of the ongoing data cleaning process and data evaluation. All important 
deviations will be identified and documented prior to unblinding to confirm 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. 
3.5.2 
Randomized Set 
The Randomized Set (RS) will consist of all subjects randomized into the study at the first 
randomization visit. 
3.5.3 
Safety Set 
The Safety Set (SS) will consist of all subjects in the RS, who have received at least 1 dose of 
IMP. 
Safety and immunological variables will be analyzed using the SS. 
It is expected that subjects will receive treatment as randomized and hence safety analyses will 
be based on the randomized treatment group. However, if after unblinding it is determined that a 
subject has received the incorrect treatment based on the randomization schedule, then for safety 
analyses the subject will be allocated to the actual treatment they received in the respective 
Dosing Period. 
3.5.4 
Full Analysis Set 
The FAS will consist of all subjects in the SS, who have a Baseline and least 1 post-Baseline 
QMG measurement during Dosing Period 1 (up to and including Visit 9, ie, Day 29). 
The FAS is the primary analysis set for efficacy analyses. As for the SS, in the case of 
mistreatment, subjects will be primarily analyzed as treated. However, if applicable, sensitivity 
analysis will also be performed according to the randomized treatment group. 
3.5.5 
Per Protocol Set 
The Per-Protocol Set (PPS) is a subset of the FAS, consisting of those subjects who had no 
important protocol deviations affecting the primary efficacy variable, as confirmed during a 
pre-analysis data review meeting conducted prior to study unblinding. Post-Baseline deviations 
will not necessarily lead to total exclusion of a subject from the PPS but may lead to exclusion of 
specific data. In the case of mistreatment the subject will be analyzed as randomized. 
Analysis of the primary efficacy variable will be repeated using the PPS. 
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3.5.6 
Pharmacokinetic Per-Protocol Set: 
The PK-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviations affecting the plasma concentration of UCB7665.  
3.5.7 
Pharmacodynamic Per-Protocol Set: 
The PD-PPS is a subset of the FAS, consisting of those subjects who had no important protocol 
deviation affecting the serum concentrations of total serum IgG or IgG subclasses. As for the SS, 
in the case of mistreatment, subjects will be primarily analyzed as treated. 
3.6 
Treatment assignment and treatment groups 
Safety, PK, PD and efficacy analyses will be assigned treatment as described in Section 3.5. 
Analyses will be performed by treatment group and for all subjects (if applicable) as described in 
Section 3.1. 
The Treatment Groups for Dosing Period 1 will be as follows: 
 Placebo 
 UCB7665 7mg/kg 
For Dosing Period 2 and the Observation Period the following treatment groups will be 
considered for analysis and will be displayed as such in the TFLs (the first two groups will only 
be utilized for observation period in case patients do not receive any dosing in period 2):  
 Placebo  
 UCB7665 7mg/kg 
 Placebo - UCB7665 7mg/kg  
 Placebo - UCB7665 4mg/kg 
 UCB7665 7mg/kg - UCB7665 7mg/kg 
 UCB7665 7mg/kg - UCB7665 4mg/kg 
These Treatment Groups will be used for all analyses. 
3.7 
Center pooling strategy 
It is planned to recruit subjects in USA, Canada, and Europe in this study, with possible 
extension to other regions and countries. The data from different sites will be pooled for all 
analyses.  
3.8 
Coding dictionaries 
All AEs and medical history will be coded for analysis according to the Medical Dictionary for 
Regulatory Activities (MedDRA)® coding dictionary, using the latest version available. Prior 
and concomitant medications will be coded for analysis using the latest version of the World 
Health Organization Drug dictionary (WHO-DD). Medical procedures will not be coded. 
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3.9 
Changes to protocol-defined analyses 
In protocol section 14.3.2, it is described that the secondary variable change from baseline in at 
Visit 9 will be analyzed utilizing similarly to the approach used for QMG. However, since 
MGADL is measured only at Visit 2 and Visit 9, it is not possible to use the repeated measures 
model and a simpler model will be used, see Section 8.2.2.  
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
In the analysis of the efficacy variables, the Baseline value of the QMG, MG-composite score, 
MGADL score or MGII score will be used as a covariate in the analysis of the respective 
variable. 
4.2 
Handling of dropouts or missing data 
In general, there will be no imputation of missing data unless stated otherwise below. 
4.2.1 
Efficacy data 
The rules for handling missing data of single items in the calculation of the overall QMG, 
MGADL or MGII scores at a certain visit are described in Section 14.1, Section 14.3 and 
Section 14.5, respectively. Missing overall scores at a certain visit will not be imputed. 
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. 
Measurements above the limit of quantification (ALQ), if applicable, will be imputed to the 
upper limit of quantification. These rules will be applied to all safety laboratory data including 
clinical chemistry and urinalysis. 
Descriptive statistics will be calculated if at most 33% of the individual data points at a time 
point are missing or are either not quantifiable (<LLOQ) or ALQ.  
4.2.3 
Pharmacodynamic data 
Measurements BLQ are not anticipated for the serum total serum IgG data. In the event that any 
measurements BLQ are received, these will be regarded as missing for the calculation of 
descriptive statistics and changes from Baseline. 
Descriptive statistics will be calculated if at most 33% of the individual data points at a time 
point are missing or are either not quantifiable (<LLOQ) or ALQ as described in Section 4.2.2. 
For the MG-specific autoantibodies and IgG subclasses, measurements BLQ will be imputed 
with LLOQ/2 for the purpose of calculating change from Baseline. Measurements ALQ, if 
applicable, will be imputed to the upper quantification limit. 
4.2.4 
Immunological data 
The rules for handling BLQ or ALQ measurements for all immunological data will be as 
described in Section 4.2.2. 
Descriptive statistics will be calculated if at most 33% of the individual data points at a time 
point are missing or are either not quantifiable (<LLOQ) or ALQ as described in Section 4.2.2. 
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4.2.5 
UCB7665 concentration data 
Measurements that are BLQ will be imputed with half of the LLOQ for the purpose of 
calculating the geoMean and its 95% CI, the geoCV, the arithmetic mean, and SD for summaries 
and figures. If any summary value (geoMean, arithmetic mean, lower CI level or minimum) is 
lower than LLOQ, then ‘BLQ’ will be displayed.  
For the individual figures, any concentrations that are BLQ will be regarded as missing, with the 
exception of predose measurements BLQ 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. 
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 time point. In the event that there are not 
3 available measurements at a given time point, the mean will be calculated based on the number 
of measurements for which data is provided.  
4.2.7 
Dates and times 
Partial dates may be imputed for the following reasons: 
 Classification of Adverse events (AEs) as treatment-emergent 
 Classification of medications as prior or concomitant 
The following rules will be applied for partial start dates/times: 
 If only start month and year are specified and not the same as  month and year of first dosing 
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 start 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 (ie, 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 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 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 (ie, event will be regarded as treatment-emergent); 
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 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 (ie, event will be regarded 
as treatment-emergent). 
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 
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 in and reported in day 
and time format: xx d hh:mm. 
Table 4‒1: 
Calculation rules for duration of AEs 
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. 
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 
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Table 4‒1: 
Calculation rules for duration of AEs 
Data 
availability 
Onset 
date/time 
Outcome 
date/time 
Calculation rules 
End day and 
time missing 
D1/T1 
--/-- 
For ongoing AE: 
Duration = >Discharge day – D1 d OR 
For resolved AE: 
Duration = <Discharge day – D1 d OR 
Where discharge refers to the date of the end of study 
visit for completed subjects 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. 
Start and end 
date missing 
--/-- 
--/-- 
For ongoing AE: 
Duration = >Discharge day – D0 d OR 
For resolved AE: 
Duration = <Discharge day – D0 d OR 
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. The following 
general rules will apply to all repeated and unscheduled measurements: 
 For repeated measurements obtained prior to the first dose of IMP 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 IMP. Repeated measurements designated Baseline will be used in 
descriptive statistics rather than the planned measurement they replace 
 For repeated measurements obtained at any time point after the first dose of IMP, 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 time points after the first dose of IMP 
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The above rules also apply to triplicate measurements obtained for the ECG data, both for 
repetitions of the whole triplicate or when single measurements of the triplicate are repeated. 
4.4 
Interim analyses and data monitoring 
At least three interim analyses will be performed. The first interim analysis for futility will be 
performed once approximately 20 subjects have attended Visit 9, the first visit of the second 
Dosing Period (ie, Day 29). Futility of UCB7665 will be assessed based on QMG score, 
MG-Composite score, and MGADL data. In case of futility, the study will be stopped or 
amended. The decision rules for futility will be described in the data monitoring committee 
(DMC) charter. The second interim analysis will be conducted after approximately 20 subjects 
(receiving 6 sc infusions) have had Visit 16 (Day 57). Based on this unblinded analysis the safety 
of UCB7665 will be assessed by the DMC. The safety variables to be used and the potential 
outcomes of the analysis will be specified in the DMC charter. During this review recruitment 
will not be stopped. The third interim analysis will be performed once all subjects have attended 
Visit 9 (Day 29), the first visit of the second Dosing Period (ie, Day 29). This interim analysis 
will provide the results for the primary variable ‘change from Baseline to Visit 9 (Day 29) in the 
QMG score’, and secondary variables ‘change from Baseline to Visit 9 (Day 29) in 
MG-Composite score’ and ‘change from Baseline to Visit 9 (Day 29) in the MGADL score’. For 
the third interim analysis the DMC will not be utilized. 
The analyses will be described in a separate Interim SAP. The first interim analysis will utilize 
all efficacy data (as specified in the DMC charter), which will be available at the time the 20th 
subject attended Visit 9. The second interim analysis will utilize all safety data (as specified in 
the DMC charter), which will be available at the time the 20th subject attended Visit 16. For all 
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 
Use of an efficacy subset of subjects 
Not applicable 
4.8 
Active-control studies intended to show equivalence 
Not applicable 
4.9 
Examination of subgroups 
Not applicable 
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/the period, as well as the reason 
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for discontinuation, discontinuation due to AEs, 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 (ES) 
 Visit dates (RS) 
 Subject analysis sets (ES) 
Subject disposition will be listed by treatment group based on the ES, and will include the date of 
informed consent, presence of informed consent for SFEMB with date, date of randomization for 
Dosing Period 1 and Dosing Period 2, date and time of first and last dose of IMP, date of 
premature termination and primary reason, and date of final contact. 
The listing of study discontinuation will include the reason for discontinuation, period of 
discontinuation, with dose and number of days on that dose and the total number of days on 
study medication. 
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 
5.2 
Protocol deviations 
Important protocol deviations (IPDs) will be identified and classified by the deviation types 
identified in the IPD document. A listing of all IPDs identified at the Data evaluation meetings 
(DEMs) 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 IPDs will be summarized 
overall if appropriate. The denominator for percentages will be the number of subjects in the SS. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
6.1 
Demographics 
