Conditions: Primary Immune Thrombocytopenia
Keywords: ITP UCB7665 Rozanolixizumab Primary immune thrombocytopenia
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 43
Healthy volunteers: no

Brief summary:
The purpose of this study is to assess the long-term safety, tolerability and clinical efficacy of treatment with rozanolixizumab.

Detailed description:

Arms:
arm 1: All study participants will receive fixed-unit doses of rozanolixizumab across body weight tiers at pre-specified time points during the Treatment Period. Doses will be adjusted based on platelet count values or medical needs.

Interventions: intervention 1: Rozanolixizumab
Intervention descriptions: intervention 1: Study participants receive rozanolixizumab by subcutaneous infusion during the Treatment Period.

Protocol document:
Prot_000.pdf: 
UCB 
 
04 Apr 2022 
Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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Page 1 of 199 
AN OPEN-LABEL EXTENSION STUDY TO INVESTIGATE THE 
LONG-TERM SAFETY, TOLERABILITY, AND EFFICACY OF 
ROZANOLIXIZUMAB IN STUDY PARTICIPANTS WITH 
PERSISTENT OR CHRONIC PRIMARY IMMUNE 
THROMBOCYTOPENIA (ITP)  
PROTOCOL TP0004 AMENDMENT 4 
 
Short title: 
A Phase 3 study evaluating the long-term safety, tolerability, and efficacy of rozanolixizumab in 
study participants with ITP 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
  
  
 
 
  
  
Regulatory agency identifying number: 
Eudra CT Number: 
2019-000883-40 
IND Number 
143499  
NCT Number 
NCT04596995 
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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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document History 
Document 
Date 
Type of amendment 
Protocol Amendment 4 
04 Apr 2022 
Non-substantial 
Protocol Amendment 3 
09 Dec 2021 
Non-substantial 
Protocol Amendment 2b 
03 Dec 2021 
Substantial 
Protocol Amendment 1.1 
(China) 
01 Jul 2021 
Substantial 
Protocol Amendment 1a 
11 May 2021 
Substantial 
Protocol Amendment 0.3 
(China) 
04 Feb 2021 
Substantial 
Protocol Amendment 0.2 
(France) 
04 Feb 2021 
Substantial 
Protocol Addendum A 
(UK) 
26 Oct 2020 
Not applicable 
Protocol Amendment 0.1 
(Japan)  
03 Jun 2020 
Substantial 
Original Protocol 
21 Nov 2019 
Not applicable 
a Protocol Amendment 1 was not submitted to all regulatory authorities prior to submission of 
Protocol Amendment 2. Details of the changes between the original protocol and protocol 
amendment 1 are provided in Section 10.25. 
b Protocol Amendment 2 was not submitted to any regulatory authorities prior to issuance of 
Protocol Amendment 3.  
Amendment 4 (04 Apr 2022) 
Overall Rationale for the Amendment 
The primary reason for this protocol amendment is to correct errors and inconsistencies from 
Protocol Amendment 3.  
This amendment is considered to be non-substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European 
Union. 
Section # and Name 
Description of Change 
Brief Rationale 
Global 
Minor administrative, consistency, 
formatting and typographical 
changes have been made. 
Updated to provide clarity and be 
consistent with remainder of 
protocol. 
Global  
Reference to 
 when 
describing the safety of the study 
drug has been amended to “well 
To acknowledge the common 
industry codes, the description of 
the study drug has been updated 
from 
 and well tolerated” to 
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Section # and Name 
Description of Change 
Brief Rationale 
tolerated, with an acceptable safety 
profile” instead. 
“well tolerated with an acceptable 
safety profile.” 
1.1 Synopsis, Overall 
Design 
Paragraph #4 was updated to 
clarify that all study participants 
will receive rozanolixizumab at the 
assigned dose level from the parent 
study, if the platelet count was 
between ≥50×109/L and 
≤150×109/L. 
Updated for clarity. 
1.3 Schedule of activities  
“W13 and W25 only” was removed 
from the Visit column for 
laboratory parameters. A new 
footnote m was added to clarify 
that samples for total cholesterol, 
LDL, HDL, and triglycerides will 
be collected at Weeks 13 and 25 
only. Subsequent footnotes were 
reorganized.  
 
Footnote j was updated to state 
EOS Visit (Week 60). 
 
Footnote r was added to all dosing 
visits.  
Blood samples are taken every 
4 weeks for safety assessments. 
Analysis of total cholesterol, LDL, 
HDL, and triglycerides will be 
done at Weeks 13 and 25 only.  
 
 
 
 
 
Updated for consistency and to 
correct an error.  
 
Updated for clarity. 
2.1 Study rationale  
 was replaced with “well-
tolerated” in paragraph #5.  
To acknowledge the common 
industry codes, the description of 
the study drug has been updated 
from 
to “well tolerated.” 
3 Objectives and endpoints  One of the other safety endpoints, 
“Changes from Baselinea in 
concentrations of total protein, 
albumin, α-globulin, and β-
globulin”, was updated to remove 
α-globulin and β-globulin.  
 
One of the other efficacy endpoints, 
"Stable Response defined as 
platelet count ≥30×109/L and 
absence of bleedingb without rescue 
therapy at ≥70% of the visits over 
the planned 52-week Treatment 
Period at Week 4" was updated to 
“starting at Week 4.”  
 
One of the other secondary efficacy 
endpoints, “Change from Baselinea 
to Week 54 including all 
Updated for consistency to Section 
1.1. 
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Section # and Name 
Description of Change 
Brief Rationale 
intermediate timepoints for ITP-
PAQ Symptoms domain score” was 
updated to “Change from Baselinea 
to Week 53 including all 
intermediate timepoints for ITP-
PAQ Symptoms domain score.” 
4.1 Overall design  
Paragraph #3 was updated to 
clarify that all study partcipants 
will receive rozanolixizumab at the 
assigned dose level from the parent 
study, if the platelet count was 
between ≥50×109/L and 
≤150×109/L. 
Updated for clarity.   
4.1 Overall design 
Table 4-2 and Figure 4-1 were 
updated to clarify the dose 
adjustments for platelet count 
results of ≥10×109/L to <30×109/L 
(on at least two consecutive visits) 
and <10×109/L. 
Updated for clarity. 
4.1 Overall design 
A sentence was added to the dose 
adjustments paragraph to state: If a 
study participant has been down-
titrated to a fixed-unit dose 
equivalent to 
 or the 
 
total dose (corresponding to an 
average
 dose in a 
participant weighing 70kg), and 
platelet count decreases to 
<50×109/L, then up-titration to a 
fixed-unit dose equivalent to 
 or 
 
respectively, would be allowed. 
Updated for clarity. 
6.4.3.1 Rescue therapy not 
leading to discontinuation  
Bullet point #2 was updated to 
remove reference to “intravenous” 
and “steroids” was updated to 
“corticosteroids.” 
Updated for consistency. 
6.4.3.2 Rescue therapy 
leading to discontinuation 
Bullet point #4: “steroids” was 
updated to “corticosteroids.” 
Updated for consistency. 
6.7 Home visits  
The requirement for stable platelet 
count “during the last two dosing 
visits” was updated to “during the 
last four dosing visits.”  
Platelet count result between 50 to 
150×109/L was corrected to 
between ≥50 to ≤150×109/L. 
Updated for consistency and to 
correct errors. 
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Section # and Name 
Description of Change 
Brief Rationale 
8.1.5.1 Tuberculosis 
assessment 
Reference to the TB questionnaire, 
Appendix 18 was corrected.  
Updated for consistency and to 
correct an error. 
10.1.3 Informed consent 
process 
 
Appendix 10.7, Japan 
Japan-specific requirement for 
study participants <20 was 
removed.  
Since 01 Apr 2022, the revision to 
the Japan civil code has lowered 
the age of adulthood to 18 from 20. 
Appendix 10.7, France  
Anticipated timelines for 
completing enrollment of all 
participants in the parent studies 
were updated.  
To provide the updated projected 
dates.  
10.9 Appendix 9: 
Abbreviations and 
trademarks 
Additional abbreviations and 
definitions were added for: 
UADE and USADE 
General update.  
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SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h) 
All serious adverse events (SAEs) will be reported and transmitted to Patient 
Safety through the electronic Case Report form (eCRF) system. The numbers 
below are to be used to send ancillary documentation only (eg, discharge 
summaries, death certificates) or in the event that the eCRF is not available. 
Fax 
Europe and Rest of the World: +32 2 386 24 21 
US: +1 800 880 6949  or +1 866 890 3175  
Email 
Global (for interventional clinical studies): DS_ICT@ucb.com 
 
Serious adverse event (investigational device) and  
device deficiency reporting (24h)  
Fax: 
Japan: +81 3 6864 7400 
Email: 
Japan: UCBJ-Safety@ucb.com 
 
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TABLE OF CONTENTS 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ...................................... 2 
SERIOUS ADVERSE EVENT REPORTING .......................................................................... 6 
1 
PROTOCOL SUMMARY ............................................................................................... 12 
1.1 Synopsis ........................................................................................................................... 12 
1.2 Schema ............................................................................................................................. 17 
1.3 Schedule of Activities ...................................................................................................... 19 
2 
INTRODUCTION ........................................................................................................... 32 
2.1 Study rationale ................................................................................................................. 32 
2.2 Background ...................................................................................................................... 34 
2.3 Benefit/risk assessment .................................................................................................... 35 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 38 
4 
STUDY DESIGN ............................................................................................................. 42 
4.1 Overall design .................................................................................................................. 42 
4.2 Scientific rationale for study design................................................................................. 46 
4.3 Justification for dose ........................................................................................................ 46 
4.4 End of study definition ..................................................................................................... 47 
5 
STUDY POPULATION .................................................................................................. 47 
5.1 Inclusion criteria .............................................................................................................. 48 
5.2 Exclusion criteria ............................................................................................................. 48 
5.3 Lifestyle restrictions ......................................................................................................... 50 
6 
STUDY TREATMENTS ................................................................................................. 50 
6.1 Preparation, handling, storage, and accountability requirements .................................... 50 
6.1.1 
Drug accountability ............................................................................................. 51 
6.2 Measures to minimize bias: randomization ..................................................................... 51 
6.3 Treatment compliance ...................................................................................................... 51 
6.4 Concomitant medications/treatments ............................................................................... 52 
6.4.1 
Permitted concomitant treatments (medications and therapies) .......................... 52 
6.4.2 
Prohibited concomitant treatments (medications and therapies) ......................... 52 
6.4.3 
Rescue therapy ..................................................................................................... 53 
6.4.3.1 
Rescue therapy not leading to discontinuation .......................................... 53 
6.4.3.2 
Rescue therapy leading to discontinuation ................................................ 54 
6.5 Dose modification ............................................................................................................ 54 
6.6 Self-administration ........................................................................................................... 54 
6.7 Home visits ...................................................................................................................... 55 
6.8 Treatment after the end of the study ................................................................................ 55 
7 
DISCONTINUATION OF IMP AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 55 
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7.1 Discontinuation of IMP .................................................................................................... 55 
7.1.1 
Liver chemistry stopping criteria ......................................................................... 55 
7.1.2 
QTc stopping criteria ........................................................................................... 57 
7.1.3 
Discontinuation of IMP due to other adverse events or medical condition ......... 58 
7.1.4 
Temporary IMP discontinuation .......................................................................... 59 
7.2 Participant discontinuation/withdrawal from the study ................................................... 59 
7.3 Lost to follow-up .............................................................................................................. 60 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 60 
8.1 Safety assessments ........................................................................................................... 61 
8.1.1 
Physical examination ........................................................................................... 61 
8.1.2 
Vital signs ............................................................................................................ 62 
8.1.3 
Electrocardiograms .............................................................................................. 62 
8.1.4 
Clinical safety laboratory assessments ................................................................ 62 
8.1.5 
Assessment and management of TB and TB risk factors .................................... 63 
8.1.5.1 
Tuberculosis assessment ............................................................................ 63 
8.1.5.2 
Tuberculosis management ......................................................................... 63 
8.1.6 
Splenectomized study participants ...................................................................... 64 
8.2 Adverse events ................................................................................................................. 65 
8.2.1 
Time period and frequency for collecting AE and SAE information .................. 65 
8.2.2 
Method of detecting AEs and SAEs .................................................................... 65 
8.2.3 
Follow-up of AEs and SAEs ................................................................................ 65 
8.2.4 
Regulatory reporting requirements for SAEs ...................................................... 66 
8.2.5 
Pregnancy ............................................................................................................ 66 
8.2.6 
Anticipated serious adverse events ...................................................................... 66 
8.2.7 
Adverse events of special interest ........................................................................ 67 
8.2.8 
Adverse events of special monitoring .................................................................. 67 
8.2.9 
COVID-19 vaccination ........................................................................................ 67 
8.3 Safety signal detection ..................................................................................................... 68 
8.4 Treatment of overdose ..................................................................................................... 68 
8.5 Efficacy assessments ........................................................................................................ 68 
8.5.1 
Platelet counts ...................................................................................................... 68 
8.5.2 
ITP bleeding score ............................................................................................... 69 
8.5.3 
Patient Reported Outcomes ................................................................................. 70 
8.5.3.1 
ITP-PAQ .................................................................................................... 70 
8.5.3.2 
SF-36 ......................................................................................................... 70 
8.5.3.3 
FATIGUE-PRO Physical Fatigue Scale .................................................... 70 
8.5.3.4 
EQ-5D-5L .................................................................................................. 71 
8.5.3.5 
PGI-S ......................................................................................................... 71 
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8.5.3.6 
PGI-C ......................................................................................................... 71 
8.5.3.7 
SIAQ (Infusion version) ............................................................................ 71 
8.6 Pharmacokinetics and antidrug antibodies ....................................................................... 72 
8.7 Pharmacodynamics .......................................................................................................... 72 
8.8 Exploratory biomarkers ................................................................................................... 73 
8.9 Immunology biomarkers .................................................................................................. 73 
8.10 Medical resource utilization and health economics ......................................................... 73 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 74 
9.1 Definition of analysis sets ................................................................................................ 74 
9.2 General statistical considerations ..................................................................................... 74 
9.3 Estimands ......................................................................................................................... 74 
9.4 Planned safety analyses .................................................................................................... 75 
9.5 Planned efficacy/outcome analyses ................................................................................. 75 
9.6 Planned other analyses ..................................................................................................... 76 
9.6.1 
Analysis of pharmacodynamics endpoints .......................................................... 76 
9.6.2 
Analysis of pharmacokinetics endpoints ............................................................. 76 
9.6.3 
Antidrug antibodies analyses ............................................................................... 76 
9.7 Handling of protocol deviations ....................................................................................... 77 
9.8 Handling of dropouts or missing data .............................................................................. 77 
9.9 Planned interim analysis, data monitoring, and data snapshots ....................................... 77 
9.9.1 
Interim analysis .................................................................................................... 77 
9.9.2 
Data monitoring ................................................................................................... 77 
9.9.3 
Data snapshots ..................................................................................................... 77 
9.10 Determination of sample size ........................................................................................... 77 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 78 
10.1 Appendix 1: Regulatory, ethical, and study oversight considerations ............................. 78 
10.1.1 
Regulatory and ethical considerations ................................................................. 78 
10.1.2 
Financial disclosure ............................................................................................. 78 
10.1.3 
Informed consent process .................................................................................... 79 
10.1.4 
Data protection ..................................................................................................... 79 
10.1.5 
Committees structure ........................................................................................... 80 
10.1.6 
Data quality assurance ......................................................................................... 80 
10.1.6.1 
Electronic Case Report form completion .................................................. 80 
10.1.6.2 
Apps ........................................................................................................... 81 
10.1.7 
Source documents ................................................................................................ 81 
10.1.8 
Study and site closure .......................................................................................... 81 
10.1.9 
Publication policy ................................................................................................ 82 
10.2 Appendix 2: Clinical laboratory tests .............................................................................. 83 
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10.3 Appendix 3: Adverse events – definitions and procedures for recording, evaluating, 
follow-up, and reporting .................................................................................................. 85 
10.3.1 
Definition of AE .................................................................................................. 85 
10.3.2 
Definition of SAE ................................................................................................ 86 
10.3.3 
Recording and Follow-up of AE and/or SAE ...................................................... 87 
10.3.4 
Reporting of SAEs ............................................................................................... 89 
10.4 Appendix 4: Contraceptive guidance and collection of pregnancy information ............. 91 
10.5 Appendix 5: Liver safety – suggested actions and follow-up assessments ..................... 94 
10.6 Appendix 6: Medical device incidents – definition and procedures for recording, 
evaluating, follow-up, and reporting ................................................................................ 97 
10.7 Appendix 7: Country-specific requirements .................................................................... 98 
Poland 
98 
France 
98 
Japan 
98 
10.7.1 
Countries where self-administration will be offered as an option ..................... 104 
10.8 Appendix 8: Rapid alert procedures .............................................................................. 105 
10.9 Appendix 9: Abbreviations and trademarks .................................................................. 106 
10.10 
Appendix 10: ITP-BAT ....................................................................................... 109 
10.11 
Appendix 11: ITP-PAQ ....................................................................................... 119 
10.12 
Appendix 12: SF-36 Form ................................................................................... 130 
10.13 
Appendix 13: FATIGUE-PRO Physical Fatigue Scale ....................................... 136 
10.14 
Appendix 14: EQ-5D-5L ..................................................................................... 137 
10.15 
Appendix 15: PGI-S ............................................................................................. 139 
10.16 
Appendix 16: PGI-C ............................................................................................ 140 
10.17 
Appendix 17: Headache Questionnaire ............................................................... 141 
10.18 
Appendix 18: Tuberculosis assessment ............................................................... 145 
10.19 
Appendix 19: Sampson Criteria Questionnaire ................................................... 146 
10.20 
Appendix 20: Management of headache .............................................................. 147 
10.21 
Appendix 21: Management of diarrhea ............................................................... 149 
10.22 
Appendix 22: Management of infections and hypogammaglobulinemia ............ 150 
Dose adjustments/dose skipped ......................................................................................... 151 
Splenectomized Study Participants .................................................................................... 151 
10.23 
Appendix 23: Management of infusion-related reactions or hypersensitivity 
reactions ......................................................................................................................... 153 
10.24 
Appendix 24: SIAQ (infusion version) ................................................................ 155 
10.25 
Appendix 25: Protocol Amendment History ....................................................... 162 
11 REFERENCES .............................................................................................................. 197 
SPONSOR DECLARATION ................................................................................................ 199 
 