A by-subject listing of Baseline demographics will be presented by treatment group for the ES. 
This will include the day, month and 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. 
Childbearing potential will be listed for the ES. 
All demographic characteristics obtained at the Screening visit will be summarized for the RS 
(apart from the date of birth). 
Body mass index 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 
The BMI will be reported to 1 decimal place. 
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The demographic characteristics listing will include a flag for BMI values identified as 
TEMA/PCS as defined by the criteria outlined in Table 14-7. 
For the EudraCT reporting, the age categories will include 
 18 to <65 years 
 65 to <85 years 
 ≥85 years 
For the clinicaltrials.gov reporting, the age categories will include: 
 ≤18 years 
 19 to <65 years 
 ≥65 years 
6.2 
Other Baseline characteristics 
MG medication (medication where indication is MG), MGFA disease class and thymectomy 
(yes/no) at baseline will be listed and summarized by treatment group for the RS. 
6.3 
Medical history and concomitant diseases 
Medical history will be listed and summarized for the RS by treatment group, and will include 
the MedDRA system organ class (SOC), high level term (HLT) and preferred term (PT). 
Procedure history and concomitant medical procedure will be listed separately from the medical 
history based on the RS. 
History of MG will be listed for the RS. 
6.4 
Past, prior and concomitant medications 
Past, prior and concomitant medications will be listed and summarized, separately, for the RS by 
treatment group and for all subjects by WHODD Anatomical Main Group [Level 1], Therapeutic 
Subgroup [Level 3], preferred term (PT) and reported term (listing only). The listing will also 
include the dose per intake and unit, frequency, formulation, route of administration, indication, 
category (three categories; prior, concomitant and prior and concomitant), study period (Dosing 
Period 1, Dosing Period 2 and/or Observation Period) and both start and end date (or ongoing, if 
applicable).  
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). 
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6.4.1 
Past medication definition 
Past medications will include any medications that started and stopped prior to the first IMP 
administration. 
6.4.2 
Prior medication definition 
Prior medications will include any medications that started prior to the first administration of 
IMP. This includes any medications that started and stopped prior to dosing (past medications) as 
well as those which started prior to dosing and continued after (classified as prior and 
concomitant medications). 
6.4.3 
Concomitant medication definition 
Concomitant medications will include any medication that has been taken at least once (after the 
first administration of IMP) during the Dosing Periods and/or the Observation Period.  
Any medication that started prior to the first administration of IMP and continued after dosing 
will be classified as prior and concomitant. Any medication that started after the first 
administration of IMP in Dosing Period 1 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 or concomitant. 
6.4.4 
Assignment of medications to study period 
The following rules will be used to assign a concomitant medication to a study period: 
 Dosing Period 1: a medication will be assigned to Dosing Period 1 if it has been taken at least 
once between the first administration of IMP on Day 1 and the first administration of IMP in 
Dosing Period 2 (Day 29). This includes medications that started prior to Dosing Period 1 
and those that continued into Dosing Period 2. 
 Dosing Period 2: a medication will be assigned to Dosing Period 2 if it has been taken at least 
once between the first administration of IMP in Dosing Period 2 (Day 29 and 7 days after the 
last dose of IMP in Dosing Period 2 [Day 50]). This includes medications that started prior to 
Dosing Period 2 and those that continued into the Observation Period. 
 Observation Period: a medication will be assigned to the Observation Period if it has been 
taken at least once between Day 50 (or 7 days after the last dose of IMP) and the final visit. 
This includes medications that started prior to the Observation Period. 
Thus, a medication taken from the time of the first drug administration in Dosing Period 1 to the 
end of the study will be assigned to Dosing Period 1, Dosing Period 2 and the Observation 
Period. 
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 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. 
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There will be no specific analysis of compliance. Exposure to UCB7665 will be presented as 
described in Section 11.1. 
8 
EFFICACY ANALYSES 
8.1 
Statistical analysis of the primary efficacy variable 
The primary efficacy variable is the change from Baseline in QMG score to Visit 9 (Day 29) 
prior to the first infusion of IMP in Dosing Period 2. 
8.1.1 
Derivations of primary efficacy variable 
The QMG scale comprises 13 items, including ocular and facial movement, swallowing, speech, 
limb strength and forced vital capacity. Scoring for each item ranges from no weakness (0) to 
severe weakness (3), with an overall score range from 0 to 39, ie, a higher scores indicates more 
severe disease. A 3-point change in the overall score is considered to be clinically relevant. 
The complete list of items and scores are provided in Table 14‒1. The items of QMG scale will 
be displayed in a glossary. A total score after single item imputation will be calculated according 
to the rules set down in Section 14.1. All individual item results will be listed. The total score 
after single item imputation will be listed and used to calculate change from baseline, in 
descriptive summaries and for efficacy analysis. Total score will be used to determine responder 
state, which will be flagged in the listing and descriptively summarized.  
8.1.2 
Primary analysis of the primary efficacy variable 
A 1-sided hypothesis test will be performed to test the primary hypothesis of superiority of 
UCB7665 7mg/kg vs placebo at Visit 9. The null hypothesis is that the mean change from 
Baseline in QMG score is larger or equal in the UCB7665 7mg/kg group than the placebo group. 
The alternative hypothesis is that the mean change from Baseline in QMG score is smaller in the 
UCB7665 7mg/kg group than the placebo group.  
The primary analysis of the primary variable will be analyzed for the FAS using a mixed model 
repeated measures (MMRM) analysis of covariance (ANCOVA) that includes terms for week (as 
categorical effect), treatment group, the Baseline QMG score, and the interaction between 
treatment group and week. The model will define subject as a random effect and utilize an 
unstructured covariance pattern. Least Squares (LS) Means for changes from Baseline at Visit 9 
(Day 29) for each treatment group will be presented together with LS mean differences 
(UCB7665 - 7mg/kg vs placebo), p-value and 1 sided 95% CI.  
For subjects who prematurely withdraw for any reason before Visit 9 (Day 29), data collected 
during the PEOT Visit will be used to impute QMG scores at the next consecutive visit. 
8.1.3 
Supportive and sensitivity analyses of the primary efficacy variable 
Different sensitivity analyses to evaluate the effect of missing observations on the primary 
analysis findings will be done. The first sensitivity analysis will be performed in the same way as 
the primary analysis but will use PPS instead. A further analysis will utilize the Last Observation 
Carried Forward (LOCF) approach and the FAS; missing values will be replaced by the last 
observed post-Baseline value of the variable and the analysis will be performed on the resulting 
dataset. 
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8.2 
Statistical analysis of the secondary efficacy variables 
The secondary efficacy variables are the changes from Baseline in MG-Composite and MGADL 
scores to Visit 9 (Day 29) prior to the first infusion of IMP in Dosing Period 2. 
The MG-composite score comprises 10 items, each of which is weighted differently in the 
calculation of the overall score. The overall score ranges from 0 to 50, with a higher score 
indicating more severe disease. The items of MG-composite score will be displayed in a 
glossary. All individual item results will be listed. The total score will be listed and used to 
calculate change from baseline and used in descriptive summaries and for efficacy analysis. 
Total score will be used to determine responder state, which will be flagged in the listing and 
descriptively summarized.  
The complete list of items and scores are provided in Table 14‒2 .  
The MGADL score comprises of 8 items, each with a score of 0 to 3. The items of MGADL will 
be displayed in a glossary. The total MGADL score ranges from 0 to 24 with a higher score 
indicating more disability. The complete list of items and scores are provided in Table 14‒3. The 
total score will be calculated according to the rules set down in Section 14.3 All individual item 
results will be listed. The MGADL listing will contain total score for an interpolated visit at Day 
57, where the total score is derived based on interpolation of Day 50 and 64. If total score on 
either day 50 or day 64 is not available no interpolated score will be derived. The total score after 
single item imputation will be listed and used to calculate change from baseline and used in 
descriptive summaries and for efficacy analysis, interpolated data from Day 57 will be part of the 
descriptive summary. Total score will be used to determine responder state, which will be 
flagged in the listing and descriptively summarized.  
A comparison summary of MGADL showing absolute scores of Visit 9 (day 29), interpolated 
Day 57 and their differences will be presented by treatment group of second treatment period 
(Placebo - UCB7665 7mg/kg, Placebo - UCB7665 4mg/kg, UCB7665 7mg/kg - UCB7665 
7mg/kg, UCB7665 7mg/kg - UCB7665 4mg/kg). 
8.2.1 
MG-composite score 
The MG-composite score will be analyzed utilizing the MMRM ANCOVA. A 1-sided 
hypothesis test will be performed to test the hypothesis of superiority of UCB7665 7mg/kg vs 
placebo at Visit 9. The null hypothesis is that the mean change from Baseline in MG-composite 
score is larger or equal in the UCB7665 7mg/kg group than the placebo group. The alternative 
hypothesis is that the mean change from Baseline in MG-composite score is smaller in the 
UCB7665 7mg/kg group than the placebo group.  
The change from baseline of the MG-composite score will be analyzed for the FAS using a 
MMRM ANCOVA that includes terms for week (as categorical effect), treatment group, the 
Baseline MG-composite score, and the interaction between treatment group and week. The 
model will define subject as a random effect and utilize an unstructured covariance pattern. Least 
Squares (LS) Means for changes from Baseline at Visit 9 (Day 29) for each treatment group will 
be presented together with LS mean differences (UCB7665 - 7mg/kg vs placebo), p-value and 1 
sided 95% CI.  
For subjects who prematurely withdraw for any reason before Visit 9 (Day 29), data collected 
during the PEOT Visit will be used to impute MG-composite scores at the next consecutive 
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visit.. There will be no sensitivity analysis for the MG-composite score. Subjects without 
baseline value will not be analyzed. 
8.2.2 
MG activities of daily living 
Since the MGADL does not have repeated observations per subject, the MGADL score will be 
analyzed via a simplified version of the model. The change from baseline MGADL will be 
analyzed for the FAS using a ANCOVA that includes terms for treatment group and the Baseline 
score. Least Squares (LS) Means for changes from Baseline at Visit 9 for each treatment group 
will be presented together with LS mean differences (UCB7665 - 7mg/kg vs placebo), p-value 
and 1 sided 95% CI. Subjects without baseline or Visit 9 observations will not be analyzed. 
There will be no sensitivity analysis for MGADL. 
8.3 
Analysis of other efficacy variables 
8.3.1 
Summaries of efficacy variables 
Values and change from Baseline in QMG, MG-Composite and MGADL at each scheduled visit 
will be descriptively summarized at each scheduled assessment during Treatment and 
Observation Periods. MGFA classification will be summarized during Treatment and 
Observation Periods. 
8.3.2 
Muscle weakness severity and fatigability scale 
The Muscle weakness severity and fatigability scale is displayed in Section 14.4. It consists of a 
domain for muscle weakness on a total scale from 0 to 90 and a domain for fatigability on a total 
scale from 0 to 36. The total scale ranges from 0 to 126 with a higher score indicating more 
disability. The items of the muscle weakness and fatigability scale will be displayed in a 
glossary. All individual item results will be listed per time point, including total per domain and 
total. The total score will be used to calculate change from baseline and used in descriptive 
summaries and for efficacy analysis. Total score will be descriptively summarized by treatment 
and time point. 
Muscle weakness severity and fatigability scale at each assessed post-Randomization Visit 
(during Dosing Period 1 including Visit 9) will also be analyzed utilizing the MMRM approach. 
A 1-sided hypothesis test will be performed to test the hypothesis of superiority of UCB7665 
7mg/kg vs placebo at Visit 9. The null hypothesis is that the mean change from Baseline in 
muscle weakness score is larger or equal in the UCB7665 7mg/kg group than the placebo group. 
The alternative hypothesis is that the mean change from Baseline in muscle weakness score is 
smaller in the UCB7665 7mg/kg group than the placebo group.  
The change from baseline of the muscle weakness score will be analyzed for the FAS using a 
MMRM ANCOVA that includes terms for week (as categorical effect), treatment group, the 
Baseline muscle weakness score, and the interaction between treatment group and week. The 
model will define subject as a random effect and utilize an unstructured covariance pattern. Least 
Squares (LS) Means for changes from Baseline at Visit 9 (Day 29) for each treatment group will 
be presented together with LS mean differences (UCB7665 - 7mg/kg vs placebo), p-value and 1 
sided 95% CI.  
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For subjects who prematurely withdraw for any reason before Visit 9 (Day 29), data collected 
during the PEOT Visit will be used to impute muscle weakness scores at the next consecutive 
visit.  
The complete lists of items and scores are provided in Table 14‒4 and Table 14‒5. 
8.3.3 
Fatigue Instrument 
The fatigue instrument consists of 55 items across 3 domains: 16 physical domain items (with a 
scale of 16 to 80), 18 mental domain items (with a scale of 18 to 90), and 21 fatigability domain 
items (with a scale of 21 to 105). The subject will be asked to score each item based on how 
frequently she/he experienced the item during the past 7 days using a 5-point Likert scale (“none 
of the time” to “all of the time”). The items of the fatigue instrument will be displayed in a 
glossary. The overall score ranges from 55 to 275, with a higher result indicating more severe 
fatigue. All individual item results will be listed per time point including overall score. Change 
from baseline will be calculated for the overall score and both overall score and change from 
baseline will be used in descriptive summaries and for efficacy analysis. Overall score will be 
descriptively summarized by treatment and time point. 
Fatigue scale at each assessed post-Randomization Visit (during Dosing Period 1 including Visit 
9) will also be analyzed utilizing the MMRM approach. A 1-sided hypothesis test will be 
performed to test the hypothesis of superiority of UCB7665 7mg/kg vs placebo at Visit 9. The 
null hypothesis is that the mean change from Baseline in fatigue instrument score is larger or 
equal in the UCB7665 7mg/kg group than the placebo group. The alternative hypothesis is that 
the mean change from Baseline in fatigue instrument score is smaller in the UCB7665 7mg/kg 
group than the placebo group.  
The change from baseline of the fatigue instrument score will be analyzed for the FAS using a 
MMRM ANCOVA that includes terms for week (as categorical effect), treatment group, the 
Baseline muscle weakness score, and the interaction between treatment group and week. The 
model will define subject as a random effect and utilize an unstructured covariance pattern. Least 
Squares (LS) Means for changes from Baseline at Visit 9 (Day 29) for each treatment group will 
be presented together with LS mean differences (UCB7665 - 7mg/kg vs placebo), p-value and 1 
sided 95% CI.  
For subjects who prematurely withdraw for any reason before Visit 9 (Day 29), data collected 
during the PEOT Visit will be used to impute fatigue instrument scores at the next consecutive 
visit. 
8.3.4 
MGFA Clinical Classification 
The MGFA Clinical Classification is a 5 stage classification (I to V), with a higher class 
indicating more severe disease. Results of MGFA Clinical Classification will be listed. 
The percentage of subjects with each MGFA classification at each scheduled assessment during 
Treatment and Observation Periods will be calculated and descriptively summarized for the FAS. 
8.3.5 
MG Impairment Index 
The MGII consists of a 22 items patient questionnaire and an 8 item examination. It is divided in 
two sub-scores reflecting an ocular and a generalized domain. The ocular score is calculated by 
summing 8 items reflecting ocular impairments. These items are: patient questionnaire items 1 to 
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6 and examination items 1 and 2. The generalized score is calculated by adding items 7 to 22 
from the patient questionnaire and items 3 to 6 from the examination. The complete list of items 
is given in Table 14‒6. The items of MGII will be displayed in a glossary. All individual item 
results will be listed per time point including overall score. Change from baseline will be 
calculated for the overall score and sub-scores (ocular and generalized domain). The overall 
score, two sub-scores and their change from baseline will be used in descriptive summaries and 
for efficacy analysis. For overall score and sub-scores, missing items will be imputed according 
to the rules set in Section 14.5. Descriptive summaries will be by treatment and time point. 
The change from baseline MGII scale at each assessed post-Randomization Visit (during Dosing 
Period 1 including Visit 9) will also be analyzed utilizing the MMRM approach. A 1-sided 
hypothesis test will be performed to test the hypothesis of superiority of UCB7665 7mg/kg vs 
placebo at Visit 9. The null hypothesis is that the mean change from Baseline in MGII score is 
larger or equal in the UCB7665 7mg/kg group than the placebo group. The alternative hypothesis 
is that the mean change from Baseline in MGII score is smaller in the UCB7665 7mg/kg group 
than the placebo group.  
The change from baseline of the MGII score will be analyzed for the FAS using a MMRM 
ANCOVA that includes terms for week (as categorical effect), treatment group, the Baseline 
muscle weakness score, and the interaction between treatment group and week. The model will 
define subject as a random effect and utilize an unstructured covariance pattern. Least Squares 
(LS) Means for changes from Baseline at Visit 9 (Day 29) for each treatment group will be 
presented together with LS mean differences (UCB7665 - 7mg/kg vs placebo), p-value and 1 
sided 95% CI.  
For subjects who prematurely withdraw for any reason before Visit 9 (Day 29), data collected 
during the PEOT Visit will be used to impute MGII scores at the next consecutive visit.  
8.3.6 
Responder rates 
QMG, MG-Composite, and MGADL responder rates will be summarized at each assessed post-
Randomization Visit (during Dosing Period 1) and compared between the 2 Treatment Groups 
utilizing Fisher’s exact test for each visit for the FAS.  
The frequency of attained point improvement will be plotted against treatment for Visit 9 (Week 
8). For each point improvement the test result will be displayed in a table and in the plot. 
8.3.7 
Single Fiber Electromyogram 
Jitter (SFEMG) results will be listed, including change from Baseline.  
Three variables will be further analyzed; MCD of the IPI accepted after external review, % 
Normals accepted after external review and % Blocking accepted after external review. For these 
variables the listing will include change from baseline. In addition, for these variables observed 
values and change from baseline will be summarized using descriptive statistics, by treatment 
group and visit, including changes from Baseline for the FAS. 
Change from baseline line MCD accepted after external review will be plotted against change 
from baseline in efficacy variables, QMB, MG-composite and MGADL. 
Clinically meaningful improvement in jitter (SFEMG) will be calculated upon MCD of the IPI 
accepted after external review. Clinically meaningful improvement, defined as a reduction in 
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MCD of at least 9us, will be flagged in the listing. Contingency tables will be created of jitter 
(SFEMG) clinically meaningful improvement against QMG, MG-composite and MGADL 
responders by treatment. 
8.3.8 
Correlation analysis 
Pearson correlation of patient reported outcomes (PROs) with IgG levels and association using 
Spearman’s correlation with 
, 
and 
 status will be displayed by visit. 
In addition Pearson correlation of the clinical assessment of disease activity (variables QMG and 
MG composite), disease severity (MGFA) and patients’ assessment on impact on daily life 
(MG-ADL) will be displayed for each visit. This analysis will be repeated using baseline 
corrected values of the PROs and the variables QMG, MG composite, MGFA and MG-ADL. 
Further association between PROs will also be investigated using Pearson correlation.  
8.3.9 
Psychometric analyses 
The Psychometric analyses of the newly developed measures MG muscle weakness severity and 
fatigability and fatigue scales will be performed blinded from treatment arms. This psychometric 
analysis of the MG muscle weakness severity and fatigability scale and fatigue scale will be 
performed by a vendor using Rasch analysis and will be reported separately from the CSR. For 
these analyses a separate psychometric analysis plan will be written. Subsequently, the data will 
be further analysed using Rasch models, with the aim to decrease the number of items and 
develop a scoring algorithm, this is not described in this SAP and will not reported in the CSR. 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS  
9.1 
Pharmacokinetics 
The PK variable is the plasma concentration of UCB7665. Pharmacokinetic parameters such as 
Cmax and area under the curve will not be derived (eg, by non-compartmental analysis) due to 
the limited sampling performed at each visit. 
Individual concentrations of UCB7665 will be listed for the SS and summarized for the PK-PPS 
at each scheduled time point. In the listing relative and absolute time will be displayed. Relative 
time of pre-dose samples will be relative to start of infusion and display pre-dose for samples 
prior to dosing and display actual relative time for samples not prior to dosing. Relative time of 
post-dose samples will be relative to end of infusion. Descriptive statistics of concentrations will 
be calculated only if at least two thirds of the individual data points are quantifiable (≥LLOQ). 
Summaries will include 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 LLOQ will be reported with a clear sign indicating that they 
were below the LLOQ. Individual concentrations of UCB7665 will also be displayed graphically 
on a linear and on a semi-log scale. UCB7665 concentrations also be displayed in a spaghetti 
plot by treatment group on a linear and on a semi-log scale. In the spaghetti plot, time will 
9.2 
Pharmacodynamics 
The analysis of the PD data will be performed on the FAS with the exception of the total serum 
IgG and IgG subclasses results, which will be analyzed on the PD-PPS. All listings will be 
presented for the SS.  
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Any values that are BLQ or ALQ will be handled as described in Section 4.2.2. 
All analyses described in this section will be performed on the PD-PPS. 
9.2.1 
Total serum IgG and IgG subclasses 
Total serum IgG concentrations and IgG subclasses will be listed by treatment and time point 
including changes from Baseline and percentage changes from Baseline. Descriptive summaries 
(including n, arithmetic mean, median, SD, minimum and maximum) will be presented by 
treatment group and time point for absolute values, changes from Baseline and percentage 
changes from Baseline. The maximum decrease from Baseline in total serum IgG (absolute and 
percentage decrease) will be reported in the listing and summarized for each treatment.  
In the event that a decrease from Baseline in total serum IgG is not observed in a given subject, 
the maximum decrease will be reported as the smallest increase from Baseline. Mean and mean 
percentage change from Baseline values in total serum IgG will be plotted over time by 
treatment and period with all treatments overlaid on the same plot.  
9.2.2 
MG-specific autoantibodies 
MG-specific autoantibodies 
 will be listed by treatment and time point 
including changes from Baseline and percentage changes from Baseline. Descriptive summaries 
(including n, arithmetic mean, median, SD, minimum and maximum) will be presented by 
treatment group and time point for absolute values, changes from Baseline and percentage 
changes from Baseline.  
Mean and mean percentage change from Baseline values in MG-Specific autoantibodies will be 
plotted over time by treatment and period with all treatments overlaid on the same plot.  
10 
IMMUNOLOGICAL ANALYSES  
All analyses described in this section will be based on the SS. 
10.1 
Immunoglobulins 
Immunoglobulins (IgE, IgA and IgM) will be listed by treatment group and time point including 
changes from Baseline. Descriptive summaries will be presented by treatment group and time 
point for both absolute values and changes from Baseline. 
Individual figures over time (absolute value) will be presented by subject, with all variables 
overlaid on the same plot and separate plots each subject. 
Any values that are BLQ or ALQ will be handled as described in Section 4.2.4. 
10.2 
 