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LIST OF TABLES 
Table 1-1: 
Schedule of activities ....................................................................................... 19 
Table 4-1: 
TP0004 dose levels and weight tiers of IMP ................................................... 43 
Table 4-2: 
Dose adjustments of rozanolixizumab ............................................................. 44 
Table 6-1: 
Treatments administered .................................................................................. 50 
Table 6-2: 
Permitted concomitant treatments (medications and therapies) ...................... 52 
Table 8-1: 
Anticipated serious adverse events for ITP population ................................... 66 
Table 10-1: 
Protocol-required safety laboratory assessments ............................................. 83 
Table 10-2: 
Highly effective contraceptive methodsa ......................................................... 92 
Table 10-3: 
Phase 3 or 4 liver chemistry stopping criteria and follow-up assessments ...... 94 
Table 10-4: 
Phase 3-4 liver chemistry increased monitoring criteria with continued 
IMP .................................................................................................................. 96 
Table 10-5: 
ITP-Bleeding Assessment Tool ..................................................................... 109 
Table 10-6: 
Headache Questionnaire ................................................................................ 141 
Table 10-7: 
Management of infections and hypogammaglobulinemia ............................. 151 
Table 10-8: 
Suggested management guidelines for infusion reactions ............................. 153 
 
LIST OF FIGURES 
Figure 1-1: 
TP0004 study schematic .................................................................................. 18 
Figure 4-1: 
Dose adjustments of rozanolixizumab ............................................................. 45 
Figure 7-1: 
Phase 3-4 liver chemistry stopping criteria and increased monitoring 
algorithm .......................................................................................................... 56 
Figure 7-2: 
Liver chemistry increased monitoring algorithm with continued study 
intervention for participants with ALT ≥3xULN but <8xULN ....................... 57 
 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title: 
An open-label extension study to investigate the long-term safety, tolerability, and efficacy of 
rozanolixizumab in study participants with persistent or chronic primary immune 
thrombocytopenia (ITP). 
Short Title: 
A Phase 3 study evaluating the long-term safety, tolerability, and efficacy of rozanolixizumab in 
study participants with primary ITP. 
Rationale: 
Immune thrombocytopenia is a clinical disorder in which thrombocytopenia manifests as a 
bleeding tendency, purpura, or petechiae. Autoantibodies against platelet antigens are considered 
to be a hallmark of ITP. Production of pathogenic immunoglobulin (Ig)G autoantibodies by 
plasma cells is accepted as the central underlying pathophysiological mechanism in a number of 
IgG-mediated autoimmune diseases, which includes ITP. In some patients, antibodies recognize 
antigens derived from a single glycoprotein, whereas in others, antibodies recognize multiple 
glycoproteins. The spleen is the key organ in the pathophysiology of ITP, not only because 
platelet autoantibodies are formed in the white pulp, but also because mononuclear macrophages 
in the red pulp destroy immunoglobulin-coated platelets. 
Treatments aimed at reducing the quantity of circulating IgG autoantibodies are being used for 
primary and secondary therapy of autoimmune diseases including ITP, particularly where 
corticosteroid-based immune suppression is not or no longer effective. The therapeutic approach 
of these treatments is based on lowering levels of pathogenic autoantibodies, which represents 
rational and effective treatment modalities of autoimmune diseases. The major goal for treatment 
of ITP is to achieve a platelet count that prevents major bleeding rather than correcting the 
platelet count to normal levels. 
Rozanolixizumab is a humanized IgG4P monoclonal antibody that is being developed as an 
inhibitor of the activity of neonatal Fc receptor (FcRn). The FcRn receptor recycles IgG and 
albumin and transports it bidirectionally across epithelial barriers. Recent studies have shown 
that FcRn rescues both IgG and albumin from intracellular lysosomal degradation by recycling it 
from the sorting endosome to the cell surface (Anderson et al, 2006). Rozanolixizumab has been 
specifically designed to block IgG binding to FcRn without blocking the binding and recycling 
of albumin. By blocking the activity of FcRn, rozanolixizumab accelerates the catabolism of IgG 
antibodies, including IgG autoantibodies. TP0003 and TP0006, the parent studies of the current 
open-label extension (OLE) study, TP0004, are designed to evaluate the efficacy, safety, and 
tolerability of rozanolixizumab given as doses equivalent to 
 or 
reduced doses equivalent to 
 or approximately 
 in 
adult study participants with ITP. This study, TP0004, is designed to assess whether repeat 
treatment over a period of 52 weeks with rozanolixizumab sc infusion is well tolerated with an 
acceptable safety profile and will result in platelet increases as a measure of efficacy. Data from 
this study will support the data from the parent studies (TP0003 and TP0006). 
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Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To assess the long-term safety and 
tolerability of treatment with 
rozanolixizumab 
The primary safety endpoints are: 
• Occurrence of treatment-emergent adverse 
events (TEAEs) 
• Occurrence of TEAEs leading to permanent 
withdrawal of rozanolixizumab (ie, study 
discontinuation) 
The other safety endpoints are: 
• Occurrence of treatment-emergent adverse 
events of special monitoring (AESM) 
• Occurrence of serious TEAEs 
• Occurrence of treatment-related TEAEs 
• Vital sign change from Baselinea (blood 
pressure [BP], body temperature, and pulse 
rate) at each scheduled assessment during 
Treatment and Safety Follow-Up (SFU) 
Periods 
• 12-lead electrocardiogram (ECG) change from 
Baselinea at each scheduled ECG assessment 
visit 
• Laboratory change from Baselinea 
(hematology, including coagulation parameters, 
clinical chemistry, and urinalysis) at each 
scheduled assessment during Treatment and 
SFU Periods 
• Changes from Baselinea in concentrations of 
total protein and albumin 
• Changes from Baselinea in serum (C3 and C4) 
and plasma (C3a and C5a) complement levels 
at each scheduled assessment during study (for 
study participants experiencing infusion or 
hypersensitivity reactions) 
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Objectives 
Endpoints 
Secondary 
• To assess the long-term clinical 
efficacy of treatment with 
rozanolixizumab 
The secondary efficacy endpoint is: 
• Stable Clinically Meaningful Response, defined 
as Clinically Meaningful Response (ie, platelet 
count ≥50×109/L) without rescue therapy at 
≥70% of the visits over the planned 52 week 
Treatment Period starting at Week 4 
The other efficacy endpoints are: 
• Stable Response defined as platelet count 
≥30×109/L and absence of bleedingb without 
rescue therapy at ≥70% of the visits over the 
planned 52-week Treatment Period starting at 
Week 4  
• Cumulative number of weeks with Clinically 
Meaningful Response over the 52-week 
Treatment Period 
• Cumulative number of weeks with platelet 
counts ≥30×109/L over the planned 52-week 
Treatment Period 
• Duration of first Clinically Meaningful 
Response starting at Week 4  
• Mean Change from Baselinea in platelet count 
at each visit 
• Use of rescue medication by visit 
• ITP specific Bleeding Assessment Tool (ITP-
BAT) bleeding events and severity by visit  
• To assess the effect of 
rozanolixizumab on study participant 
perceived symptoms 
• Change from Baselinea to Week 53 including 
all intermediate timepoints for ITP-PAQ 
Symptoms domain score 
• To assess the reduction in use of 
steroids and other concomitant ITP 
medications  
• AUC of the oral steroid dose over time 
• Change in dose and/or frequency of 
concomitant ITP medications (excluding 
corticosteroids) over time  
Exploratory 
• To assess the effect of 
rozanolixizumab on patient-reported 
outcomes (PROs) 
• Change from Baselinea in FATIGUE-PRO 
Physical Fatigue Score  
• Change from Baselinea in Patient Global 
Impression of Severity (PGI-S)  
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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Objectives 
Endpoints 
• Patient Global Impression of Change (PGI-C) 
at all available post-Baselinea assessments  
• Change from Baselinea in ITP-Patient 
Assessment Questionnaire (ITP-PAQ) domain 
scores  
• To assess the clinical efficacy of 
rozanolixizumab in study 
participants with first exposure to 
rozanolixizumab 
• In study participants with first exposure to 
rozanolixizumab: Durable Clinically 
Meaningful Platelet Response of ≥50×109/L, 
for at least 4 of 6 
 visits between 
Weeks 13 to 25 of the study 
• In study participants with first exposure to 
rozanolixizumab: Time to first Clinically 
Meaningful Platelet Response of ≥50×109/L: 
time from starting treatment to achievement of 
first response of ≥50×109/L 
• To assess effect of rozanolixizumab 
on health-related quality of life 
(HRQoL) and broader disease 
impact 
• Change from Baselinea in European Quality of 
Life (EuroQol)-5 dimension 5 Levels 
Assessment (EQ-5D-5L) item responses 
• Change from Baselinea in Short-Form 36-Item 
(SF-36) domain and composite scores 
• To assess resource utilization 
• Number and length of hospitalizations 
• Number of infusion center admissions 
• To assess the experience with the 
subcutaneous (sc) self-administration 
• PRE-Self Injection Assessment Questionnaire 
(SIAQ) (Infusion version) domains scores 
before the first sc self-administration in 
participants that self-administer  
• POST-SIAQ (Infusion version) domains scores 
at each available visit in participants that self-
administer 
• To assess the PD effect of 
rozanolixizumab 
• Total serum IgG (absolute value) and change 
from Baselinea (absolute value and percentage) 
in serum IgG and in serum IgG subclass 
concentration at each scheduled assessment 
• Absolute value and change from Baselinea 
(absolute value and percentage) in serum Ig 
concentrations (IgA, IgE, IgM) at each 
scheduled assessment 
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Clinical Study Protocol Amendment 4 
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Objectives 
Endpoints 
• To evaluate the incidence and 
emergence of antidrug antibody 
(ADA) of rozanolixizumab 
• ADA at each scheduled assessment 
• To assess the pharmacokinetics (PK) 
of rozanolixizumab administered by 
sc infusion 
• Plasma concentrations of rozanolixizumab at 
each scheduled assessment  
• To evaluate clinical response 
following end of dosing   
• Platelet count by visit after end of dosing 
• Time from end of rozanolixizumab dosing to 
loss of clinically relevant response 
• To assess the influence of 
rozanolixizumab treatment on 
vaccination titers 
• Percent change from Baselinea in vaccination 
titers against Streptococcus pneumoniae, 
Neisseria meningitidis, and Haemophilus 
influenzae in splenectomized study participants  
• To assess the effect of 
rozanolixizumab on post-vaccination 
biomarker(s) in study participants 
who received the COVID-19 vaccine 
• Change in post-vaccination biomarker(s) over 
time in study participants who received the 
COVID-19 vaccine  
a Baseline definitions will be detailed in the SAP. 
bAbsence of bleeding indicated by Grade 0 for all domains of the Skin-Visible Mucosa-Internal Organs (SMOG) 
tool, or a Skin Grade of 0 or 1. 
Overall Design 
This is a Phase 3, multicenter, 59-week OLE study of rozanolixizumab in study participants with 
persistent or chronic primary ITP. Study participants from TP0003 and TP0006 who have 
completed the 24-week Treatment Period (irrespective of rescue therapy) and continue to meet 
the eligibility criteria will be offered enrollment into TP0004.  
This study will assess whether continued dosing
 with rozanolixizumab is well tolerated 
with an acceptable safety profile. This study will also assess whether continued rozanolixizumab 
sc infusions 
 over a period of 52 weeks will maintain a durable Clinically Meaningful 
Platelet count of ≥50×109/L. 
The rollover from TP0003 or TP0006 to TP0004 needs to be completed within 3 days after 
Week 25 (Visit 27) of the parent studies at the latest. In case of a late rollover, platelet counts 
will need to be remeasured. 
On Day 1 (Baseline Visit), which corresponds to Week 25 of the parent studies, TP0003 or 
TP0006, all study participants will enter TP0004. All study participants will receive 
rozanolixizumab treatment 
at the assigned dose level at the end of TP0003 or TP0006, if the 
platelet count was between ≥50×109/L and ≤150×109/L. If outside of this range, a higher or 
lower dose level than the final sc infusion in TP0003 or TP0006 is permitted according to 
Table 4-2 and Figure 4-1. Rozanolixizumab will be administered 
 as a sc infusion to 
maintain platelet count ≥50×109/L. Dose levels equivalent to 
 and 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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 total dose (corresponding to an average 
 dose in a participant weighing 70kg) 
 
can be utilized for maintenance treatment.  
If treatment with rozanolixizumab does not lead to an increase in platelet counts ≥30×109/L, 
study participants can be treated with rescue therapy if deemed needed by the investigator. If 
platelet counts are ≥10×109/L to <30×109/L or active bleeding, rescue therapy is recommended 
(eg, commercially available medication, such as intravenous (iv) immunoglobulin (IVIg), high 
dose corticosteroids and pulse steroids, platelet transfusions, or any other medication listed in 
Section 6.4.3). If platelet counts are <10×109/L, rescue therapy is highly recommended as per 
Section 6.4.3. 
An external Independent Data Monitoring Committee (IDMC) will be utilized to review the 
safety data at predefined intervals and ad hoc as needed, should any emerging safety concern 
arise during the study. Key safety data may be pooled at the discretion of the IDMC for 
protection of all study participants if warranted. 
Based on feedback from the IDMC, 
 dosing was implemented in protocol amendment 2. 
Study participants being treated with the 
 dosing regimen will switch to the 
 
dosing regimen once protocol amendment 2 is approved at the respective study site.  
Additionally, the sponsor’s Safety Signal Detection Team will perform aggregated safety data 
reviews at predefined intervals across the rozanolixizumab program. 
Number of Participants 
Based on the number of study participants planned for the parent studies, up to a maximum of 
180 study participants who complete TP0003 or TP0006 may be eligible to enroll in this OLE 
study. 
Treatment Groups and Duration 
Study participants will be treated for a maximum of 52 weeks. After the final dose, study 
participants will be followed in an 8-week SFU Period. The maximum total duration of the study 
for each study participant will be 59 weeks (For France-specific requirements, see Appendix 7, 
Section 10.7). 
1.2 
Schema 
A schematic diagram for the study is presented in Figure 1-1. 
 