Immunological variables will be analyzed for all subjects in the SS. 
 
data will be summarized at each scheduled visit, and the rate of 
 positive subjects will be 
calculated. 
Dependent on availability the intention is to use a 
 screening assay without a calibrator. A 
cut point will be determined by the bioanalytical laboratory that will be used to determine the 
status of 
 as above the cut point (ACP) or below the cut point (BCP). A calibrator screening 
assay currently in place to measure 
 as relative mass units (RMU) in units/mL will be used 
in the event that the newer screening assay is unavailable.  
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A cut point will be determined by the bioanalytical laboratory that will be used to determine the 
status of 
 as above the cut point (ACP) or below the cut point (BCP). For any 
 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). In the case of 
the newer screening assay; for samples that are CP a further titre assay will be performed and the 
 titre reported.  In lieu of the newer screening assay, the RMU result from the calibrator 
screening assay will be used to report 
 levels.  
The results for the 
 measurements will be listed by treatment group and time point based on 
the SS, including the screening assay, confirmatory assay and either the titre or level in units/mL 
(as applicable).  
The following definitions will be applied: 
 An 
 status of positive will be concluded for any subject with an 
 level that is ACP 
and CP at any time point  
 An 
 status of negative will be concluded for any subject with an 
 level that is either 
BCP or ACP and NCP at any time point 
 A subject will be classified as having 
 positivity at Baseline if the Day 1, predose result 
is ACP and CP 
 A subject will be classified as having treatment-induced 
 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 titre or units/mL (as applicable) 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 
 status is 
negative (this includes subjects who have positive [ACP and CP] results at Baseline) 
The 
 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-induced 
 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-induced 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. 
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A separate listing will be presented (based on the SS) showing the UCB7665 concentrations and 
 measurements in the same output in adjacent columns. The listing will include the 
UCB7665 concentration, 
 status (ACP or BCP) and confirmatory assay results if applicable 
(NCP or CP), together with the titre or units/mL (as applicable) 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 
 titre or 
units/mL (as applicable) 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 
 titre data will be plotted using a semi-logarithmic scale. 
The rules for handling values that are BLQ in the UCB7665 concentration data are described in 
Section 4.2.5 For the 
 data, any negative results for which there are no titres or units/mL (as 
applicable) available at a specific visit will be substituted with 0.001 for the purpose of the 
figure. 
10.3 
Serum complement levels and plasma complement levels 
Serum (C3 and C4) and plasma (C3a and C5a) complement variables will be listed by treatment 
group and time point including changes from Baseline. Descriptive summaries (including n, 
arithmetic mean, median, SD, minimum and maximum) will be presented by treatment group 
and time point for both absolute values and changes from Baseline. 
Any values are that BLQ or ALQ will be handled as described in Section 4.2.4. 
10.4 
Serum BAFF levels 
Serum BAFF levels will be listed by treatment group and time point including changes from 
Baseline. Descriptive summaries (including n, arithmetic mean, median, SD, minimum and 
maximum) will be presented by treatment group and time point for both absolute values and 
changes from Baseline. 
Any values are that BLQ or ALQ will be handled as described in Section 4.2.4. 
10.5 
Cytokines 
Cytokines will be listed by treatment group and time point, changes from Baseline will be added 
to the listing. Descriptive summaries (including n, arithmetic mean, median, SD, minimum and 
maximum) will be presented by treatment group and time point for both absolute values and 
changes from Baseline, both for all subjects and for subjects experiencing infusion reactions. 
Any values are that BLQ or ALQ will be handled as described in Section 4.2.4.    
10.6 
 
 will be listed by treatment group and time 
point. I subjects experiencing infusion reactions changes from Baseline will be added to the 
listing. For subjects experiencing infusion reactions, descriptive summaries (including n, 
arithmetic mean, median, SD, minimum and maximum) will be presented by treatment group 
and time point for both absolute values and changes from Baseline. 
Any values are that BLQ or ALQ will be handled as described in Section 4.2.4.    
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11 
SAFETY ANALYSES 
All safety analyses will be presented using the SS. Listings will be presented by Dosing Period, 
treatment group and subject; tabulations will be presented by Dosing Period and treatment group 
in the following order: 
Dosing Period 1: 
 Placebo 
 UCB7665 7mg/kg 
For Dosing Period 2 and the Observation Period the following treatment groups will be 
considered for analysis and will be displayed as such in the TFLs (the first two groups will only 
be utilized for observation period in case patients do not receive any dosing in period 2):  
 Placebo  
 UCB7665 7mg/kg 
 Placebo - UCB7665 7mg/kg  
 Placebo - UCB7665 4mg/kg 
 UCB7665 7mg/kg - UCB7665 7mg/kg 
 UCB7665 7mg/kg - UCB7665 4mg/kg 
11.1 
Extent of exposure 
All drug administration details (including date, start and stop time of infusion, location of 
infusion site, interruptions, discontinuations, body weight, dose, volume delivered, percent of 
planned dose) will be listed using the SS. The reasons for any interruptions or discontinuations 
will be included in the listing. 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 (%) = (Actual volume/Planned volume)*100 
For all subjects the planned volume is 10mL. 
In Dosing Period 1 subjects will be randomized (1:1) to receive one of the following treatments: 
 3 sc doses of UCB7665 7mg/kg at 1 week intervals 
 3 sc doses of placebo at 1 week intervals 
In Dosing Period 2 subjects will be rerandomized (1:1) to receive one of the following 
treatments: 
 3 sc doses of UCB7665 7mg/kg at 1 week intervals 
 3 sc doses of UCB7665 4mg/kg at 1 week intervals 
The randomization in Dosing Period 2 will be stratified by the treatment received in Dosing 
Period 1. 
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11.2 
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 categorized by relationship to UCB7665. 
In addition, AEs will be classified according to the Common Terminology Criteria for Adverse 
Events (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).  
A TEAE is defined as any event that was not present prior the first administration of IMP or any 
unresolved event already present before the first administration of IMP that worsens in intensity 
following exposure to treatment. Adverse events starting before the first administration of IMP 
or after 8 weeks following the final dose of IMP will not be considered TEAEs. Thus AEs before 
first dosing and AEs after 8 weeks following the final dose will be combined in one category. 
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. 
The following rules will be used to assign a TEAE to a study period: 
 Dosing Period 1: a TEAE will be assigned to Dosing Period 1 for the tabulations if the start 
date/time of the event is at the time of or after the first administration of IMP on Day 1, up to 
the time of actual first administration of IMP in Dosing Period 2 (planned for Day 29) 
 Dosing Period 2 or Observation Period: a TEAE will be assigned to ‘Dosing Period 2 or 
Observation Period’ for the tabulations if the start date/time of the event is at the time of or 
after the first administration of IMP (planned for Day 29), until 8 weeks following the final 
dose; events starting later than 8 weeks following the final dose of IMP are not considered 
TEAEs 
In the case of early withdrawal in either Dosing Period 1 or 2, a TEAE will be assigned to the 
respective Dosing Period based on the last received infusion. 
The number and percentage of subjects who experience TEAEs will be summarized for each 
Dosing Period and treatment group. In all tabulations, TEAEs occurring during the Observation 
Period will be presented as part of Dosing Period 2. In addition summaries for total active and all 
treatments will be created. 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, 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 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 
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 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 
Summary tables will contain counts of subjects, percentages of subjects in parentheses and the 
number of events. 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 the TEAEs above threshold of 5% only those AEs will be included which are present at 5% of 
the subjects within a treatment group.  
Adverse event summaries will be ordered by alphabetical SOC, alphabetical HLT within SOC 
and decreasing frequency of PT in the ‘Period 2 UCB7665 7mg/kg - UCB7665 7mg/kg’ column 
for tables.  
A listing will be presented by treatment group and subject for all AEs. This will include the onset 
date/time and outcome date/time of the event (including relative days), the AE duration, days 
since first dose of IMP, days since most recent dose of IMP, pattern of event, severity/intensity, 
relationship, action taken and outcome. In addition the listing will flag AEs that led to 
discontinuation, TEAEs, serious adverse events (SAEs), AEs of interest, AEs of special interest 
and infusion reactions. 
AEs of interest are: 
 Severe headache 
 Moderate to severe diarrhea 
 Moderate to severe abdominal pain 
 Moderate to severe vomiting 
AEs of special interest are Potential Hy’s Law, defined as ≥3x upper limit of normal (ULN) 
Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) with coexisting ≥2xULN 
total bilirubin in the absence of ≥2xULN alkaline phosphatase (ALP), with no alternative 
explanation for the biochemical abnormality. 
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11.3 
Clinical laboratory evaluations 
Laboratory data (chemistry, hematology and urinalysis) and changes from Baseline (if 
applicable) for numeric variables will be summarized by treatment group and time point. 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. The 
reference ranges will also be reported in the listings. In addition, the listings will include a flag 
for values identified as treatment-emergent markedly abnormal (TEMA)/potentially clinically 
significant (PCS) as defined by the criteria outlined in Table 14-7. 
Chemistry, hematology and coagulation parameters will be summarized by treatment group at 
each time point, for both absolute values and changes from Baseline.  
The laboratory variables are presented in Table 11‒1. For selected laboratory variables that are 
identified in Table 11‒1, the change in category from Baseline will be presented in shift tables at 
each post-Baseline assessment. 
Table 11‒1: Clinical laboratory measurements 
Category 
Panel 
Variable 
Hematology 
Red blood cell 
RBC count, hemoglobin, 
hematocrit, HbA1c 
 