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Clinical Study Protocol Amendment 4 
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Figure 1-1: TP0004 study schematic 
 
 SFU=Safety Follow-Up 
 
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1.3 
Schedule of Activities 
Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
Written informed consent 
and written 
pharmacogenomics 
substudy informed 
consent (for participating 
study participants) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Verification of 
inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Study Protocol Amendment 4 
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Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
General 
medical/procedures 
history 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ITP history update  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medication 
Xe 
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 
Urine pregnancy testf 
X 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
X 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
Platelet count (local 
laboratory)g 
Xh 
X 
X 
X 
X 
X 
Xi 
X 
X 
  
X 
Xi 
X 
X 
X 
Withdrawal criteria 
X 
X 
X 
X 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECGj 
Xk 
pre- and 
postdose 
 
 
 
X 
pre-
dose 
 
 
 
 
X pre-
dose 
(W25 
only) 
 
 
 
  
 
X 
Vital signsl 
Xe 
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
X  
X 
 
X 
Body weight  
X 
 
 
 
 
 
 
 
X 
(W25 
only) 
 
 
 
X 
 
X 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
Height 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Full physical 
examination 
Xe 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Short physical 
examination 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
X 
Recording of AEs 
(including 
hospitalizations) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
Laboratory parameters 
(coagulation, 
hematology, chemistry, 
and urinalysis using 
central laboratory) 
Xe 
 
X 
X 
 
X 
 
 
Xm 
 
 
 
 
X 
 
X 
Vaccination titer (in 
splenectomized 
participants) 
Xe 
 
 
 
 
 
 
 
X  
(W25 
only) 
 
 
 
 
 
X 
COVID sample (for 
study participants 
vaccinated prior to entry 
into TP0004)n 
X 
 
 
 
 
 
 
 
X 
(W25 
only) 
 
 
 
 
 
X 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
COVID sample (for 
study participants 
vaccinated during 
enrollment in TP0004) 
Xo 
 
X 
TB signs and symptoms 
questionnairep 
Xe 
 
 
 
 
 
 
 
X 
(W13, 
W25, 
W37, 
W49 only) 
 
 
 
 
 
X 
Contact IRT 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Administration of IMPq 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
Blood sampling for 
plasma concentration of 
rozanolixizumabs 
X 
X 
 
X 
 
X 
 
 
X 
(W17, 
W29, 
W41 only) 
 
 
 
 
 
X 
Anti-rozanolixizumab 
antibodiess 
X 
 
  
X 
 
X 
 
 
X 
(W17, 
W29, 
W41 only) 
 
 
 
 
 
X 
Serum complements (C3 
and C4) and plasma 
complements (C3a and 
C5a)t 
X  
X 
X 
X 
X 
X 
X 
X 
X  
(W33 
only) 
X 
X 
X 
X 
 
 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
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Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
Blood collection for 
DNA and RNAu 
Xe 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Blood collection for 
exploratory biomarker 
analysisv 
Xe 
X 
X 
X 
X 
X 
X 
X 
X 
(W33 
only) 
X 
X 
X 
X 
 
 
Immunoglobulins (total 
IgG, IgG subclasses)w 
Xe 
 
X 
X 
X 
X 
 
X 
X 
 
X 
(W19, 
W23 
only)  
 
 
X 
X 
IgA, IgM, IgE 
Xe 
 
X 
 
 
X 
 
 
X (W17, 
W29, 
W41 only) 
 
 
 
X 
 
 
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Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
 
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Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
ITP-specific 
autoantibodies 
Xe 
 
 
X 
 
 
 
 
X (W33 
only) 
 
 
 
 
 
X 
ITP bleeding scale 
Xe 
X 
X 
X 
X 
X 
 
X 
(W7 
and 11 
only) 
X 
 
X 
 
X 
X 
X 
ITP-PAQx 
Xe 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
SF-36x 
Xe 
 
 
 
 
X  
 
 
X (W17, 
W29, 
W41 only) 
 
 
 
X 
 
 
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Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
 
Page 28 of 199  
Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
EQ-5D-5Lx 
Xe 
 
 
 
 
X 
 
 
X (W17, 
W29, 
W41 only) 
 
 
 
X 
 
 
PGI-Cx 
Xe 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
PGI-Sx 
Xe 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
FATIGUE-PRO Physical 
Fatigue Scalex 
Xe 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
Pre-SIAQ (self-infusion)y 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
 
Post-SIAQ (self-
infusion)z 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
 
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Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
 
Page 29 of 199  
Table 1-1: 
Schedule of activities 
Assessmentsa 
 
 
Treatment Period 
SFU Period 
Visitb 
1/ 
BL 
2 
3 
4 
5 
6  
7, 9, 
11, 13,  
8, 12, 
16 
10, 14, 18, 
22, 26, 30, 
34, 38, 42, 
46, 50 
15, 17, 19, 21, 
23, 25, 27, 29, 
31, 33, 35, 37, 
39, 41, 43, 45, 
47, 49, 51, 53 
20, 
24, 
28, 52 
32, 36, 
40, 44, 
48 
54 
55 
56 
EOSc/
EW 
Week 
Day 
Visit 
window 
up to +3 
days 
from 
W25 of 
parent 
study 
+2
d 
±2
dd 
±2d
d 
±2d
d 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
±2dd 
Headache questionnaireaa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
          Site visit 
        Optional home visit: Home IMP administration and assessments are optional and can be conducted (if approved by regulatory agencies). Alternatively, these 
visits can be conducted at the sites, as deemed necessary by site personnel and/or the study participant. 
ADA=antidrug antibody; AE=adverse event; BL=Baseline; BP=blood pressure; d=day(s); DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of 
Study; EQ-5D-5L=European Quality of Life-5 Dimension 5 Levels; EW=Early Withdrawal; GI=gastrointestinal; HCP=healthcare professional; HDL=high-
density lipoprotein; ICF=Informed Consent form; Ig=immunoglobulin; IMP=investigational medicinal product; IRT=interactive response technology; 
ITP=immune thrombocytopenia; ITP-PAQ=ITP-Patient Assessment Questionnaire; LDL=low-density lipoprotein; PGI-C=Patient Global Impression of Change; 
PGI-S=Patient Global Impression of Severity; PK=pharmacokinetic; RNA=ribonucleic acid; SF-36=Short-Form 36-Item Health Survey; SFU=Safety Follow-up; 
TB=tuberculosis 
a  The allowed time window for assessments is ±5 mins for assessments <30 mins and ±15 mins for assessments >30 mins.  
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b  Home visits, if possible, are applicable for the individual site at the Weeks displayed in the grey columns. Home visits will be performed by a healthcare 
professional (HCP) visiting the study participant at his/her home. Alternately, the visits can be conducted at the site as deemed necessary by site and/or study 
participant. Feasibility of IMP dosing in a home setting will have to be confirmed before the visit is conducted (see Section 6.7).   
c  The EOS Visit is 8 weeks following the final dose of rozanolixizumab. 
d  A visit window of ±2 days is allowed for all visits starting at Visit 3. The visit window of ±2 days is relative to the first dosing visit date.  
e  Data will be transferred from the Screening or Baseline Visit, or Week 25 (Visit 27) of TP0003 or TP0006, as applicable. 
f  If urine pregnancy test is positive, a confirmatory serum pregnancy test is required. The study participant should not be dosed if pregnancy is confirmed. 
g  If required by site’s local procedure, the platelet count assessed by the local laboratory can be done -1 day for all visits. In exceptional cases for site dosing 
visits without a current platelet count, the last two platelet counts can be considered, provided the platelet counts were stable during the last two dosing visits 
(between 50 to 150×109/L and no dose change) and that the dose administered during the last two dosing visits was not changed and is not planned to be 
changed at the current dosing visit. Study participants should not have experienced any ITP signs and symptoms or AEs since the last dosing visit. 
h  If study participants rolled over from TP0003 or TP0006 using the +3 day window, then a new platelet count is needed prior to IMP dosing. 
i  Platelet counts can be taken at the indicated home visits; home visit are allowed if the previous 4 platelet counts were stable between 50 to 150×109/L and there 
was no dose change. If criteria are met, the visit may be conducted at home, administering the same dose of IMP as for the previous visit. 
j  The ECG should be performed prior to blood collection for assessment of laboratory parameters. The ECGs have to be performed pre-dose and 4 hours post-
dose at Day 1, and only pre-dose at Day 15, and Week 25. ECGs should also be performed at the EOS Visit (Week 60). 
k  Local reading for inclusion of study participants by qualified personnel is sufficient. 
l  Vital signs will include BP, pulse rate, and body temperature. On the dosing days, for the first 2 weeks (W1, W2), vital signs will be measured prior to IMP 
administration, at the end of the infusion, and 4 hours after the end of the infusion. For the next 3 visits (W3, W4, W5) vital signs will be measured prior to 
IMP administration, at the end of infusion, and 1 hour after the end of infusion. From W6, vital signs will be measured prior to IMP administration, at the end 
of the infusion, and 15 minutes after the end of infusion. At nondosing visits, vital signs need only to be taken once during the visit. In case of dose increase, 
vital signs will be measured prior to IMP administration, at the end of infusion and 1 hour after the end of infusion for the next 2 infusions. In case of an 
untoward event, additional vital signs (unscheduled assessment) should be taken at the discretion of the investigator and post-observation time can be extended. 
These recommendations are also applicable for dosing at site and at home. 
m  Samples for total cholesterol, LDL, HDL, and triglycerides will be collected at Weeks 13 and 25 only.  
n  For study participants who received COVID vaccine prior to entry into TP0004. 
o  For study participants who received COVID vaccine during enrollment into TP0004. The collection of COVID-19 Baseline samples should occur 2 to 3 weeks 
after the participant has received his/her last vaccination (ie, second dose of a 2-dose vaccine, or a booster vaccination). A second sample should be collected 3 
months after last vaccination and a third sample should be collected 6 months after last vaccination. 
p  The TB signs and symptoms questionnaire have to be performed every 12 weeks (90 days) starting with Week 13 and in Weeks 25, 37, 49, and at the EOS 
Visit (Week 60). 
q  Prior to dosing, management of infections and hypogammaglobulinemia must be considered as per Appendix 22, Section 10.22. 
r  On dosing days, for the first 2 weeks, a 4-hour post-dose observation will be in place. Assuming the first 2 doses were well tolerated, on dosing days in Week 
3, 4, and 5, a 1-hour post dose observation will be in place. Assuming the first 5 doses were well tolerated, on subsequent weeks, a 15-minute post-dose 
observation will be in place. However, if the dose needs to be decreased due to a TEAE(s) or dose needs to be increased, post dose observation will be extended 
to 1 hour after the end of infusion for the next 2 infusions. The post-dose observation time frame may be extended at the discretion of the investigator. These 
recommendations are applicable for dosing at site and at home. Approval from the investigator and sponsor is required prior to the start of home dosing. 
s  Unless specified, samples are collected predose when the IMP is administered at the same visit. 
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t  Serum complements (C3, C4) and plasma complements (C3a, C5a) should be taken predose at Baseline (Day 1) and at Week 33 for all study participants. 
Additional samples should be collected 2 hours and 4 hours postevent or as soon as possible before the next IMP for study participants with infusion reaction or 
hypersensitivity reaction (see Section 8.2.8). 
u  Optional blood collection if study participant ticks “yes” on the pharmacogenomics substudy ICF. 
v  Exploratory biomarker samples should be taken predose at Baseline (Day 1) and predose at Week 33. Additional samples should be collected 4 hours postevent 
or as soon as possible before the next IMP for study participants with severe and/or serious headaches or severe and/or serious GI disorders (ie, abdominal pain, 
diarrhea, vomiting; see Section 8.2.8). 
w  If total IgG levels are <1g/L, ad hoc assessments (eg, additional IgG samples) may be performed to monitor recovery of IgG levels. See Section 10.22. 
x  PROs to be completed prior to IMP dose and prior to any other study procedures. 
y   For study participants who self-infuse, to be completed once, prior to first self-infusion. 
z   To be completed within 1 hour after the first and second consecutive self-infusion. 
aa  This assessment is applicable only to participants experiencing moderate, severe and/or serious headache (see Section 10.20), and will be performed daily until 
resolution (ie, if headache becomes mild, normal collection of AEs should apply). This assessment can also be done remotely eg, via phone interview. 
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2 
INTRODUCTION 
Rozanolixizumab (UCB7665) is a humanized IgG4P monoclonal antibody that is being 
developed as an inhibitor of the activity of the FcRn for IgG. 
By blocking the IgG binding site of FcRn, rozanolixizumab accelerates the catabolism of IgG 
antibodies, including IgG autoantibodies. The aim is to reduce the concentration of pathogenic 
IgG in patients with autoimmune diseases mediated by the action of IgG autoantibodies. 
The FcRn recycles IgG and albumin and transports it bidirectionally across epithelial barriers. 
Recent studies have shown that FcRn rescues both IgG and albumin from intracellular lysosomal 
degradation by recycling it from the sorting endosome to the cell surface (Roopenian and 
Akilesh, 2007). Neonatal Fc receptor may also mediate transcytosis of IgG to facilitate its 
distribution within tissues. Rozanolixizumab has been specifically designed to block IgG binding 
to FcRn without blocking the binding and recycling of albumin. 
Rozanolixizumab binds with high affinity to FcRn at both neutral and acidic pH. 
Immunoglobulin G that is constitutively taken up by pinocytosis into cells fails to bind to FcRn, 
even at the acidic pH found in the endosome. It is therefore not recycled and is trafficked to the 
lysosomes for degradation. 
Production of pathogenic IgG autoantibodies is the major pathophysiology leading to a number 
of autoimmune diseases, which include ITP, myasthenia gravis (MG), pemphigus vulgaris, 
Goodpasture’s syndrome, neuromyelitis optica, Guillain-Barré syndrome, and chronic 
inflammatory demyelinating polyradiculoneuropathy. 
As individual disease entities, IgG autoantibody-mediated conditions are relatively rare. 
Treatment of these disorders remains a difficult clinical problem, requiring in many of these 
conditions the long-term use of corticosteroids alone or combined with other immunomodulatory 
agents. These therapeutic approaches are not effective in all patients and conditions and have 
broad immunosuppressive effects causing considerable toxicity and treatment-related morbidity. 
Treatments aimed at reducing the quantity of circulating IgG autoantibodies, including 
plasmapheresis, immunoadsorption, or high dose intravenous IVIg, are being used for primary 
and secondary therapy of autoimmune diseases. The therapeutic approach of these treatments is 
thought in part to be based on lowering levels of pathogenic autoantibodies, which represents 
rational and effective treatment modalities of autoimmune diseases. 
Therefore, specific and sustained removal of the IgG autoantibodies by FcRn blockade may 
provide an effective therapeutic option for IgG autoantibody-mediated autoimmune disorders. 
More detailed information regarding the nonclinical and clinical development programs for 
rozanolixizumab, including all completed and ongoing studies, can be found in the Investigator’s 
Brochure (IB). 
2.1 
Study rationale 
Immune thrombocytopenia, previously defined as immune thrombocytopenic purpura and 
idiopathic thrombocytopenic purpura (Rodeghiero et al, 2009), is a rare, orphan, hematological 
autoimmune disease characterized by an isolated low platelet count (thrombocytopenia) caused 
by specific antibodies directed against platelets and the absence of other causes of 
thrombocytopenia. In a pathological disease state these platelets are coated with autoantibodies 
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to platelet membrane antigens, resulting in splenic sequestration and phagocytosis by 
mononuclear macrophages. The resulting shortened life span of platelets in the circulation, 
together with platelet underproduction by autoantibody-mediated megakaryocytes inhibition 
results in a decreased platelet count (Arnold et al, 2015; McMillan et al, 2004). 
The spleen is the key organ in the pathophysiology of ITP, as it is the site of autoantibody 
production (white pulp) and the site of phagocytosis of autoantibody-coated platelets (red pulp). 
The slow passage of platelets through splenic sinusoids with a high local concentration of 
antibodies, and Fc-gamma receptors on splenic macrophages supports the role of the spleen as a 
site of platelet destruction (Sandler, 2000). 
The major goal for treatment of ITP is to achieve a platelet count that prevents major bleeding 
rather than correcting the platelet count to normal levels. The management of ITP should be 
tailored to the individual patient and it is rarely indicated in those with platelet counts >50×109/L 
in the absence of bleeding, trauma, surgery, or high-risk factors (eg, patients on anticoagulation 
therapy) (EMA/CHMP/153191/2013, 2014). However, there is general agreement that adults 
with a count of <30×109/L with bleeding at diagnosis require treatment. 
The first line of treatment for newly-diagnosed ITP is generally agreed and is based on the use of 
corticosteroids and IVIg. Although corticosteroids are effective, their long-term use is not 
recommended due to concerns over their safety (eg, osteoporosis, hypertension, 
immunosuppression). Patients who fail to respond or who relapse face the options of treatment 
with second line drug therapy or splenectomy, but there is no clear evidence to support the best 
approach (Rodeghiero et al, 2009; Provan et al, 2010; Neunert et al, 2011). Splenectomy can 
provide long-term efficacy in approximately 60% of cases, and recent guidelines suggest 
considering a splenectomy after 12 months. Splenectomy is an invasive procedure associated 
with acute complications (due to thrombocytopenia-like bleeding events) and long-term 
complications from loss of splenic functions. Asplenic individuals are at an increased risk of life-
threatening infections, although minimized with vaccination prophylaxis. Splenectomy may 
increase morbidity from venous thromboembolism or atherosclerosis (Ghanima et al, 2012). 
Second‑line drug therapies include high-dose dexamethasone or methylprednisolone; high-dose 
IVIg or anti-Rho (D) Ig; vinca alkaloids; dapsone and danazol; the immunosuppressants 
cyclophosphamide, azathioprine, and cyclosporine; or mycophenolate mofetil and Helicobacter 
pylori eradication, if applicable. The anti-CD20 monoclonal antibody rituximab, even if not 
licensed for the treatment of ITP, and the thrombopoietin-receptor agonists (eltrombopag, 
romiplostim [both approved in the US and Europe] and avatrombopag [approved in the US in 
2019]) are considered as second-line (Ghanima et al, 2018) as well as third-line options. In 2018, 
in the US, fostamatinib, a spleen tyrosine kinase-inhibitor, was been approved for the treatment 
of chronic ITP. Each of these treatments discussed above, has unique benefits, limitations, 
tolerability considerations, and risks. Taking the side-effect profile and long‑term complications 
of existing treatments together, there remains a considerable unmet medical need for novel 
therapeutic options in the treatment of persistent and or chronic ITP. 
By blocking the activity of FcRn, rozanolixizumab accelerates the catabolism of antibodies and 
reduces the concentration of pathogenic IgG in primary ITP patients, thus potentially offering a 
well-tolerated, effective, and convenient alternative to existing treatments. This Phase 3 OLE 
study will evaluate the longer-term safety and tolerability of rozanolixizumab with repeat dosing 
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in study participants with primary ITP who have completed the parent studies TP0003 or 
TP0006.  
2.2 
Background 
To date, rozanolixizumab has been administered to human study participants in 9 clinical studies: 
UP0018, UP0060, CIDP01, CIDP04, MG0002, MG0003, MG0004, and its replacement study, 
MG0007, and TP0001. UP0018 is a completed first-in-human (FIH) study. MG0002 is a 
completed Phase 2a study in participants with generalized MG, TP0001 is a completed Phase 2 
study in study participants with primary ITP and CIPD01 is a completed Phase 2a study in study 
participants with CIDP. UP0060 is a Phase 1 study in healthy volunteers, CIDP04 (OLE) is an 
ongoing Phase 2a study in study participants with CIDP, and MG0003 and MG0004 (OLE 
replaced by MG0007) are ongoing Phase 3 studies in study participants with generalized MG. 
CIDP01 is a completed Phase 2a, multicenter, randomized, participant-blind, investigator-blind, 
placebo-controlled, parallel-group study with the primary objective of evaluating the clinical 
efficacy of rozanolixizumab as a treatment for study participants with CIDP. There were 2 
treatment arms in this study:  
• Treatment Arm 1: rozanolixizumab 10mg/kg sc (12 doses administered at 12 weekly visits) 
• Treatment Arm 2: placebo sc (12 doses administered at 12 weekly visits) 
Overall, weekly administration of rozanolixizumab at a dose level of 10mg/kg SC was generally 
well tolerated, with an acceptable safety profile. No new safety concerns were identified. The 
incidence of TEAEs was similar between the rozanolixizumab and placebo groups, with the 
exception of the TEAE of injection/infusion site reactions which was reported at a higher 
frequency in study participants treated with rozanolixizumab. The majority of TEAEs were of 
mild to moderate intensity. The only severe TEAEs reported were in the context of underlying 
CIDP. During the Treatment Period, 10 (58.8%) study participants in the rozanolixizumab group 
and 5 (29.4%) in the placebo group experienced at least 1 drug-related TEAE. During the 
Observation Period, 1 (5.9%) study participant each in the rozanolixizumab and placebo groups 
experienced at least 1 drug-related TEAE. Two (11.8%) study participants in the 
rozanolixizumab group experienced serious TEAEs of CIDP relapse which were in the context 
of their underlying CIDP. No cases of severe headache, moderate or severe abdominal pain, 
moderate or severe vomiting, or severe diarrhea were reported. One (5.9%) study participant 
each in the rozanolixizumab and placebo groups experienced moderate diarrhea. No clinically 
meaningful trends were observed for clinical laboratory evaluations, vital signs measurements, or 
physical examinations.  
CIDP04 is an ongoing Phase 2a, multicenter, open-label extension study to investigate the long-
term safety, tolerability, and efficacy of rozanolixizumab in subjects with CIDP. The study 
includes 2 Treatment periods with 10mg/kg doses of rozanolixizumab by sc infusion at weekly 
intervals in two parts of the study (Treatment Period Part 1: 24 weeks, Treatment Period Part 2: 
52 weeks). 
TP0001 is a completed, Phase 2, multicenter, open-label, multiple-arm study to evaluate the 
safety and tolerability of rozanolixizumab in study participants with primary persistent and 
chronic ITP. The following dose arms were used in the study: 
• Dose Arm 1 (15 participants): rozanolixizumab 4mg/kg sc (5 doses at 1-week intervals) 
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• Dose Arm 2 (15 participants): rozanolixizumab 7mg/kg sc (3 doses at 1-week intervals) 
• Dose Arm 3 (12 participants): rozanolixizumab 10mg/kg sc (2 doses at 1-week intervals) 
• Dose Arm 4 (12 participants): rozanolixizumab 15mg/kg sc (1 dose) 
• Dose Arm 5 (12 participants): rozanolixizumab 20mg/kg sc (1 dose) 
 