Platelet 
Platelet count
a 
 
White blood cell 
WBC count 
 
White blood cell differential 
Absolute counts: ANC, 
basophils, eosinophils, ALC, 
monocytes 
Percentages: 
neutrophils/leukocytes, 
basophils/leukocytes, 
eosinophils/leukocytes, 
lymphocytes/leukocytes, 
monocytes/leukocytes 
Chemistry 
Electrolytes 
Sodium, chloride, potassium, 
calcium, phosphate, magnesium 
 
Enzymes 
Amylase, Creatine kinase 
 
Hormones 
procalcitonin 
 
Kidney function 
Urea-N, creatininea 
 
Proteins 
Total protein, albumina, alpha- 
and beta- globulins, hsCRPa 
 
Liver function 
ASTa, ALTa, GGT, ALP, LDH, 
total bilirubin, direct bilirubin (if 
indicated) 
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Table 11‒1: Clinical laboratory measurements 
Category 
Panel 
Variable 
 
Lipids 
Total cholesterol, LDL 
cholesterol, HDL cholesterol, 
triglycerides 
Urinalysis 
Dipstick 
pH, protein, glucose, ketones, 
urobilinogen, bilirubin, blood, 
nitrite, leucocytes 
 
Quantitative 
Albumin, creatinine, protein 
 
Sediment 
Leukocytes 
a Shift table will be created for these variables 
ALC=absolute lymphocyte count; ALP=alkaline phosphatase; ALT=alanine aminotransferase; ANC=absolute 
neutrophil count; aPTT=activated partial thromboplastin time; AST=aspartate aminotransferase; BUN=blood urea 
nitrogen; GGT=gamma-glutamyltransferase; HbA1c=glycosylated hemoglobin; HBsAG=hepatitis B surface 
Antigen; HCV Ab=hepatitis C virus antibody; HDL=high density lipoprotein; hsCRP=high sensitivity C-reactive 
protein; LDH=lactate dehydrogenase; LDL=low density lipoprotein; RBC=red blood cell; WBC=white blood cell. 
11.3.1 
Potential drug-induced liver injury 
A separate listing will present subjects who meet one or more of the following potential drug-
induced liver injury (PDILI) criteria at any visit: 
 Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥5x Upper limit of 
normal (ULN)   
 ALT or AST increase ≥3x ULN and Total bilirubin ≥2x ULN 
 ALT or AST ≥3x ULN who exhibit temporally associated symptoms of hepatitis or 
hypersensitivity 
 ALT or AST ≥3xULN (and ≥2x Baseline) and <5xULN, total bilirubin <2xULN, and no 
eosinophilia (i.e., ≤5%), with no fever, rash, or symptoms of hepatitis. 
The listing will display only visits for which at least one of the above criteria was fulfilled for a 
given subject, and will display all results obtained at that visit for the specified parameters. 
A summary of subjects who met the criteria for PDILI will be presented together with any 
additional relevant data collected, if applicable. 
11.4 
Vital signs, physical findings, and other observations related to 
safety 
11.4.1 
Vital signs 
The following vital signs measurements will be obtained: 
 Pulse rate 
 Systolic and diastolic blood pressure 
 Temperature (oral preferred, ear or axillary permitted) 
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 Respiratory rate 
A by-subject listing of all vital sign measurements and change from Baseline will be presented 
by treatment group and time point. The listing will include a flag for values identified as 
TEMA/PCS as defined by the criteria outlined in Table 14-7. 
Descriptive statistics will be reported for all vital sign measurements. Measured values and 
changes from Baseline will be summarized by vital signs variables and time point for each 
treatment group. Summarization will be as treated, subjects who missed treatments will not be 
summarized. 
Repeated and unscheduled measurements will be handled as described in Section 4.3. 
11.4.2 
Electrocardiograms  
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 for assessments of 
laboratory variables. The following variables will be reported: 
 Heart rate 
 RR interval 
 PQ/PR interval 
 QRS duration 
 QT interval 
 QT corrected for heart rate using Bazett’s formula (QTcB = QT/RR1/2) 
 QT corrected for heart rate using Fridericia’s formula (QTcF = QT/RR1/3) 
The individual measurements and the mean of the triplicate measurements will be reported in the 
by-subject listings. The listing will include the change from Baseline (based on the mean of the 
triplicate measurements at each time point) and will be presented by treatment group and time 
point. The listing will also include a flag for values identified as TEMA/PCS TEMA/PCS as 
defined by the criteria outlined in Table 14-7. 
Measured values and changes from Baseline will be summarized by treatment group at each time 
point and by ECG variable (based on the mean of the triplicate values at each time point). 
Summarization will be as treated, subjects who missed treatments will not be summarized. 
Electrocardiogram findings for the individual triplicate measurements will be listed separately. 
Frequency counts of normal vs abnormal findings will be presented by treatment group and time 
point. 
Repeated and unscheduled measurements will be handled as described in Section 4.3. 
In the event that the complete set of triplicate measurements is not available at a specified time 
point the data will be handled as described in Section 4.2.6. 
11.4.3 
Exploratory safety biomarkers 
Serum biomarkers (
, 
 only in subjects with severe headache and/or moderate to severe GI 
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disturbance) will be listed by treatment group and time point including changes from Baseline. 
Descriptive summaries (including n, arithmetic mean, median, SD, minimum and maximum) 
will be presented by treatment group and time point for both absolute values and changes from 
Baseline. 
Mean and mean change from Baseline values will be plotted over time by treatment group with 
all treatment groups overlaid on the same plot and separate plots for each variable. 
Any values that are BLQ or ALQ will be handled as described in Section 4.2.2.  
11.4.4 
Physical examination 
Results of physical examination will be listed. 
11.4.5 
Other safety variable 
Results of interferon-gamma release assay (IGRA) tuberculosis test will be listed. 
Results of Serum pregnancy test will be listed. 
Results of tuberculosis signs and symptoms questionnaire will be listed. 
Results of serology testing for human immunodeficiency virus (HIV), Hepatitis B and Hepatitis 
C will be listed. 
Suicidal ideation will be queried according to the scheduled in table 5.1 of the CSP. A full 
Columbia Suicide Severity Rating Scale (C-SSRS) assessment will be performed only when 
subject has a positive response to the suicidal ideation query. Results of suicidal ideation and 
C-SSRS will be listed. 
Full Neurological examination will be performed at screening and at Visit 9 (Day 29). Brief 
neurological examination will be performed at Visit 2 (Baseline) and Visit 9 (day 29). Results of 
the neurological examinations will be listed. 
12 
OTHER ANALYSES  
Vaccination-specific antibody titres (
 will be listed. 
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 (if indicated) at the 
discretion of the investigator and may include, eg, a computed tomography (CT) scan, magnetic 
resonance imaging (MRI) and/or a lumbar puncture (LP) for cerebral spinal fluid(CSF) 
collection. In addition assessment of exploratory safety biomarkers should be performed for 
subjects experiencing severe headache. These investigations will be performed in order to further 
understand the mechanism of headache in these subjects. 
The results of the headache questionnaire, neurological examination and any additional tests 
performed (CT scan, fundoscopy and LP for CSF collection) will be listed for each subject. No 
summary tabulations will be provided for these assessments 
Stool collection and analysis will be performed for subjects reporting moderate or severe 
diarrhea. Results of the analysis will be listed for each subject. No summary tabulation will be 
provided this assessment. 
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Subject’s body weight will be listed and summarized over all treatment groups. 
 