 
Data from TP0001 indicate that rozanolixizumab was tolerated with an acceptable safety profile 
after multiple doses (4mg/kg, 7mg/kg, and 10mg/kg) and single doses (15mg/kg and 20mg/kg). 
The most frequent adverse event (AE) was headache (mild to moderate in intensity) and no 
severe headache was reported. There were no TEAEs leading to IMP discontinuation. 
Four serious TEAEs were reported overall (none were considered to be treatment-related by the 
investigator and were related to the underlying disease). A dose-dependent decrease in total IgG 
was observed: 43.6% (range 21.9% to 68.6%) for the 4mg/kg group (~Day 29), 49.9% (range 
29.5% to 65.5%) for the 7mg/kg group (~Day 22), 63.8% (range 38.4% to 75.0%) for the 
10mg/kg group (~Day 15), and on Day 8, after a single dose, for the 15mg/kg and 20mg/kg 
groups 52.3% (range 30.1% to 68.0%) and 60.2% (range 51.8% to 65.4%), respectively. 
Responders were classified as having a clinically relevant platelet response (≥50×109/L). Five 
(35.7%) participants in the 4mg/kg and 7mg/kg groups, 5 (45.5%) of 11 participants in the 
10mg/kg group, 8 (66.7%) of 12 participants in the single administration 15mg/kg dose group, 
and 6 (54.5%) of 12 participants in the single administration 20mg/kg group were clinically 
relevant responders. 
Based on the above, UCB considered that TP0001 established supportive evidence of efficacy 
and safety, and proceeded with the development of rozanolixizumab for the treatment of adults 
with persistent or chronic primary ITP in two pivotal phase 3 studies prior to the start of this 
study, TP0004. 
TP0003 and TP0006 are Phase 3, multicenter, randomized, double-blind, placebo-controlled 
studies evaluating the efficacy, safety, and tolerability of rozanolixizumab initially administered 
as a single fixed dose equivalent to 
 sc infusion followed by repeated bi-weekly fixed 
doses of approximately
 sc infusion in adult study participants with primary ITP. In 
protocol amendment 3, the starting fixed dose equivalent to 
sc was removed due to the 
change to 
 weekly dosing.  
The current OLE study, TP0004, is a study that will assess the long-term safety, tolerability, and 
efficacy of rozanolixizumab in all study participants completing the 24-week Treatment Period 
in TP0003 or TP0006 (irrespective of rescue medication) and fulfilling the eligibility criteria for 
TP0004. 
2.3 
Benefit/risk assessment 
Although there were a number of treatment options approved for chronic ITP in recent years, 
there is still an unmet medical need as, for many of these medications, the effect diminishes over 
time. The current available therapies like thrombopoietin-receptor agonists (TPO-RAs) have 
dietary exclusions, require liver function test monitoring, or increase the risk of thrombosis or 
thromboembolic events. Corticosteroids are associated with significant long-term side effects. 
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Thus, there is an unmet medical need for new treatments that can reduce the burden of existing 
therapies to patients, both for chronic and intermittent treatment. 
The clinical efficacy data obtained in the Phase 2 study, TP0001, indicate that rozanolixizumab 
has a rapid effect on lowering IgG and rapid onset of platelet response (increase in platelet count 
>50×109/L) and an acceptable safety profile. The ability to administer via sc infusion results in 
low systemic fluid volumes with no impact on plasma viscosity, significant reduction in time for 
infusion, and reduced potential for infusion reactions.  
The clinical safety data to date indicate that rozanolixizumab is well tolerated, and the common 
side effects are generally mild to moderate in severity, can be monitored and are manageable. 
The most common adverse drug reactions observed after use of rozanolixizumab across 
indications are headache, and GI disturbances (diarrhea, nausea, vomiting). Potential risks 
include serious infusion/hypersensitivity reactions, serious infections, and effects on vaccination 
response. These risks of serious infusion/hypersensitivity and serious infections can be mitigated 
by careful monitoring, exclusion of at-risk study participants, and appropriate protocol 
withdrawal and stopping criteria. Additionally, protocol guidance for management of GI 
disturbances, severe headaches, and infection is also provided as well as expedited reporting 
requirements of AESM. 
As with any other monoclonal antibody therapy, the treatment with rozanolixizumab could be 
associated with the development of ADA against rozanolixizumab.  
Participants will be closely monitored for acute infusion reactions or hypersensitivity reactions in 
TP0004. In the event of a recorded infusion reaction or hypersensitivity reaction, further 
complements analyses will be performed alongside the planned ADA assessment to assist in 
immune complex disease determination. The 52-week treatment duration of TP0004 is regarded 
as adequate to assess the risk of immunogenicity after 
 treatment administration. 
Restrictions on use of live vaccines have been defined in the exclusion criterion #14. If 
vaccination with non-live vaccines (including COVID-19 vaccines) is considered necessary once 
a study participant has started therapy with IMP, the degree of protection afforded with a vaccine 
may be compromised while the participant is being treated with IMP. 
Based on its mechanism of action, rozanolixizumab will reduce total IgG levels including 
vaccine specific IgG. However, it is unlikely that the immunogenicity of the vaccine will be 
compromised by FcRn inhibition. Given the study population characteristics (eg, status of the 
underlying disease, concomitant immunosuppressive therapies, etc) it is recommended to 
perform individualized benefit risk assessment for vaccination and specifically vaccination 
against COVID-19 infection. If COVID-19 vaccination is planned, information regarding 
vaccine should be recorded (Section 6.4.1). COVID-19 vaccination should be scheduled, if at all 
possible, to allow differentiation of safety profiles of IMP and vaccine (eg, a minimum window 
of 72 hours between COVID-19 vaccination and IMP administration). If any AEs were to occur, 
they should be handled as described in (Section 8.2.9) with causality assessment provided for 
both IMP and vaccine. Additionally, to further characterize the effect of rozanolixizumab on 
COVID-19 vaccination response, measurement of vaccine titers are being tested in our 
development programs. 
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More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of TP0004 may be found in the current version of the IB.
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3 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
• To assess the long-term safety and 
tolerability of treatment with 
rozanolixizumab 
The primary safety endpoints are: 
• Occurrence of treatment-emergent adverse 
events (TEAEs) 
• Occurrence of TEAEs leading to permanent 
withdrawal of rozanolixizumab (ie, study 
discontinuation) 
The other safety endpoints are: 
• Occurrence of treatment-emergent adverse 
events of special monitoring (AESM) 
• Occurrence of serious TEAEs 
• Occurrence of treatment-related TEAEs 
• Vital sign change from Baselinea (blood 
pressure [BP], body temperature, and pulse 
rate) at each scheduled assessment during 
Treatment and Safety Follow-Up (SFU) 
Periods 
• 12-lead electrocardiogram (ECG) change from 
Baselinea at each scheduled ECG assessment 
visit 
• Laboratory change from Baselinea 
(hematology, including coagulation parameters, 
clinical chemistry, and urinalysis) at each 
scheduled assessment during Treatment and 
SFU Periods 
• Changes from Baselinea in concentrations of 
total protein and albumin 
• Changes from Baselinea in serum (C3 and C4) 
and plasma (C3a and C5a) complement levels 
at each scheduled assessment during study (for 
study participants experiencing infusion or 
hypersensitivity reactions) 
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Objectives 
Endpoints 
Secondary 
• To assess the long-term clinical 
efficacy of treatment with 
rozanolixizumab 
The secondary efficacy endpoint is: 
• Stable Clinically Meaningful Response, defined 
as Clinically Meaningful Response (ie, platelet 
count ≥50×109/L) without rescue therapy at 
≥70% of the visits over the planned 52 week 
Treatment Period starting at Week 4 
The other efficacy endpoints are: 
• Stable Response defined as platelet count 
≥30×109/L and absence of bleedingb without 
rescue therapy at ≥70% of the visits over the 
planned 52-week Treatment Period starting at 
Week 4  
• Cumulative number of weeks with Clinically 
Meaningful Response over the 52-week 
Treatment Period 
• Cumulative number of weeks with platelet 
counts ≥30×109/L over the planned 52-week 
Treatment Period 
• Duration of first Clinically Meaningful 
Response starting at Week 4 
• Mean Change from Baselinea in platelet count 
at each visit 
• Use of rescue medication by visit 
• ITP specific Bleeding Assessment Tool (ITP-
BAT) bleeding events and severity by visit  
• To assess the effect of 
rozanolixizumab on study participant 
perceived symptoms 
• Change from Baselinea to Week 53 including 
all intermediate timepoints for ITP-PAQ 
Symptoms domain score 
• To assess the reduction in use of 
steroids and other concomitant ITP 
medications  
• AUC of the oral steroid dose over time 
• Change in dose and/or frequency of 
concomitant ITP medications (excluding 
corticosteroids) over time  
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Objectives 
Endpoints 
Exploratory 
• To assess the effect of 
rozanolixizumab on patient-reported 
outcomes (PROs) 
• Change from Baselinea in FATIGUE-PRO 
Physical Fatigue Score  
• Change from Baselinea in Patient Global 
Impression of Severity (PGI-S)  
• Patient Global Impression of Change (PGI-C) 
at all available post-Baselinea assessments  
• Change from Baselinea in ITP-Patient 
Assessment Questionnaire (ITP-PAQ) domain 
scores  
• To assess the clinical efficacy of 
rozanolixizumab in study 
participants with first exposure to 
rozanolixizumab 
• In study participants with first exposure to 
rozanolixizumab: Durable Clinically 
Meaningful Platelet Response of ≥50×109/L, 
for at least 4 of 6 
 visits between 
Weeks 13 to 25 of the study 
• In study participants with first exposure to 
rozanolixizumab: Time to first Clinically 
Meaningful Platelet Response of ≥50×109/L: 
time from starting treatment to achievement of 
first response of ≥50×109/L 
• To assess effect of rozanolixizumab 
on health-related quality of life 
(HRQoL) and broader disease 
impact 
• Change from Baselinea in European Quality of 
Life (EuroQol)-5 dimension 5 Levels 
Assessment (EQ-5D-5L) item responses 
• Change from Baselinea in Short-Form 36-Item 
(SF-36) domain and composite scores 
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Objectives 
Endpoints 
• To assess resource utilization 
• Number and length of hospitalizations 
• Number of infusion center admissions 
• To assess the experience with the 
subcutaneous (sc) self-administration 
• PRE-Self Injection Assessment Questionnaire 
(SIAQ) (Infusion version) domains scores 
before the first sc self-administration in 
participants that self-administer 
• POST-SIAQ (Infusion version) domains scores 
at each available visit in participants that self-
administer 
• To assess the PD effect of 
rozanolixizumab 
• Total serum IgG (absolute value) and change 
from Baselinea (absolute value and percentage) 
in serum IgG and in serum IgG subclass 
concentration at each scheduled assessment 
• Absolute value and change from Baselinea 
(absolute value and percentage) in serum Ig 
concentrations (IgA, IgE, IgM) at each 
scheduled assessment 
• To evaluate the incidence and 
emergence of antidrug antibody 
(ADA) of rozanolixizumab 
• ADA at each scheduled assessment 
• To assess the pharmacokinetics (PK) 
of rozanolixizumab administered by 
sc infusion 
• Plasma concentrations of rozanolixizumab at 
each scheduled assessment  
• To evaluate clinical response 
following end of dosing  
• Platelet count by visit after end of dosing 
• Time from end of rozanolixizumab dosing to 
loss of clinically relevant response 
• To assess the influence of 
rozanolixizumab treatment on 
vaccination titers 
• Percent change from Baselinea in vaccination 
titers against Streptococcus pneumoniae, 
Neisseria meningitidis, and Haemophilus 
influenzae in splenectomized study participants  
• To assess the effect of 
rozanolixizumab on post-vaccination 
biomarker(s) in study participants 
who received the COVID-19 vaccine 
• Change in post-vaccination biomarker(s) over 
time in study participants who received the 
COVID-19 vaccine  
a Baseline definitions  will be detailed in the SAP. 
bAbsence of bleeding indicated by Grade 0 for all domains of the Skin-Visible Mucosa-Internal Organs (SMOG) 
tool, or a Skin Grade of 0 or 1. 
 
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4 
STUDY DESIGN 
4.1 
Overall design 
This is a Phase 3, multicenter, 1-year OLE study of TP0003 and TP0006 parent studies with 
rozanolixizumab in study participants with persistent or chronic primary ITP.  
Study participants from TP0003 or TP0006 who have completed the 24-week Treatment Period 
(irrespective of rescue therapy) and meet eligibility criteria for TP0004 will be offered 
enrollment. Splenectomized participants rolling over from parent studies will have a vaccination 
titer for Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis (N. meningitidis), 
and Haemophilus influenzae (H. influenzae) collected per Schedule of Activities (Section 1.3). In 
addition, splenectomized participants should continue to carry a splenectomy card and a 
recommended antibiotic (if applicable per local guidance).  
All study participants rolling over into TP0004 will receive rozanolixizumab at the assigned dose 
level from Week 25 in the parent studies if the platelet count was between ≥50×109/L and 
≤150×109/L. If outside of this range, a higher or lower dose level than the final sc infusion in 
TP0003 or TP0006 is permitted according to Table 4-2 and Figure 4-1.   
During the first two dosing visits, all study participants will stay for 4 hours after the end of 
infusion for observation at the site. Assuming the first 2 doses were well tolerated, the 
observation time will be 1 hour after the end of infusion for another 3 infusions. Assuming the 
first 5 doses were well tolerated, on subsequent weeks, a 15-minute post-dose observation will be 
in place for the remaining visits until Week 52. If needed, observation time can be extended for 
each study participant. However, if the dose needs to be decreased due to a treatment-emergent 
adverse event(s) (TEAE[s]) or dose needs to be increased, the post-infusion observation period 
will be changed to 1 hour for the next 2 infusions. The post-dose observation time frame may be 
extended at the discretion of the investigator.  
This study will assess whether continued 
dosing with rozanolixizumab is well tolerated with 
an acceptable safety profile. This study will also assess whether continued rozanolixizumab sc 
infusions 
 over a period of 52 weeks will maintain a durable Clinically Meaningful Platelet 
count of ≥50×109/L. Starting at Week 2 and until Week 13, platelet counts will be measured 
every week at a local laboratory and every 2 weeks starting at Week 15. Site visits will occur 
every week starting at Week 2. If applicable, home visits and home dosing are permitted per the 
Schedule of Activities (Section 1.3). 
In exceptional circumstances (eg, pandemic, hurricanes, etc) where study-specific investigations 
may not be conducted according to study protocol, contingency measures will be in place (see 
Section 8). If enrollment into TP0004 is not possible at the time of Week 25 (+3 days) in 
TP0003/TP0006, the SFU assessments should be conducted. Once the circumstances during or 
after the pandemic allow, these study participants may be allowed to continue in the OLE study 
in consultation with the UCB study physician. 
The total maximum study duration per study participant is up to 59 weeks, including a Treatment 
Period (52 weeks) and a SFU Period (8 weeks after final dose). The eligibility to participate in 
the study will be determined at the Baseline Visit (Day 1). Participants will receive a dose of 
rozanolixizumab 
 through Week 52. After the final dose in TP0004, participants will be 
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followed in an 8-week SFU Period. The End of Study (EOS) visit will be performed after the 
SFU Period. 
Fixed dose equivalents across body weight tiers will be employed in this study according to 
Table 4-1. 
Table 4-1: 
TP0004 dose levels and weight tiers of IMP 
Dose eqv 
 
Bodyweight 
 
Dose level 1 
 
Dose level 2 
 
Dose level 3 
>35 to <50kg 
 
 
No weight adjustment    
 
≥50 to <70kg 
 
 
≥70 to <100kg 
 
 
≥100kg 
 
 
eqv=equivalent 
In the case of a study participant of the lowest body weight tier (below 50kg) and in the lowest dose level with a 
platelet count between >150×109/L and <400×109/L, the investigator might decide to temporarily stop treatment 
according to medical judgment based on the observation of platelet variability. Otherwise the treatment must be 
stopped if platelets increase to above 400×109/L. 
An external IDMC will be utilized to review the safety data at predefined intervals and ad hoc as 
needed should any emerging safety concern arise during the study. The IDMC will review 
implications of individual and cumulative cases to continuance of the study in an ongoing 
fashion. Key safety data may be pooled at the discretion of the IDMC for protection of all study 
participants, if warranted. 
Based on feedback from the IDMC, 
 dosing was implemented in protocol amendment 2. 
Study participants being treated with the 
 dosing regimen will switch to the 
 
dosing regimen once protocol amendment 2 is approved at the respective study site.  
At Baseline (Day 1), which corresponds to Week 25 (Visit 27) of the parent studies, TP0003 or 
TP0006, all study participants (whether randomized to placebo or rozanolixizumab in the parent 
studies) will enter TP0004 and receive rozanolixizumab treatment 
 at the assigned dose level 
at the end of TP0003 or TP0006, if the platelet count was between ≥50×109/L and ≤150×109/L. 
Study participants previously randomized to placebo will also enter the study at the assigned 
dose level at the end of the parent studies. Doses can be adjusted if platelets are outside the 
specified range, as per dose adjustment in Table 4-2. After Baseline, the next administration of 
rozanolixizumab will be on Week 2 (Visit 3) and 
 thereafter, as an sc infusion to maintain 
platelet count ≥50×109/L. 
Rozanolixizumab dose levels based on body weight tiers being explored in TP0004 are as 
follows: 
• Equivalent to 
 
• Equivalent to
 
• Equivalent to approximately 
 (
 total dose) 
 
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If platelet counts are >150×109/L or <50×109/L on 2 consecutive visits, the dose should be 
adjusted for safety reasons (ie, high platelet count or AE) or efficacy reasons as specified in 
Table 4-2 and Table 4-1. The same dose regimen should be maintained if possible throughout the 
study. 
Table 4-2: 
Dose adjustments of rozanolixizumab 
Platelet count resulta  
Dose adjustment (based on weekly platelet counts) 
<10×109/L  
Increase by one dose level, unless study participant is on 
maintenance dose of 
Additional rescue therapy is 
highly recommended as per Section 6.4.3  
≥10×109/L to <30×109/L (on at least two 
consecutive visits) 
Increase by one dose level, unless study participant is on 
maintenance dose of 
 Additional rescue therapy is 
recommended as per Section 6.4.3  
≥30×109/L to <50×109/L 
(on at least two consecutive visits) 
Increase by one dose level, unless study participant is on 
maintenance dose of 
 
≥50×109/L to ≤150×109/Lb  
Continue with current dose level 
>150×109/L to <400 x109/L (on at least 
two consecutive visits) 
Decrease by one dose level, unless study participant is on 
maintenance dose of 
 
≥400×109/L 
Stop IMP treatment. 
Once the platelet count is ≤150×109/L, reinitiate treatment 
decreased by one dose level  
a  All analyses of platelet counts will be based on local laboratory results. 
b  Due to the interindividual variable platelet response in some study participants, platelet count may abruptly fall 
below 50×109/L after dose reduction or treatment discontinuation. In these cases, if clinically appropriate, higher 
cut-off levels of platelet count for dose reduction (>150×109/L) may be considered according to medical 
judgment, but should not exceed 250×109/L. 
For the dose adjustments where a decrease is required, study participants receiving 
 
should continue at this dose level, as dose reductions below 
 are not applicable. In the case 
of a study participant of the lowest body weight tier (below 50kg) and in the lowest dose level, 
with a platelet count between >150×109/L and <400×109/L, the investigator might decide to 
temporarily stop treatment according to medical judgment based on the observation of platelet 
variability. If platelet count increases to above 400×109/L then IMP must be stopped. 
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Figure 4-1: Dose adjustments of rozanolixizumab 
 
eqv=equivalent; 
 
* eqv: fix unit dose with body weight tiers equivalent to the mg/kg dose in terms of IgG reductions and safety 
profile. 
If treatment as per Table 4-2 and Figure 4-1 does not lead to an increase in platelet count 
≥30×109/L, the study participant can be treated with rescue therapy, if deemed needed by the 
investigator. If platelet counts are ≥10×109/L to <30×109/L or active bleeding, rescue therapy is 
recommended (eg, commercially available medication, such as intravenous immunoglobulin 
(IVIg), high dose corticosteroids and pulse steroids, platelet transfusions, or any other 
medication listed in Section 6.4.3). If platelet counts are <10×109/L, rescue therapy is highly 
recommended as per Section 6.4.3. If a study participant has been down-titrated to a fixed-unit 
dose equivalent to 
 or the 
total dose (corresponding to an average 
dose in 
a participant weighing 70kg), and platelet count decreases to <50×109/L, then up-titration to a 
fixed-unit dose equivalent to 
 or 
 respectively, would be allowed. 
Study participants will be treated for a maximum of approximately 52 weeks. After the final dose 
in TP0004, participants will be followed for safety follow-up purposes in an 8-week SFU Period. 
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4.2 
Scientific rationale for study design 
The target population for rozanolixizumab is patients with IgG autoantibody-mediated 
autoimmune disorders. TP0003 and TP0006, the parent studies of the current OLE study 
TP0004, are designed to assess whether multiple sc infusions of rozanolixizumab will result in a 
durable clinically meaningful platelet increase to count of ≥50×109/L in adult study participants 
with ITP. TP0004 plans to assess participants from TP0003 and TP0006 for up to a year and 
primarily evaluate the safety and tolerability of rozanolixizumab over a longer duration of 
treatment. 
The possibility of chronic, regular, treatment with rozanolixizumab will be assessed in TP0004. 
Study participants who roll over from TP0003 or TP0006 will receive rozanolixizumab at the 
assigned dose level at the end of the parent studies as an sc infusion on Baseline (Day 1) which 
will be repeated on Week 2 (Visit 3), and then 
 thereafter. Study participants assigned to 
placebo through to Week 25 (in TP0003 or TP0006) will also receive rozanolixizumab at the 
assigned dose level at the end of the parent studies. As the study participants previously assigned 
to placebo in TP0003 and TP0006 are likely to have received rescue therapy in order to keep 
their platelet count >30×109/L, it is appropriate to start dosing with the previously assigned dose 
(equivalent to 
 or below). The platelet counts in all study participants are anticipated to 
be already above a critical level (>30×109/L) through previous therapy with rozanolixizumab 
itself or with rescue therapies. Thus, in order to maintain the blind of the pivotal studies, it is 
considered adequate to start with the final dose administered in TP0003 or TP0006. However. 
based on platelet counts, a higher or lower dose level is permitted. Dose levels being explored 
are equivalent to 
 and approximately 
 (
total dose) 
  
In case the enrollment into TP0004 is delayed, the rollover from TP0003 or TP0006 needs to be 
completed 3 days after the last visit, at the latest. In case of a late rollover, platelet counts will 
need to be remeasured. 
4.3 
Justification for dose 
Initially, a fixed-unit dosing regimen across body weight tiers equivalent to 
 (starting 
dose) followed by 
 (maintenance doses) 
 was proposed for use in the confirmatory 
TP0003 and TP0006 studies, based upon response rate (>50×109/L), time to onset of the platelet 
count increase, and safety profile observed in the Phase 2 study. Data from TP0001 showed that 
a 
 dose of 
 reached a 52% decrease in IgG from Baseline by Day 8, and a clinical 
response was observed for most study participants in the cohort before the IgG nadir on Day 8. 
The study also showed that the median (and range) of duration of platelet response (platelet 
count >50×109/L) following a dose of 
 and a 
 dose of 
 was 12 (6 
to 19) days and 11.96 (6 to 20) days, respectively. Hence, a starting dose of 
 equivalent 
followed by 
 equivalent 
 was expected to sustain IgG levels reduced from its 
Baseline level by >50% and expected to be sufficient to translate into a relevant platelet 
response. Dose adjustments to 
 or approximately 
 were allowed if medically 
indicated, eg, for thrombocytosis. The proposed dose regimens were stratified by weight tiers as 
presented in Table 4-1.  
Following the IDMC data review and the available OLE TP0004 data with the initially proposed 
dose regimen of
 the IgG reductions appear to be in concordance with the anticipated 
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reductions of ~50%, however the observed platelet count data do not seem to be sustained in 
TP0004 during the 
 dosing interval. Protocol Amendment 2 followed the advice from 
the external IDMC to increase the frequency of dosing, as in the OLE study (TP0004), platelet 
counts are not sustained over a 
dosing interval (observed platelet counts <50×109/L). 
Following the advice, the dose regimen for studies TP0003, TP0006 and OLE TP0004 will be 
changed to 
 equivalent 
This dose regimen is anticipated to be well tolerated, with 
an acceptable safety profile and more likely to sustain the platelet counts across the dosing 
interval reducing the risks associated with low platelet counts. A dose of 
 equivalent 
 is predicted to sustain IgG levels with mean percentage change from Baseline reduction of 
70% and maintain FcRn receptor occupancy (RO%) levels above 50% throughout the dosing 
interval as opposed to the 
 that only sustained it above this level during the first week 
following each dose and not for the entire
 period between doses.  
A 
 equivalent 
 dose regimen is anticipated to achieve RO% from peak to trough in a 
range of 99 to 50% during the 
 dosing interval and predicted to achieve mean 
concentrations at steady state (Cmax,ss) of ~30μg/mL (2 days post dose) and Ctrough of 0.31μg/mL. 
In terms of safety, 2x10mg/kg weekly doses have been tested in TP0001 and showed a good 
safety and tolerability profile. In addition, this dose regimen of 10mg/kg of rozanolixizumab QW 
has been studied in other indications like CIDP01, where 34 study participants (1:1 
placebo:rozanolixizumab) followed 12 weekly doses of 10mg/kg administrations, from which at 
least 6 study participants enrolled in the follow up study CIDP04 with a total of 52 weeks 
10mg/kg QW doses. This dose regimen was generally well tolerated, with an acceptable safety 
profile, while no new safety concerns were identified. In addition, in order to avoid platelet count 
increases to ≥150×109/L, down-titration of the IMP dose level as described in Table 4-1 will be 
allowed. Weekly platelet assessments will be performed during the study, to support the dosing 
strategy and stabilize the dose regimen leading to platelet counts ≥50×109/L and minimize 
platelet counts ≥150×109/L in the participants. Up titration to fixed-unit doses of 
 
rozanolixizumab equivalent 
will also be allowed to maintain stable platelet counts of 
>50×109/L over the Treatment Period if a previous down titration has occurred and subsequently 
platelet counts dropped again to below 50×109/L. 
In summary, the new proposed dose regimen for the Phase 3 studies is a 
 equivalent 
dose on a 
basis, allowing to downtitrate to 
 and 
 total dose based on the 
efficacy and safety profile. This regimen is supported by the observed data in the program thus 
far. 
4.4 
End of study definition 
A study participant is considered to have completed the study if he/she has completed all phases 
of the study including the SFU Period. Study participants will have an EOS Visit performed 
8 weeks after the final dose of IMP or the Early Withdrawal (EW) Visit. 
The EOS is defined as the date of the last visit of the last participant in the study. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
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5.1 
Inclusion criteria 
Study participants are eligible to be included in the study only if all of the following criteria 
apply: 
1b. Study participant completed TP0003 or TP0006 until Visit 27 (Week 25) and, in the opinion 
of the investigator, has been compliant with the TP0003 or TP0006 study assessments. 
2. The study participant is considered reliable and capable of adhering to the protocol, visit 
schedule, or medication intake according to the judgment of the investigator. 
Type of participant and disease characteristics: 
3. Criterion removed. 
4. Criterion removed. 
Sex 
5a. Study participants may be male or female:  
− A male participant must agree to use contraception as detailed in Appendix 4, 
Section 10.4 of this protocol during the Treatment Period and for at least 3 months after 
the final dose of study treatment and refrain from donating sperm during this period. 
− A female participant is eligible to participate if she is not pregnant (see Appendix 4, 
Section 10.4) as confirmed by a negative urine pregnancy test and not planning to get 
pregnant during the participation in the study, not breastfeeding, and at least one of the 
following conditions applies: 
◦ 
Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 
(Section 10.4). 
OR 
◦ 
A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 
(Section 10.4) during the Treatment Period and for at least 3 months after the final 
dose of study treatment. 
Informed consent 
6. Study participant is capable of giving signed informed consent as described in Appendix 1, 
Section 10.1.3 which includes compliance with the requirements and restrictions listed in the 
Informed Consent form (ICF) and in this protocol. 
5.2 
Exclusion criteria 
Participants are excluded from the study if any of the following criteria specific to TP0004 
apply: 
Medical conditions 
1. Study participant has any ongoing IMP-related SAE or ongoing severe IMP-related TEAE 
experienced during TP0003 or TP0006.  
2. Criterion removed. 
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3. Any withdrawal or permanent IMP discontinuation criteria from TP0003 or TP0006 met, a 
change in medical condition from TP0003 or TP0006, or significant bleeding requiring 
immediate treatment which, in the judgment of the investigator, precludes the participant 
from inclusion in TP0004 (eg, clinically significant bleeding, ongoing active or chronic 
infection, acute myocardial infarction, thromboembolic event, liver disease, high risk of GI 
bleeding, severe psychiatric condition). 
4. Late detection of an inclusion criterion not met for TP0003 or TP0006 if it affects the health 
status/safety of the study participant. 
5. Late detection of an exclusion criterion met for TP0003 or TP0006 that is related to ITP 
diagnosis or to the health status/safety of the study participant. 
Diagnostic assessments 
6b. Study participant has, at last available assessment of TP0003 or TP0006, 3.0x upper limit of 
normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), or alkaline phosphatase (ALP). 
− If study participant has >ULN for ALT, AST, or ALP that does not meet the exclusion 
limit at enrollment (last available assessment of TP0003 or TP0006), repeat the tests, if 
possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. 
− For study participants with a Baseline result >ULN for ALT, AST, ALP, or total 
bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful elevation 
must be recorded in the electronic Case Report form (eCRF). 
7a. Study participant has bilirubin >1.5xULN (unless confirmed Gilbert’s syndrome) at the last 
available assessment in TP0003/TP0006. If participant has elevations only in total bilirubin, 
fractionate bilirubin to identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin 
<35%). 
8. Female study participant who is pregnant or lactating. 
9a. Study participant has planned major elective surgical procedure for the duration of the study 
period. 
10a.Study participant has at the last available assessment in TP0003/TP0006, any laboratory 
abnormality that, in the opinion of the investigator, is clinically significant, has not resolved 
at Visit 1 (Day 1), and could jeopardize or compromise the study participant's ability to 
participate in this study. 
11a.Study participant has 12-lead ECG at Baseline with changes considered to be clinically 
significant upon medical review. The clinical significance of the findings needs to be 
assessed by the investigator to determine eligibility. 
12.Criterion removed. 
13. Study participant has at Baseline corrected QT interval for heart rate using Fridericia’s 
formula (QTcF) >450 msec (for male participants) or QTcF >470 msec (for female 
participants) or QTcF >480 msec in participants with bundle branch block. 
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14. Study participant has received a live vaccination within 8 weeks prior to Day 1 (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. 
For France-specific exclusion criteria (criterions #15, #16 and #17), see Appendix 7 
(Section 10.7). 
5.3 
Lifestyle restrictions 
There are no lifestyle restrictions during the study unless deemed to interfere with the 
compliance with the protocol as deemed by the investigator. 
6 
STUDY TREATMENTS 
Table 6-1: 
Treatments administered 
Study treatment name: 
Rozanolixizumab 
Dosage formulation: 
Solution for infusion 
Unit dose 
strength(s)/Dosage 
level(s): 
 