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13 
REFERENCES 
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14.2 
MG-composite score 
The MG-composite score items and associated scores are provided in Table 14‒2. The total score 
is obtained by summing the responses to each individual item. Thus the score ranges from 0 to 
50.  
In the event of missing data at a particular time point, the MG-composite score will not be 
calculated. Due to the different weighting applied to each item it is not possible to impute the 
missing data with the average score across the remaining items. 
Table 14‒2: MG-composite score items and scoring algorithm 
Item 
Result/Grade 
Result/Grade 
Result/Grade 
Result/Grade 
Ptosis, upward 
gaze (physician 
examination) 
>45 seconds/0 
11-45 seconds/1 
1-10 seconds/2 
Immediate/3 
Double vision on 
lateral gaze, left or 
right (physician 
examination) 
>45 seconds/0 
11-45 seconds/1 
1-10 seconds/3 
Immediate/4 
Eye closure 
(physician 
examination) 
Normal/0 
Mild weakness 
(can be forced 
open with effort)/0 
Moderate 
weakness (can be 
forced open 
easily)/1 
Severe weakness 
(unable to keep 
eyes closed)/2 
Talking (patient 
history) 
Normal/0 
Intermittent 
slurring or nasal 
speech/2 
Constant slurring 
or nasal but can be 
understood/4 
Difficult to 
understand 
speech/6 
Chewing (patient 
history) 
Normal/0 
Fatigue with solid 
food/2 
Fatigue with soft 
food/4 
Gastric tube/6 
Swallowing 
(patient history) 
Normal/0 
Rare episode of 
choking or trouble 
swallowing/2 
Frequent trouble 
swallowing eg, 
necessitating 
changes in diet/5 
Gastric tube/6 
Breathing (thought 
to be caused by 
MG) 
Normal/0 
Shortness of breath 
with exertion/2 
Shortness of breath 
at rest/4 
Ventilator 
dependence/9 
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Item 
Result/Grade 
Result/Grade 
Result/Grade 
Result/Grade 
Neck flexion or 
extension 
(weakest) 
(physician 
examination)
a 
Normal/0 
Mild weakness/1 
Moderate 
weakness (ie, 50% 
weak, +/-15%)/3 
Severe weakness/4 
Shoulder 
abduction 
(physician 
examination) a 
Normal/0 
Mild weakness/2 
Moderate 
weakness (ie, 50% 
weak, +/-15%)/4 
Severe weakness/5 
Hip flexion 
(physician 
examination) a 
Normal/0 
Mild weakness/2 
Moderate 
weakness (ie, 50% 
weak, +/-15%)/4 
Severe weakness/5 
a Moderate weakness for head and neck items should be construed as weakness that equals roughly 50%+/-15% of 
expected normal strength. Any weakness milder than that would be mild and any weakness more severe than that 
would be classified as severe. 
14.3 
MG-Activities of Daily Living 
The MGADL testing form is provided in Table 14‒3. The total score is obtained by summing the 
responses to each individual item. Thus the score ranges from 0 to 24.  
In the event of missing data the following rules will be applied: 
 If 1 or 2 items are not answered, the overall score will be obtained by imputing the missing 
items with the average score across the remaining items at the specific visit. The imputed 
value will be rounded to one decimal place 
 If more than 2 items are missing the overall score will not be calculated 
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14.5 
MG-Impairment Index 
The MG-II is provided in Table 14‒6. The MGII can be summarized as a total score and also as 
2 sub-scores reflecting an Ocular and a Generalized domain. 
The total score is the raw sum of all the items, including the clinical examination and the patient-
reported questionnaire. 
The ocular score is calculated by summing 8 items reflecting ocular impairments. These items 
are: patient questionnaire items 1 to 6 and examination items 1 and 2. 
The generalized score is calculated by adding items 7 to 22 from the patient questionnaire and 
items 3 to 6 from the examination. 
For missing answers, impute the average score for the other items in the same domain or region 
(ocular, or generalized). Only calculate the total sum-score when there are ≤ 3 items missing. 
 
 
 