 
 
Fixed dose equivalent to 
 and approximately 
 based on body weight tiers.  
Route of 
administration: 
sc infusion 
Dosing instructions: 
Rozanolixizumab will be administered as a sc infusion with an 
 
 
 The study participant’s 
body weight at Baseline (TP0004 [re-measured] Baseline and Week 25) 
(refer to Section 9.2 for the definition of Baseline) will be used for the dose 
calculation. In the case of any blockage of the infusion, a suitable flush (eg, 
) is allowed. 
If the participant is unable to tolerate a
 a slower rate may be 
used at the discretion of the clinical personnel administering the infusion. 
Packaging and 
labeling: 
Rozanolixizumab will be provided in glass vials and will be labeled as 
required per country requirement. 
hr=hour; 
 sc=subcutaneous; w/v=weight/volume 
Details on the rate of infusion are provided in the IMP Handling Manual. 
6.1 
Preparation, handling, storage, and accountability requirements 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all IMP received and that any discrepancies were reported and 
resolved before the use of the IMP. 
Only participants enrolled in the study may receive IMP and only authorized site staff may 
supply or administer IMP. All IMPs must be stored in a secure, environmentally controlled, and 
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monitored (manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for IMP accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). 
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual. 
Further guidance and information for the final disposition of unused IMP are provided in the 
IMP Handling Manual. 
6.1.1 
Drug accountability 
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-participant 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. 
UCB 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 qualified person and/or 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 procedures 
(SOPs). Investigational medicinal product intended for the study cannot be used for any other 
purpose than that described in this protocol. 
6.2 
Measures to minimize bias: randomization 
An interactive response technology (IRT) will be used for assigning eligible participants to IMP 
based on a predetermined production randomization and/or packaging schedule provided by 
UCB (or designee). The randomization schedule will be produced by the IRT vendor. The IRT 
will generate individual assignments for kits of IMP, as appropriate, according to the visit 
schedule. 
The participant number assigned to study participants enrolled in TP0003 and TP0006 will be the 
same identifier used in TP0004. The participant number will be required in all communication 
between the investigator or designee and the IRT regarding a particular participant. Participant 
numbers and kit numbers will be tracked via the IRT. 
6.3 
Treatment compliance 
Drug accountability must be recorded on the Drug Accountability form (Section 6.1.1). 
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Details regarding treatment compliance are outlined in the Important Protocol Deviation 
Specification document. 
6.4 
Concomitant medications/treatments 
6.4.1 
Permitted concomitant treatments (medications and therapies) 
The concomitant medications and the highest dose permitted during the study are listed in 
Table 6-2. Dose tapering, especially for oral corticosteroids, is allowed. Any increase in 
concomitant ITP medication above Baseline (Visit 1, TP0004) dose is regarded as rescue 
therapy.  
For study participants who started rescue medication during TP0003/TP0006 and are still 
receiving rescue medication when rolling over to TP0004, Table 6-2 is applicable as soon as the 
respective rescue medication is stopped or the dose is decreased to less than or equal to the limit 
specified in Table 6-2. In such a situation, the rescue medication will not be considered as 
Baseline concomitant ITP medication and the rules for restarting IMP administration will apply, 
as per Section 6.4.3.  
If a study participant receives a COVID-19 vaccine, the product name and date of 
administration(s) should be captured in the eCRF as a concomitant medication. 
Table 6-2: 
Permitted concomitant treatments (medications and therapies) 
Permitted Medications 
Dose 
Oral Corticosteroids  
≤20mg/day (prednisone equivalent dose) 
Mycophenolate mofetil  
≤3g/day 
Cyclosporin 
≤5mg/kg/day for unmodified 
≤4mg/kg/day for modified 
Azathioprine 
≤3mg/kg/day 
Danazol 
≤15mg/kg/day 
Dapsone 
100mg/day 
Eltrombopag, Avatrombopag 
Any dose 
Fostamatinib 
Any dose 
The use of medicinal cannabidiols and medicinal marijuana (prescribed by a physician) is also 
permitted. For Japan-specific requirements, see Appendix 7, Section 10.7. 
6.4.2 
Prohibited concomitant treatments (medications and therapies) 
The following concomitant medications are prohibited during the study: 
• IVIg (unless it is given as rescue therapy) 
• All biologics including rituximab 
• Cyclophosphamide 
• Pimecrolimus  
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• Plasma exchange 
• Immunoadsorption 
• Anti-D 
• Any systemically administered corticosteroids above the allowed background dose (unless 
required as a rescue therapy) 
• Romiplostim 
• Vinca alkaloids (vincristine, vinblastine) 
• Anticoagulants and anti-platelets (eg, warfarin, heparin, clopidogrel, aspirin [enteric coated 
up to 150mg daily allowed], salicylics, dipyridamole, prasugrel, ticagrelor, tirofiban, 
abciximab) 
For study participants 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, such that a decision on the participant's continued participation in the study can 
be made. In an emergency situation, discussion should occur as soon as possible after the 
procedure. 
The use of prohibited concomitant treatment will lead to permanent discontinuation from IMP. 
Study participants should then complete the assessments outlined for the EW Visit and enter the 
SFU Period. 
6.4.3 
Rescue therapy 
Rescue therapy will be given per standard of care and at the discretion of the investigator. Any 
increase in concomitant ITP medication above Baseline (Visit 1, TP0004) dose is regarded as 
rescue therapy. Any systemically administered corticosteroids above the background doses (ie, 
pulse, oral and iv steroids) and any systemic corticosteroids used for the management of infusion 
reactions or other medical condition are also considered rescue therapy. Depending on the dose 
and/or type of rescue medication that is required a study participant may have to be discontinued 
as described in Section 6.4.3.1 and Section 6.4.3.2. 
6.4.3.1 
Rescue therapy not leading to discontinuation 
The following are defined as rescue therapies and can be administered without requiring study 
participants to be discontinued from the study (per investigator’s judgment): 
• Commercially available IVIg (once platelet count is <50×109/L, rozanolixizumab treatment 
can commence at the same dose as previously administered) 
• High dose corticosteroids (once platelet count is <50×109/L, rozanolixizumab treatment can 
commence at the same dose as previously administered)  
Note: A high dose of corticosteroids is defined as any iv administration of corticosteroids 
given for any reason or doubling of an oral dose resulting in a dose more than 20mg/day 
prednisolone equivalent dose. 
• An increase less than 25% from Baseline (Day 1 in TP0004), in permitted concomitant ITP 
therapies  
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• An increase less than 25% from Baseline (Day 1 in TP0004), in permitted concomitant 
immunosuppressants 
If such rescue therapy is given, the participant should continue in the study and complete all 
scheduled visits, as per the Schedule of Activities (Section 1.3). 
The date and time of rescue therapy administration as well as the name and dosage regimen of 
the rescue therapy must be recorded. 
Although the intervention of rescue therapy is allowable at any time during the study, the use of 
rescue therapy should be delayed, if possible, for at least 2 days following the administration of 
IMP to allow for the study treatment to have an effect. 
6.4.3.2 
Rescue therapy leading to discontinuation  
The following rescue therapies, if administered, will lead to permanent discontinuation of the 
study participant from the study: 
• Any increase in dose above 25% in a Baseline-permitted concomitant ITP therapy and 
immunosuppressants (Baseline, Day 1 in TP0004)  
• Initiation of oral steroids above 20mg/day 
• Platelet transfusion 
• Initiation of any additional ITP therapy (apart from IVIg and high dose corticosteroids) 
6.5 
Dose modification 
Dose modifications of the IMP are permitted in order to maintain the platelet counts between 
≥50×109/L and ≤150×109/L (Table 4-2 and Figure 4-1). 
Dose modifications or temporary discontinuation of the IMP treatment are permitted if serum 
total IgG value is <1g/L (Section 10.22).  
In the event of drug-related AEs, other than those that meet the IMP discontinuation criteria (as 
defined in Section 7.1) a dose reduction is permitted. Drug-related adverse events due to which 
dose modifications are recommended, may include, but are not limited to: 
• Moderate to severe headaches (Appendix 20, Section 10.20) 
• Severe vomiting and diarrhea (Appendix 21, Section 10.21) 
• Moderate to severe toxicities (Grade 2 and above, as defined by Common Terminology 
Criteria for Adverse Events version 5.0) for which rozanolixizumab cannot be excluded 
as a cause 
The date and reason for dose change of rozanolixizumab is to be recorded on each study 
participant’s eCRF. 
6.6 
Self-administration 
Self-administration will be offered to the study participant, if desired by the participant and 
approved by the investigator. Self-administration can occur at home or onsite, provided the 
participant is willing to do so and has received appropriate training. Training consists of different 
sessions performed by the study nurses, in which the patient would be made familiar with the 
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process. Only after the healthcare professional (HCP) confirms that the patient is considered 
adequately prepared to perform self-administration, a checklist will be completed and filed in the 
medical chart. Once all of the above is completed, the patient can perform the self-
administration. Self-administration will ONLY occur under the supervision of a fully trained 
HCP (to confirm that study participant is proceeding correctly).  
Note: self-administration will be offered as an option to countries listed in Section 10.7.1. 
6.7 
Home visits 
During the 52-week Treatment Period, certain study visits such as dosing visits (by HCP or self-
administration), may be conducted at a participant’s home or other locations (eg, rehabilitation or 
day care centers, etc), if desired by the participant and approved by the investigator.  
Healthcare professional home visits will be conducted by a fully trained HCP and will follow the 
schedule of assessments and safety monitoring schedule as an onsite visit. Eligibility for home 
visits includes the following: the study participant is deemed a suitable candidate by the 
investigator; the study participant is willing to be seen, dosed and monitored at home by a home 
nurse, and the study participant has shown good tolerability to previous 6 administrations of 
rozanolixizumab at the site (including, but not limited to, no moderate or severe infusion 
reactions, nor any AEs that the investigator considers unsuitable for home administration). A 
further prerequisite for dosing during a home visit is that the platelet counts were stable during 
the last four dosing visits (between ≥50 to ≤150×109/L) and that the dose administered during the 
last four dosing visits was not changed and is not planned to be changed at the home dosing visit. 
Study participants should not have experienced any ITP signs and symptoms or AEs since the 
last dosing visit. 
The investigator will be asked to complete a checklist confirming all criteria have been fully 
evaluated. This checklist will be shared with the UCB study physician or designee and reviewed 
before the first home visit for IMP administration can take place.  
6.8 
Treatment after the end of the study 
Study participants who complete participation in TP0004 may have the possibility to continue 
receiving rozanolixizumab through a Managed Access Program (MAP) if available, as indicated 
by the Sponsor and applicable per local regulations. 
7 
DISCONTINUATION OF IMP AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of IMP 
7.1.1 
Liver chemistry stopping criteria 
Discontinuation of IMP for abnormal liver function should be considered by the investigator 
when a study participant meets one of the conditions outlined in Figure 7-1 or if the investigator 
believes that it is in the best interest of the participant. 
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Figure 7-1: Phase 3-4 liver chemistry stopping criteria and increased monitoring 
algorithm 
 
ALT=alanine aminotransferase; INR=International Normalized Ratio; ULN=upper limit of normal 
Treatment with IMP may be continued with increased monitoring if a study participant meets 
one of the criteria outlined in Figure 7-2. 
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Figure 7-2: Liver chemistry increased monitoring algorithm with continued study 
intervention for participants with ALT ≥3xULN but <8xULN 
  