 
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14.6 
TEMA/PCS criteria for Rozanolixizumab program 
TEMA/PCS criteria for the clinical studies within the Rozanolixizumab clinical development 
program. These values are based on the CTCAE criteria version 4.03, grade 3 toxicity definitions 
and have been adapted to study needs. 
Table 14-7: TEMA/PCS  Values for Rozanolixizumab Clinical Development 
Program Based on CTCAE Grades 
Domain 
Term 
Test 
Criteria 
Unit 
Biochemistry 
Hypoalbuminemia 
Albumin 
<2  
g/dL 
Biochemistry 
Alkaline 
phosphatase 
increased 
ALP 
>5xULN 
n/a 
Biochemistry 
Alanine 
aminotransferase 
increased 
ALT 
>5xULN 
n/a 
Biochemistry 
Serum Amylase 
increased 
Amylase 
>2xULN 
n/a 
Biochemistry 
Aspartate 
aminotransferase 
increased 
AST 
>5xULN 
n/a 
Biochemistry 
Blood bilirubin 
increased 
Bilirubin 
>3 x ULN 
n/a 
Biochemistry 
Hypercalcemia 
Calcium 
corrected >13.5 (>3.1); 
ionized (>1.8) 
mg/dL 
(mmol/L) 
Biochemistry 
Hypocalcemia 
Calcium 
corrected <7 (<1.75); 
ionized (<0.9) 
mg/dL 
(mmol/L) 
Biochemistry 
Cholesterol high 
Cholesterol  
>400 (>10.34) 
mg/dL 
(mmol/L) 
Biochemistry 
Creatine 
phosphokinase 
increased 
CK 
>5xULN 
n/a 
Biochemistry 
Creatinine 
increased 
Creatinine 
>3x baseline or >3 x ULN 
n/a 
Biochemistry 
Acute kidney 
injury 
Creatinine 
>3x baseline or >4 x ULN 
n/a 
Biochemistry 
Chronic kidney 
disease 
eGFR or CrCl 
<=29 
ml/min/1.73
m2 
Biochemistry 
GGT increased 
GGT 
>5xULN 
n/a 
Biochemistry 
Hyperglycemia 
Glucose 
>250 (>13.9) 
mg/dL 
(mmol/L) 
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Table 14-7: TEMA/PCS  Values for Rozanolixizumab Clinical Development 
Program Based on CTCAE Grades 
Domain 
Term 
Test 
Criteria 
Unit 
Biochemistry 
Hypoglycemia 
Glucose 
<40 (<2.2) 
mg/dL 
(mmol/L) 
Biochemistry 
Hypermagnesemia 
Magnesium 
>3 (>1.23) 
mg/dL 
(mmol/L) 
Biochemistry 
Hypomagnesemia 
Magnesium 
<0.9 (<0.4) 
mg/dL 
(mmol/L) 
Biochemistry 
Hypophosphatemi
a 
Phosphate 
<2 (0.6) 
mg/dL 
(mmol/L) 
Biochemistry 
Hyperkalemia 
Potassium 
>6 
mmol/L 
Biochemistry 
Hypokalemia 
Potassium 
<3 
mmol/L 
Biochemistry 
Hypernatremia 
Sodium 
>155 
mmol/L 
Biochemistry 
Hyponatremia 
Sodium  
<130 
mmol/L 
Biochemistry 
Hypertriglyceride
mia 
Triglycerides 
>500 (>5.7) 
mg/dL 
(mmol/L) 
Biochemistry 
Hyperuricemia 
Uric acid 
n/a 
n/a 
Body parameters 
Obesity  
BMI 
>=30 
kg/m2 
ECG 
QT corrrected 
interval prolonged 
(Bazett) 
QTcB 
>=501 ms OR increase 
>=60 ms compared to 
Baseline 
ms 
ECG 
QT corrrected 
interval prolonged 
(Fridericia) 
QTcF 
>=501 ms OR increase 
>=60 ms compared to 
Baseline 
ms 
ECG 
PR prolongation 
PR 
>=210 ms AND >=10 ms 
change from Baseline 
ms 
Haematology 
Anaemia  
Hemoglobin  
<8 (<4.9) 
g/dL 
(mmol/L) 
Haematology 
Haemoglobin 
increased 
Hemoglobin  
increase >4 over ULN or 
increase >4 above Baseline 
(if Baseline is above ULN) 
mg/dL 
Haematology 
Lymphocyte count 
decreased 
Lymphocytes 
<500 (<0.5) 
/mm3 
(109/L) 
Haematology 
Lymphocyte count 
increased 
Lymphocytes 
>20,000 (>20) 
/mm3 
(109/L) 
Haematology 
Neutrophil count 
decreased 
Neutrophils 
<1000 (<1) 
/mm3 
(109/L) 
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Table 14-7: TEMA/PCS  Values for Rozanolixizumab Clinical Development 
Program Based on CTCAE Grades 
Domain 
Term 
Test 
Criteria 
Unit 
Haematology 
Platelet count 
decreased 
Platelets 
<50,000 (<50) 
/mm3 
(109/L) 
Haematology 
Leukocytosis 
WBC 
>20,000 
/mm3 
Haematology 
White blood cell 
decreased 
WBC 
<2000 (<2) 
/mm3 
(109/L) 
Haematology 
Monocytes 
increased 
Monocytes 
>2000 (>2) 
/mm3 
(109/L) 
Vital Signs 
Hypertension 
Blood pressure 
systolic 
≥180 and an increase from 
Baseline of ≥15 
mmHg 
Vital Signs 
Hypertension 
Blood pressure 
diastolic 
>105 and an increase from 
Baseline of ≥ 15 
mmHg 
Vital Signs 
Hypotension 
Blood pressure 
systolic 
≤90 and a decrease from 
Baseline of ≥20 
mmHg 
Vital Signs 
Hypotension 
Blood pressure 
diastolic 
<50 and a decrease from 
Baseline of ≥15 
mmHg 
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15 
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN 
(SAP) (IF APPLICABLE) 
15.1 
Amendment 1 
15.1.1 
Rationale for the amendment 
Amendment 1 is added to include TEMA/PCS for laboratory measurements as well as ECGs and 
to substitute the already incorporated vital sign thresholds. 
In addition small textual changes have been made. 
15.1.2 
Specific changes: 
Change #1 
In section 3.1 treatment groups for observation period were updated to include observation 
periods for subjects withdrawn after period 1. 
Old text 
For Dosing Period 2 and the Observation Period the following Treatment Groups will be 
considered for analysis: 
 Placebo - UCB7665 7mg/kg 
 Placebo - UCB7665 4mg/kg 
 UCB7665 7mg/kg - UCB7665 7mg/kg 
 UCB7665 7mg/kg - UCB7665 4mg/kg 
New text 
For Dosing Period 2 and the Observation Period the following treatment groups will be 
considered for analysis and will be displayed as such in the TFLs (the first two groups will only 
be utilized, for observation period, in case patients do not receive any dosing in period 2):  
 Placebo  
 UCB7665 7mg/kg 
 Placebo - UCB7665 7mg/kg  
 Placebo - UCB7665 4mg/kg 
 UCB7665 7mg/kg - UCB7665 7mg/kg 
 UCB7665 7mg/kg - UCB7665 4mg/kg 
Change #2 
In section 3.6 treatment groups for observation period were updated to include observation 
periods for subjects withdrawn after period 1. 
Old text 
For Dosing Period 2 and the Observation Period the following Treatment Groups will be 
considered for analysis: 
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 Placebo - UCB7665 7mg/kg 
 Placebo - UCB7665 4mg/kg 
 UCB7665 7mg/kg - UCB7665 7mg/kg 
 UCB7665 7mg/kg - UCB7665 4mg/kg 
New text 
For Dosing Period 2 and the Observation Period the following treatment groups will be 
considered for analysis and will be displayed as such in the TFLs (the first two groups will only 
be utilized, for observation period, in case patients do not receive any dosing in period 2):  
 Placebo  
 UCB7665 7mg/kg 
 Placebo - UCB7665 7mg/kg  
 Placebo - UCB7665 4mg/kg 
 UCB7665 7mg/kg - UCB7665 7mg/kg 
 UCB7665 7mg/kg - UCB7665 4mg/kg 
Change #3 
In section 6.1 the population for summarizing demographic characteristics was updated; 
Old text 
All demographic characteristics obtained at the Screening visit will be summarized for the ES 
(apart from the date of birth). 
New text 
All demographic characteristics obtained at the Screening visit will be summarized for the RS 
(apart from the date of birth). 
Change #4 
In section 6.1 the following sentence was added; 
The demographic characteristics listing will include a flag for BMI values identified as 
TEMA/PCS as defined by the criteria outlined in Table 14-7. 
Change #5 
Section 6.2 “Other Baseline characteristics” was added. 
Change #6 
In section 8.3.7, clinically meaningful improvement was defined. 
Change #7 
In section 11, treatment groups were updated as observation periods will be displayed for 
subjects withdrawn after period 1. 
 
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Change #8 
In section 11.1 the following sentence were added; 
In Dosing Period 1 subjects will be randomized (1:1) to receive one of the following treatments: 
 3 sc doses of UCB7665 7mg/kg at 1 week intervals 
 3 sc doses of placebo at 1 week intervals 
In Dosing Period 2 subjects will be rerandomized (1:1) to receive one of the following 
treatments: 
 3 sc doses of UCB7665 7mg/kg at 1 week intervals 
 3 sc doses of UCB7665 4mg/kg at 1 week intervals 
The randomization in Dosing Period 2 will be stratified by the treatment received in Dosing 
Period 1. 
Change #9In section 11.3 the following sentence was added; 
In addition, the listings will include a flag for values identified as TEMA/PCS as defined by the 
criteria outlined in Table 14-7. 
Change #10 
In section 11.3.1 the potential drug-induced liver injury (PDILI) criteria were updated as follows; 
Old text 
 Alanine aminotransferase (ALT) ≥3x ULN or ≥2x baseline value 
 Aspartate aminotransferase (AST) ≥3x ULN or ≥2x baseline value 
 Total bilirubin ≥2x ULN 
New text 
 Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥5x Upper limit of 
normal (ULN)   
 ALT or AST increase ≥3x ULN and Total bilirubin ≥2x ULN 
 ALT or AST ≥3x ULN who exhibit temporally associated symptoms of hepatitis or 
hypersensitivity 
 ALT or AST ≥3xULN (and ≥2x Baseline) and <5xULN, total bilirubin <2xULN, and no 
eosinophilia (i.e., ≤5%), with no fever, rash, or symptoms of hepatitis. 
Change #11 
In section 11.4 a paragraph was updated as below and table 11-2 was deleted. 
Old text 
The listing will include a flag for measurements identified as treatment-emergent markedly 
abnormal (TEMA)/potentially clinically significant (PCS) as per criteria outlined in Table 11‒2. 
New text 
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The listing will include a flag for values identified as TEMA/PCS as defined by the criteria 
outlined in Table 14-7. 
Change #12 
In section 11.4.2 text was updated as below. 
Next text 
The following variables will be reported: 
 Heart rate 
 RR interval 
 PQ/PR interval 
 QRS duration 
 QT interval 
 QT corrected for heart rate using Bazett’s formula (QTcB = QT/RR1/2) 
 QT corrected for heart rate using Fridericia’s formula (QTcF = QT/RR1/3) 
The listing will also include a flag for values identified as TEMA/PCS as defined by the criteria 
outlined in Table 14-7. 
Deleted text 
The frequency of ECG outliers, defined as QTc>480 or QTc change from baseline >30, will be 
summarized by treatment group and time point. 
Change #13 
Section 14.6 was added. 
Change #14 
Section 6.2 was updated; including past medications and providing clarity about summaries to be 
produced. 
 
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STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution. 
 
 
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Approval Signatures
Name:
MG0002-sap-amendment-final 1.0_20180620
Version:
1. 0
Document Number:
CLIN-000122111
Title:
MG0002-sap-amendment-final 1.0_20180620
Approved Date:
10 Jul 2018
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 26-Jun-2018 09:15:02 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 10-Jul-2018 09:52:34 GMT+0000
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