ALT=alanine aminotransferase; bili=bilirubin; ULN=upper limit of normal 
Specific assessments and follow-up actions for potential drug-induced liver injury (PDILI) are 
provided in Appendix 5, Section 10.5. 
7.1.2 
QTc stopping criteria 
A participant who meets either bulleted criterion based on the ECG readings will be withdrawn 
from IMP and move into the SFU Period. The study participant should be referred to a specialist 
(ie, cardiologist) and managed as per local guidance.   
• Corrected QT interval (QTc) >500ms OR uncorrected QT >600ms 
• Change from Baseline of QTc >60ms 
For participants with underlying bundle branch block, follow the discontinuation criteria listed 
below: 
Baseline QTc with bundle branch 
block 
Discontinuation QTc threshold with bundle branch 
block 
<450ms 
>500ms 
450 to 480ms 
≥530ms 
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QTc=corrected QT interval 
If a clinically significant finding is identified (including, but not limited to changes from 
Baseline in QT interval corrected for heart rate according to Fridericia's formula) after 
enrollment, the investigator or qualified designee will determine if the participant can continue in 
the study and if any change in participant management is needed. This review of the ECG 
printed at the time of collection must be documented. Any new clinically relevant finding should 
be reported as an AE. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that need to be completed. 
7.1.3 
Discontinuation of IMP due to other adverse events or medical 
condition 
Study participants MUST permanently discontinue IMP if they develop an illness that would 
interfere with his/her continued exposure to IMP including, but not limited to:  
− Study participant has a significant infective episode including but not limited to 
bacteremia or sepsis, infectious meningitis, osteomyelitis, septic arthritis, complicated 
pneumonia or visceral abscess which may or may not result in hospitalization. This list is 
not intended to be all inclusive and the investigator is expected to apply his/her judgment 
on continuing IMP based on the clinical situation at hand (see Appendix 22, 
Section 10.22). 
− Study participant has new onset or recurrent neoplastic disease (except for superficial 
basal or squamous cell carcinoma of the skin not requiring targeted biological therapy, 
chemotherapy or radiation). 
− Study participant has an AE of severe or serious hypersensitivity, infusion related 
reaction (see Appendix 23, Section 10.23) or anaphylaxis requiring corticosteroid and/or 
epinephrine therapy (see Appendix 19, Section 10.19) (Sampson et al, 2006). 
− Study participant has a serious AE of headache or GI disturbance that is considered 
related to the IMP in the opinion of the investigator; or recurrence of severe AE of GI 
disturbance (see Appendix 21, Section 10.21) or headache (see Appendix 20, 
Section 10.20) that is considered related to the IMP in the opinion of the investigator. 
− Study participant has a life-threatening bleeding event. 
− Study participant has an AE of arterial or venous thromboembolic event (eg, stroke, 
myocardial infarction, pulmonary embolism, deep vein thrombosis). 
− Study participant has a tuberculosis (TB) test that is confirmed positive or any further 
evidence suggestive of potential TB infection (eg, close exposure) and further 
examinations result in a diagnosis of active TB or latent TB (LTB), or nontuberculous 
mycobacterial infection (NTMBI) (see Section 8.1.5).  
− If a NTMBI is identified during the study, the same withdrawal procedures as those used 
for an active TB infection identified during the study should be followed. 
− Study participant requires rescue therapy (for exceptions, refer to Section 6.4.3). 
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Study participants who permanently discontinue IMP during the Treatment Period and hence are 
withdrawn from the study should complete the assessments outlined for the EW Visit and enter 
the SFU Period. 
7.1.4 
Temporary IMP discontinuation  
Study participant MUST temporarily discontinue IMP if any of the following events occur: 
1. Thrombocytosis (platelet count of ≥400×109/L). 
2. In the event of confirmed coronavirus disease (COVID-19) infection (eg, signs/symptoms 
such as fever, cough, shortness of breath), or known exposure sufficient to necessitate 
testing or self-imposed quarantine. The IMP may be restarted if: 
a. COVID-19 test is negative, and signs and symptoms have resolved 
b. If test is not available, resolution of signs and symptoms and 14 days have passed since 
initial presentation of the clinical signs/symptoms.  
c. If asymptomatic, 14 days have elapsed since known exposure.  
Study participant MAY temporarily discontinue IMP if any of the following events occur: 
1. A severe AE of headache that is considered related to the IMP in the opinion of the 
investigator (Section 10.20).  
2. A splenectomised study participant develops a (persistent or re-occurring) nonserious 
infection, as per investigator’s decision (Section 10.22). 
3. Total serum IgG values goes <1g/L as per investigator’s decision (Section 10.22). As IMP 
treatment is administered 
 the decision is based on the most recently available total 
IgG value. In order to maintain the blind from the parent studies, IgG, IgG subclasses, total 
protein, and albumin values will be unblinded starting with the blood samples taken at 
Week 4 (Visit 5). Additionally, guidance for investigators on management of infections can 
be found in Appendix 22, Section 10.22.  
7.2 
Participant discontinuation/withdrawal from the study 
Study participants are free to withdraw from the study at any time, without prejudice to their 
continued care. Participants who withdraw from the study should complete the EOS visit. 
A study participant may also be withdrawn from the study at any time at the discretion of the 
investigator for safety, behavioral, compliance, or administrative reasons. 
If the study participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
If a study participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
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Study participants must be withdrawn from the study and permanently discontinued from IMP if 
any of the following events occur: 
1. Participant withdraws his/her consent. 
2. Study participant takes prohibited concomitant medications as defined in this protocol. 
3. Study participant meets the mandatory IMP discontinuation criteria as per Section 7.1.1, 
Section 7.1.2 or Section 7.1.3. 
4. There is confirmation of a pregnancy during the study, as evidenced by a positive 
pregnancy test. 
5. The sponsor or a regulatory agency requests withdrawal of the study participant. 
Study participants who withdraw from the study or permanently discontinue IMP during the 
Treatment Period should complete the assessments outlined for the EW Visit, enter the SFU 
Period and complete the EOS Visit.  
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a participant in advance. Study participants who are withdrawn will not be replaced. 
7.3 
Lost to follow-up 
A study participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (at least 1 phone call and 1 written message 
to the participant), and document his/her effort (date and summary of the phone call and copy 
of the written message) in the source documents. 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up documented in the eCRF. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities (Section 1.3). 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the sponsor (or designee - Medical Monitor 
at contract research organization [CRO]) immediately upon occurrence or awareness to 
determine if the participant should continue or discontinue IMP. 
Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct. 
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Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for Baseline purposes provided the 
procedures met the protocol-specified criteria and were performed within the time frame defined 
in the Schedule of Activities (Section 1.3). 
An Unscheduled Visit can be conducted at the discretion of the investigator (eg, due to an AE). 
During the Unscheduled Visit, the following assessments will be performed: 
• AE reporting 
• Concomitant medications  
• Review of withdrawal criteria 
• Physical examination 
• Vital signs 
• Blood samples for PK, IgG, hematology, biochemistry, other testing such as for TB or 
C-reactive protein (CRP) as clinically indicated in the opinion of the investigator 
Other assessments may be performed at the discretion of the investigator.  
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 
Some study-specific investigations may not be conducted according to the study protocol during 
a pandemic or other exceptional circumstances (eg, hurricanes) due to the need to implement 
safety measures and guidance from regulatory authorities. In such a situation, which may be 
accompanied by local or global containment or other measures, sites may need to prohibit access 
to study participants and study-related personnel. Study participant visits to the study site may be 
replaced by contingency measures. These measures are primarily established to ensure the safety 
of study participants during the course of the study and to maintain the study participants 
treatment schedule, if the investigator considers it appropriate. These measures include but are 
not limited to virtual visits or home-nursing visits replacing site visits, eg, telemedicine contacts 
or home-nursing visits when treatment and/or blood sampling is scheduled. The contingency 
measures are described in a contingency plan which will be maintained by UCB for the 
respective study. The contingency measures are shared with the investigator and the respective 
study-related personnel as soon as there are indications that it is necessary to implement any of 
the measures. 
8.1 
Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). 
8.1.1 
Physical examination 
A full physical examination will include, at a minimum, assessments of general appearance; ear, 
nose, and throat; eyes, hair, and skin; assessments of the cardiovascular, respiratory, GI, 
neurological, musculoskeletal, and hepatic systems; and mental status.  
A short physical examination will include, at a minimum, assessments of general appearance; 
ear, nose, and throat; skin, respiratory, GI, and neurological systems. 
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For full and short physical examinations, investigators should pay special attention to clinical 
signs related to previous serious illnesses as well as signs and symptoms of infections. 
Clinically relevant findings or worsening of previous findings will be recorded as AEs. 
8.1.2 
Vital signs 
Oral, tympanic, or axillary temperature, pulse rate, and BP will be assessed. 
Blood pressure and pulse measurements will be assessed in a sitting position with a completely 
automated device. Manual techniques will be used only if an automated device is not available. 
Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the 
participant in a quiet setting without distractions (eg, television, cell phones). 
Vital signs (to be taken before blood collection for laboratory tests) will include 1 pulse, 1 BP 
and body temperature measurement. 
8.1.3 
Electrocardiograms 
12-lead ECGs will be obtained as outlined in the Schedule of Activities (Section 1.3) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals. Refer to Section 7.1.2 for QTc withdrawal criteria and any additional QTc readings 
that may be necessary. 
Central reading of ECGs will be performed, but for the assessment of the ECGs during the visit, 
the assessment of the investigator or designee will be used to determine eligibility and 
continuation in the study. 
All ECG recordings should be taken prior to blood collection for assessment of laboratory 
parameters, with the study participant resting in the supine position for at least 5 minutes before 
the recording. 
8.1.4 
Clinical safety laboratory assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and the 
Schedule of Activities (Section 1.3) for the timing and frequency. 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those that are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the participant's condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated until the values return to normal or Baseline or are no longer 
considered clinically significant by the investigator or Medical Monitor. 
If such values do not return to normal or Baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified. 
All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), must be 
conducted in accordance with the laboratory manual and the Schedule of Activities (Section 1.3). 
If laboratory values from nonprotocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
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clinically significant by the investigator (eg, SAE, AE, or dose modification), then the results 
must be recorded in the eCRF. 
8.1.5 
Assessment and management of TB and TB risk factors 
Precautions are being taken within this protocol to monitor the risk of TB infection in this study. 
Any presumptive diagnosis or diagnosis of a TB infection is a reportable event. Assessment and 
management of TB and TB risk factors should follow local/national guidelines. 
8.1.5.1 
Tuberculosis assessment 
Monitoring for TB during the study 
Study participants will be monitored for signs/symptoms of TB using routine pharmacovigilance 
measures for AEs. Study participants reporting AEs related to signs/symptoms of TB will be 
evaluated for LTB and active TB according to the local medical practice guidelines. 
Confirmed LTB, active TB, and NTMBI must be reported to UCB immediately regardless of 
seriousness using the SAE Report Form. Additional information received by the investigator 
should be provided within 24 hours of awareness. 
Once withdrawn from study treatment, study participants should return for the EW and complete 
all EOS assessments. 
TB signs and symptoms questionnaire 
Study participants will be evaluated both for signs and symptoms of latent or active TB infection 
and for risk factors for exposure to TB using the TB questionnaire (Appendix 18, Section 10.18) 
as indicated in the Schedule of Activities (Section 1.3). 
The TB questionnaire at study entry of TP0004 will not be collected. The TP0003 or TP0006 
Week 25 (Visit 27) questionnaire will be used as the study entry questionnaire for TP0004. 
The TB questionnaire be completed accurately and filed as a critical source document. The 
questionnaire will assist with the identification of participants who may require therapy for TB. 
A “Yes” response to any of the questions in the TB questionnaire may trigger further 
assessments to determine if the participant has either latent TB infection (LTBI) or active TB 
infection and, if confirmed, must be withdrawn from the study. As an example, a participant who 
answered “Yes” to the question “
 
 
should not be allowed into the study pending further assessments per local/national 
guidelines. 
8.1.5.2 
Tuberculosis management 
In line with the World Health Organization (WHO) and the Centers for Disease Control and 
Prevention (CDC) guidelines, UCB has adopted the following definitions for latent TB, active 
TB and non-tuberculosis mycobacterium infection for the purposes of its clinical trials. 
Latent TB 
Latent TB infection is defined an infection by Mycobacterium tuberculosis with: 
• a positive IGRA test or 2 indeterminate IGRA tests AND 
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• a chest x-ray [or other imaging]) negative for TB infection AND 
• the absence of signs, symptoms (eg, evidence of organ specific involvement, or physical 
findings) suggestive of TB infection. 
Active TB and non-tuberculosis mycobacterium infection 
A clinically verified case of TB meets the following criteria: 
• a positive Tuberculin Skin Test (TST) or positive IGRA for Mycobacterium tuberculosis  
• other signs and symptoms compatible with TB (eg, abnormal chest radiograph, abnormal 
chest computerized axial tomography scan or other chest imaging study, or other clinical 
evidence of active disease) 
Nontuberculous mycobacterium infection (NTMBI) is defined as a clinical infection caused by 
mycobacterial species other than those belonging to the Mycobacterium tuberculosis complex. 
Study participants who develop active TB or NTMBI during the study must be withdrawn from 
the study. The participant must be permanently discontinued from study medication and the EW 
Visit must be scheduled as soon as possible, but no later than the next scheduled visit.  
Participants should be encouraged to enter the SFU Period, and keep the EOS Visit as specified 
by the protocol. Treatment for active TB or NTMBI should be started immediately based on 
local guidelines. 
Confirmed active TB is always considered an SAE. UCB’s process requires that this must be 
captured on an SAE report form and provided to UCB in accordance with SAE reporting 
requirements. Follow-up reports should be completed as per protocol requirement until such time 
as the TB infection resolves. 
LTBI, active TB, or other NTMBI identified during study 
During the study, study participants who develop evidence of LTBI, active TB or NTMBI must 
immediately stop further administration of IMP and will be referred to an appropriate TB 
specialist (pulmonologist or infectious disease specialist) for further evaluation. Participants 
diagnosed with active TB treatment or LTBI should receive appropriate TB treatment or 
prophylaxis therapy. The participant should be transferred to the care of their physician and 
managed according to the standard of care. 
If an NTMBI is identified during the study, the same procedure as for active TB acquired during 
the study and compliant TB treatment shall be followed. 
Follow-up information of suspected and confirmed TB cases should be provided to UCB at least 
after 3, 9, and 12 months of the start date of anti-TB treatment, including hematological and 
biochemical safety parameters, x-ray evolution data, and TB diagnostic procedures used to 
follow-up and confirm recovery of TB. 
8.1.6 
Splenectomized study participants 
Asplenic study participants will be required to carry a splenectomy card for the whole duration 
of the study indicating they have undergone splenectomy and may be at increased risk of 
infection particularly with encapsulated organisms. Prophylactic antibiotic may be given to these 
participants, if required per local guidance. Antibody titers against S. pneumoniae, N. 
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meningitidis, and H. influenzae in splenectomized study participants will be measured at the 
defined time points as specified in the Schedule of Activities. 
Splenectomized study participants should have documented evidence of vaccinations from the 
parent studies against the following encapsulated organisms: S. pneumoniae, N. meningitidis, and 
H. influenzae (as per local/or a national guidance, as applicable) or as evidenced from personal 
immunization records. 
8.2 
Adverse events 
The definitions of an AE or SAE can be found in Appendix 3, Section 10.3. 
Adverse events can be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the IMP or study procedures, or that caused the participant 
to discontinue rozanolixizumab or TP0004 (see Section 7). 
8.2.1 
Time period and frequency for collecting AE and SAE information 
All AEs and SAEs will be collected from the signing of the ICF until the EOS Visit at the time 
points specified in the Schedule of Activities (Section 1.3). 
All SAEs will be recorded and reported to the sponsor or designee within 24 hours, as indicated 
in Appendix 3, Section 10.3. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available. 
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 participant, and to also inform participants 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. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3, Section 10.3. 
8.2.2 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.2.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs and nonserious AEs of special interest (as defined in 
Section 8.2.7) will be followed until resolution, stabilization, the investigator determines that it is 
no longer clinically significant, the event is otherwise explained, or the participant is lost to 
follow-up (as defined in Section 7.3). Further information on follow-up procedures is given in 
Appendix 3, Section 10.3. 
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8.2.4 
Regulatory reporting requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the IMP under 
clinical investigation are met. 
UCB has a legal responsibility to notify both the local regulatory authority and other regulatory 
agencies about the safety of the IMP under clinical investigation. UCB will comply with 
country-specific regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.2.5 
Pregnancy 
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of IMP and until 90 days after the final dose. 
If a pregnancy is reported, the investigator must immediately inform UCB within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4, 
Section 10.4. 
The participant should be withdrawn from the study as soon as pregnancy is known (by positive 
pregnancy test), and the following should be completed: 
• The participant should immediately stop the intake of the IMP. 
• The study participant should return for the EW Visit and complete the SFU Period. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.2.6 
Anticipated serious adverse events 
The following anticipated SAEs are anticipated to occur in the population studied in this protocol 
at some frequency that is independent of drug exposure (Table 8-1). 
This list does not change the investigator’s obligation to report all SAEs (including anticipated 
SAEs) as detailed in Section 8.2.1 and Appendix 3, Section 10.3. 
Table 8-1: 
Anticipated serious adverse events for ITP population 
Anemia 
Hemorrhagic events 
Fatigue 
Thrombocytopenia 
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8.2.7 
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 
participant. 
See Appendix 5, Section 10.5 for further information on liver safety monitoring. 
8.2.8 
Adverse events of special monitoring 
For rozanolixizumab, AESM that require immediate reporting (within 24 hours regardless of 
seriousness) to UCB are: 
• Severe headache 
• Severe GI disorders (ie, diarrhea, abdominal pain, vomiting) 
• Opportunistic infection 
• Arterial and venous thrombotic and thromboembolic events 
An AESM is not necessarily a serious adverse event unless one of the seriousness criteria 
defined in the Appendix 3 (Section 10.3) is met. All AESM will follow the SAE recording and 
reporting procedures as indicated in Appendix 3, Section 10.3. 
In case of moderate or severe headache or serious headache (regardless of severity), the 
headache questionnaire (Appendix 17, Section 10.17) must be completed, though moderate 
headache is not considered an AESM. Additional procedures for management of headaches are 
provided in Appendix 20, Section 10.20. 
Procedures for the management of diarrhea is provided in Appendix 21, Section 10.21. 
Although hypersensitivity reactions including infused-related reactions and anaphylaxis are not 
classified as AESM, these AEs will be monitored by the investigators. If such an event is 
suspected it should be managed according the guidance provided in Appendix 23, Section 10.23. 
In case of suspected anaphylaxis, the Sampson Criteria (Sampson et al, 2006) (Appendix 19, 
Section 10.19) should be completed. All hypersensitivity reactions will be recorded and reported 
as per the AE reporting procedure outlined in Appendix 3, Section 10.3. 
8.2.9 
COVID-19 vaccination 
COVID-19 vaccines will be recorded on the concomitant medication eCRF page (Section 6.4.1). 
If an AE is considered related to COVID-19 vaccine, causality assessment should be entered on 
the AE eCRF (in the AE eCRF page, there is the possibility to assess causality to the IMP or to 
any concomitant medication). Note that in this case, the national recommendation for reporting 
adverse event related to COVID-19 vaccines should be followed. 
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If an AE is the result of an interaction of a COVID-19 vaccine with the IMP in the clinical study 
then the causal association should be for both IMP and COVID-19 vaccine. In case of a 
seriousness criteria, the SUSAR process will be followed. 
8.3 
Safety signal detection 
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 participants, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
In addition, an IDMC will periodically review and monitor safety data from this study and advise 
UCB. Details are provided in the IDMC Charter. 
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the Patient Safety 
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. 
8.4 
Treatment of overdose 
For this study, any dose increase of 10% or greater than the assigned dose for each administered 
dose of IMP will be considered an overdose, irrespective of the weight tier band. Overdose 
events are only considered AEs or SAEs if there are associated clinical signs and symptoms or if 
the act of taking the excess IMP itself is an AE or SAE (eg, suicide attempt). 
UCB does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator/treating physician should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities for at least 
5 days. 
3. Obtain a plasma sample for PK analysis within 3 days from the date of the final dose of 
IMP if requested by the Medical Monitor (determined on a case-by-case basis). 
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
8.5 
Efficacy assessments 
8.5.1 
Platelet counts 
As in the parent studies, TP0003 and TP0006, for assessment of platelet counts, blood samples 
will be collected by qualified site personnel at the same time that samples are collected for 
standard clinical laboratory assessments. The time and date of the blood draws will be recorded 
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in medical source data and the eCRF. Assessment will be performed according to the Schedule 
of Activities (Section 1.3). 
Platelet counts will be determined at local laboratories and the following endpoints will be 
derived for the purpose of analysis. 
Platelet count-related endpoints are: 
• Stable Clinically Meaningful Response, defined as Clinically Meaningful Response (ie, 
platelet count ≥50×109/L) without rescue therapy at ≥70% of the visits over the planned 52-
week Treatment Period starting at Week 4 
• Stable Response, defined as platelet count ≥30×109/L and absence of bleeding without rescue 
therapy at ≥70% of the visits over the planned 52-week Treatment Period starting at Week 4 
• Cumulative number of weeks with Clinically Meaningful Response over the planned 52-
week Treatment Period 
• Cumulative number of weeks with platelet counts ≥30×109/L over the planned 52-week 
Treatment Period 
• Mean Change from Baseline in platelet count at each visit 
• Use of rescue medication by visit 
• ITP-BAT bleeding events and severity by visit 
Platelet endpoints in study participants with first exposure to rozanolixizumab: 
• In study participants with first exposure to rozanolixizumab: Durable Clinically Meaningful 
Platelet Response of ≥50×109/L, for at least 4 of 6 
visits between Weeks 13 to 25 
of the study. 
• In study participants with first exposure to rozanolixizumab: Time to first Clinically 
Meaningful Platelet Response of ≥50×109/L: time from starting treatment to achievement of 
first response of ≥50×109/L. 
The clinical response variables will be assessed only for visits for which both platelet counts and 
the ITP bleeding score are assessed (with the exception of the confirmatory platelet assessments, 
which may be obtained at any visit [scheduled or unscheduled] provided that they meet the 
criteria below). In order to define a Response (platelet count ≥30×109/L), the platelet count must 
be confirmed on 2 consecutive occasions and in the absence of bleeding. The time to first 
Response will be taken as the time to the first platelet assessment (obtained at the same time as 
the corresponding ITP bleeding score assessment). If the second assessment does not fulfill the 
required criteria for a Clinical Response, the study participant will be considered as a 
nonresponder at the respective visits. Further details will be provided in the Statistical Analysis 
Plan (SAP). 
8.5.2 
ITP bleeding score 
The International Working Group on ITP proposes a consensus-based ITP-BAT, based on a 
precise definition of bleeding manifestations and on the grading of their severity (Rodeghiero et 
al, 2013). The ITP bleeding score will be assessed using the ITP-BAT tool Version 1.0. This 
assessment will be performed according to the Schedule of Activities (Section 1.3). 
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For the ITP-BAT, bleeding manifestations were grouped into 3 major domains: skin (S), visible 
mucosae (M), and organs (O), with gradation of severity (SMOG). Each bleeding manifestation 
is assessed at the time of examination. Severity is graded from 0 to 3 or 4, with Grade 5 for any 
fatal bleeding. Bleeding reported by the participant without medical documentation is Grade 1. 
Within each domain, the same grade is assigned to bleeding manifestations of similar clinical 
impact. The “worst” bleeding manifestation since the last visit is graded, and the highest grade 
within each domain is recorded. The SMOG system provides a consistent description of the 
bleeding phenotype in ITP. 
A standardized data collection form will be used to facilitate collection of information and 
communication among physicians and investigators. The grading of bleeding symptoms at 
presentation and at each subsequent evaluation is presented in Appendix 10, Section 10.10. 
8.5.3 
Patient Reported Outcomes 
Patient reported outcomes must be completed as per time points mentioned in the Schedule of 
Activities (Section 1.3). The PROs should be completed prior to any intrusive procedures in a 
quiet place. On dosing days, PROs will be completed prior to dosing. 
The PROs should be completed in the following order: ITP-PAQ, SF-36, the FATIGUE-PRO 
Physical Fatigue Scale, EQ-5D-5L, PGI-S, and PGI-C. 
8.5.3.1 
ITP-PAQ 
The ITP-PAQ is a 44-item disease-specific quality of life (QoL) questionnaire developed for use 
in adults with chronic ITP. It includes 11 scales: Symptoms, Fatigue, Physical Health – Bother, 
Physical Health - Activity, Emotional Health – Psychological, Emotional Health – Fear, Overall 
QoL, Social Activity, Women’s Reproductive Health – Fertility, Women’s Reproductive 
Health - Menstrual Symptoms, and Work. Each item is rated on a Likert-type scale containing 
4 to 7 responses. All item scores are transformed to a 0 to 100 continuum and are weighted 
equally to derive individual scale scores. Higher scores indicate better health status 
(Mathias et al, 2009; Mathias et al, 2007). 
The ITP-PAQ Symptoms score was selected as secondary efficacy endpoint for the study to 
capture the benefits of rozanolixizumab in terms of patient-perceived symptoms. It covers 6 core 
symptoms of ITP: bruising/petechiae, wounds/scars (from blood tests, injections or iv needles), 
blood blisters in mouth, bleeding episodes, muscle aches, and cramps in legs. 
The ITP-PAQ sample questionnaire is available in Appendix 11, Section 10.11. 
8.5.3.2 
SF-36 
Study participants will complete the SF-36 questionnaire according to the Schedule of Activities 
(Section 1.3). The SF-36 sample questionnaire is available in Appendix 12, Section 10.12. 
8.5.3.3 
FATIGUE-PRO Physical Fatigue Scale 
The FATIGUE-PRO Physical Fatigue Scale is one of the three scales of the broader FATIGUE-
PRO instrument developed by UCB. It consists of 9 items rated on a 5-point frequency response 
scale ranging from “none of the time” to “all of the time”, with a 7-day recall period. The 
FATIGUE-PRO Physical Fatigue score ranges 0 to 100, with a higher score meaning more 
physical fatigue.  
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The Physical Fatigue is available in Appendix 13, Section 10.13. 
8.5.3.4 
EQ-5D-5L 
The EQ-5D-5L is designed to improve the instrument’s sensitivity and to reduce ceiling effects. 
The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EuroQoL visual 
analog scale (EQ VAS). 
The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight 
problems, moderate problems, severe problems, and extreme problems. The study participant is 
asked to indicate his/her health state by ticking the box next to the most appropriate statement in 
each of the 5 dimensions. This decision results in a 1-digit number that expresses the level 
selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit 
number that describes the study participant’s health state. 
The EQ VAS records the study participant’s self-rated health on a vertical visual analog scale 
(VAS), where the endpoints are labeled ‘The best health you can imagine’ and ‘The worst health 
you can imagine’. The VAS can be used as a quantitative measure of health outcome that reflect 
the study participant’s own judgment. 
Study participants will complete the EQ-5D-5L questionnaire according to the Schedule of 
Activities (Section 1.3). The EQ-5D-5L sample questionnaire is available in Appendix 14, 
Section 10.14. 
8.5.3.5 
PGI-S 
The PGI-S is a single-state, self-report measure that rates a study participant's severity of a 
specific condition. The PGI-S is a 5-point scale depicting a study participant's rating of overall 
symptoms (“none,” “mild,” “moderate,” “severe,” or “very severe”). The PGI-S sample 
questionnaire is available in Appendix 15, Section 10.15. 
8.5.3.6 
PGI-C 
The PGI-C is a single-state, self-report measure that reflects a study participant's belief about the 
efficacy of treatment for a specific condition. The PGI-C is a 7-point scale depicting a study 
participant's rating of overall improvement (“very much improved,” “much improved,” 
“minimally improved,” “no change,” “minimally worse,” “much worse,” or “very much worse”). 
The PGI-C sample questionnaire is available in Appendix 16, Section 10.16. 
8.5.3.7 
SIAQ (Infusion version) 
To assess the experience of study participants with the sc self-administration using an infusion 
device, an adaptation of the SIAQ will be used in the participants that self-administer.  
The SIAQ was developed by UCB to assess the perceived advantages and the potential 
limitations of self-administration of an sc medication (Keininger and Coteur, 2011). There are 2 
modules for the SIAQ (SIAQ PRE-Self-Injection and SIAQ POST-Self-Injection). The SIAQ 
PRE-Self-Injection is composed of 7 items grouped into 3 domains (feelings about injection, 
self-confidence, and satisfaction with the current mode of administration). The SIAQ POST-
Self-Injection is composed of 21 items grouped into 6 domains (feelings about injection, self-
image, self-confidence, injection site reactions, ease of use, and satisfaction with self-injection). 
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Each domain score of the SIAQ PRE-Self-Injection and SIAQ POST-Self-Injection ranges from 
0 to 10, 0 being the worst experience and 10 being the best experience.  
The adaptation of the SIAQ consists in replacing the terminology “injection” with the 
terminology “infusion” in both modules, and removing the “ease of use” domain which is not 
accurate for the self-administration method used in the study from the SIAQ POST-Self-
Injection module. This adapted version is named SIAQ (Infusion version). The domain scores of 
the SIAQ (Infusion version) are calculated the same way as the SIAQ domain scores; hence 
domain scores ranges from 0 to 10, 0 being the worst experience and 10 being the best 
experience. 
The PRE-SIAQ (Infusion version) will be completed once before the first self-administration, 
and the POST-SIAQ (Infusion version) will be completed within 1 hour after self-administration 
at consecutive visits. Paper versions will be used. The sample questionnaires are available in 
Appendix 24, Section 10.24.  
8.6 
Pharmacokinetics and antidrug antibodies 
Whole blood samples will be collected for measurement of plasma concentrations of 
rozanolixizumab and ADA as specified in the Schedule of Activities (Section 1.3). Blood 
samples may be collected at additional time points during the study if warranted and agreed upon 
between the investigator and the sponsor. Instructions for the collection and handling of 
biological samples will be provided in the laboratory manual for this study. The actual date and 
time (24-hour clock time) of each sample will be recorded. 
Samples will be used to evaluate the PK of rozanolixizumab and ADA and may be used for 
establishing assay parameters (eg, ADA cut point setting and PK selectivity assessment). 
Samples collected for analyses of rozanolixizumab concentration may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study. 
Participant confidentiality will be maintained. At visits during which whole blood samples for 
the determination of rozanolixizumab PK and ADA will be taken, one sample of sufficient 
volume can be used. 
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and then archived in the sponsor and site study files, but will not constitute a 
protocol amendment. The IRB/IEC will be informed of any safety issues that require alteration 
of the safety monitoring scheme or amendment of the ICF. 
8.7 
Pharmacodynamics 
Venous blood samples will be collected at time points specified in the Schedule of Activities 
(Section 1.3) for measurement of: 
• Serum IgG and IgG subclasses concentrations 
• Serum IgA, IgE, and IgM concentrations 
• Serum ITP-specific autoantibodies 
For all PD assessments, blood samples will be collected predose. Instructions pertaining to 
sample collection, processing, storage, labeling, and shipping are provided in the laboratory 
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manual for this study. Results of the ITP-specific autoantibodies analyses may not be outlined in 
the Clinical Study Report for this study, but in a separate report. 
8.8 
Exploratory biomarkers 
Collection of samples for exploratory biomarker research is also part of this study. Blood 
samples for biomarker research are required and will be collected from all study participants in 
this study as specified in the Schedule of Activities (Section 1.3). Exploratory samples will be 
collected predose. Additional exploratory biomarker samples may be collected 4 hours postdose 
in case of severe and/or serious headache or GI-related AESM as specified in the Schedule of 
Activities (Section 1.3). 
Protein and metabolites biomarkers such as but not limited to albumin, B-cell activating factor, 
and circulating immune complexes may be measured to assess the effect of rozanolixizumab on 
exploratory biomarkers, and explore the relationship between protein and metabolite biomarkers 
and cause, progression, and appropriate treatment of ITP. 
If not used immediately, these samples will be stored at -80°C for up to 20 years for later 
exploratory analyses. Any exploratory biomarker will only ever be related to the exploration of 
cause, progression, and appropriate treatment of ITP. They may also be used to develop 
tests/assays including diagnostic tests related to rozanolixizumab and/or FcRn inhibitor and ITP. 
The nature and format of these tentative additional analyses will be determined at a later time. 
Details on the collection, storage, preparation, and shipping of samples will be presented in the 
laboratory manual provided separately. Detailed information on sample analyses will be 
provided in a bioanalytical report. Results of the DNA and RNA biomarker analyses will not be 
outlined in the Clinical Study Report for this study. 
8.9 
Immunology biomarkers 
Blood samples for immunological testing are required and will be collected from all study 
participants in this study as specified in the Schedule of Activities (Section 1.3) for measurement 
of: 
• Serum complements (C3, C4) 
• Plasma complements (C3a, C5a)  
• Biomarkers of COVID-19 vaccine response (only for study participants who received 
COVID-19 vaccine) 
Samples for serum complements (C3, C4) and plasma complements (C3a, C5a) will be collected 
predose at Baseline (Day 1) for all participants. Additional samples may be collected 2 hours and 
4 hours postdose for study participants with an infusion reaction or hypersensitivity reaction as 
specified in the Schedule of Activities (Section 1.3). 
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study. 
8.10 
Medical resource utilization and health economics 
Medical resource utilization will be collected by capturing number and length of hospitalizations 
and by capturing number of infusion center admissions. 
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9 
STATISTICAL CONSIDERATIONS 
A description of statistical methods follows and will be described in more detail in the SAP. 
9.1 
Definition of analysis sets 
• Enrolled Set: All study participants who have signed the informed consent. 
• Safety Set (SS): All study participants who received at least 1 dose of IMP (partial or full). 
Analysis of this set will be according to the treatment the participants actually received, and 
will be used for the for the efficacy, demographic, PK and safety analyses. 
• Pharmacokinetic Per-Protocol Set (PK-PPS): A subset of the Safety Set, consisting of those 
study participants who received at least 1 dose, and had at least 1 valid PK measurement. 
9.2 
General statistical considerations 
All analyses will be performed using SAS® version 9.2 or later (SAS Institute, Cary, NC, USA). 
Continuous variables will be summarized with statistics including the number of participants (n), 
mean, standard deviation, median, minimum, and maximum. Categorical variables will be 
summarized with frequency counts and percentages. 
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 dose of IMP, and 
measurement-specific Baseline values will be defined in the SAP. 
Data handling conventions for data affected by COVID-19 will be detailed fully in the SAP. 
9.3 
Estimands 
The aim of TP0004 is to investigate the safety (primarily) of long term treatment of 
rozanolixizumab.  
The primary safety analysis is based on a “treatment policy” estimand to allow for the inclusion 
of study participants that receive rescue medication. This estimand will be based on the SS who 
started TP0004 on 
 dosing. 
There is no analysis strategy to protect the type I error as there is no significance testing amongst 
the primary and secondary endpoints. 
The primary safety estimand will be defined as follows: 
• Population: participants with primary ITP that meet the protocol-specified 
inclusion/exclusion criteria and who started TP0004 on 
 dosing. 
• Participant-level outcome: occurrence of TEAEs. 
• Population-level summary measure: descriptive summaries. 
• Intercurrent event handling: The main intercurrent events are the use of rescue medication 
during the course of the study and withdrawal due to TEAEs. 
A further secondary safety estimand, also based on “treatment policy”, will use the SS who 
started TP0004 on 
dosing. It is defined as follows: 
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• Population: participants with primary ITP that meet the protocol-specified 
inclusion/exclusion criteria and who started TP0004 on 
dosing. 
• Participant-level outcome: occurrence of TEAEs. 
• Population-level summary measure: descriptive summaries. 
• Intercurrent event handling: The main intercurrent events are the use of rescue medication 
during the course of the study and withdrawal due to TEAEs. 
Missing safety values will not be imputed. 
Further details will be provided in the SAP. 
9.4 
Planned safety analyses 
The frequency and severity of all TEAEs will be presented by system organ class, high level 
term, and preferred term (Medical Dictionary for Regulatory Activities [MedDRA]®). The data 
will be displayed as number of participants experiencing the TEAE, percentage of participants, 
and number of TEAEs. A TEAE is defined as any event that was not present prior to 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, up to and including 8 weeks after 
the final dose of IMP. 
Laboratory evaluations, ECGs, and vital signs will be analyzed over time. 
All safety analyses will be based on the SS and be presented by both the treatment the 
participants received during the parent studies (TP0003/TP0006), and whether they started 
TP0004 on 
 dosing. 
9.5 
Planned efficacy/outcome analyses 
Data will be listed, and for continuous variables, descriptive statistics will be generated for the 
observed values and changes from Baseline. For categorical variables, frequency counts and 
percentages will be presented.  
All summary outputs will be presented by the treatment the participants received during the 
parent studies (TP0003/TP0006) and whether they started TP0004 on 
 
dosing. 
The key secondary endpoint in TP0004 for efficacy is stable clinically meaningful response 
defined as Clinically Meaningful Response (≥50×109/L platelet count) without rescue therapy at 
≥70% of the visits starting at Week 4, as it is anticipated that the effect of any rescue medication 
that might have been administered to the study participants in the placebo arm close to the end of 
the parent study would have dissipated at the time of assessing the stable clinically meaningful 
response in TP0004.  
The other platelet count-related efficacy endpoints are Stable Response (defined as platelet count 
≥30×109/L and absence of bleeding without rescue therapy) at ≥70% of the visits starting at 
Week 4; cumulative number of weeks with Clinically Meaningful Response; cumulative number 
of weeks with platelet counts ≥30×109/L and mean Change from Baseline in platelet count. 
These efficacy endpoints will be measured over time (52 weeks of treatment) in the same manner 
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as the key secondary endpoint. The Baseline platelet count is defined as platelet count at Visit 1 
(TP0004). 
Cumulative number of weeks with Clinically Meaningful Response and cumulative number of 
weeks with platelet counts ≥30×109/L will be also be presented for the first 24 weeks of the 
study. 
Platelet count data will be presented both as collected, and with imputation as follows: Missing 
platelet count at any visit will be considered "worst case" and set to zero ("no platelet response"). 
The same will apply to missing platelet count at any visit after the initiation of rescue therapy. 
Baseline platelet count for each endpoint will be defined in the SAP. Rescue therapy given to 
participants who received placebo in the parent studies to ensure platelet count >30×109/L will 
be summarized.  
Subgroup analyses split by rescue medication use in TP0003 and TP0006 may be conducted. 
Further details will be provided in the SAP. 
9.6 
Planned other analyses 
9.6.1 
Analysis of pharmacodynamics endpoints 
The analyses (potentially including, but not limited to albumin, and total IgG, IgG subclasses, 
IgA, IgE, IgM, serum complement, plasma complement, and ITP specific autoantibodies) will be 
presented as continuous variables. All PD and biomarker analyses will be based on the SS and by 
dosing regimen.  
9.6.2 
Analysis of pharmacokinetics endpoints 
All PK analyses will be based on the PK dataset. 
Individual concentrations of rozanolixizumab will be listed and may be summarized at each 
scheduled time point and may be stratified by ADA status and dose regimen when applicable. 
Descriptive statistics of concentrations will be calculated only if at least two-thirds of the 
individual data points are quantifiable at a certain time point (≥ lower limit of quantification 
[LLOQ]). For summary statistics, below the LLOQ will be represented as LLOQ/2. Individual 
concentrations may be depicted graphically as individual plots and/or spaghetti plots. The impact 
of ADA on rozanolixizumab concentrations will be evaluated. 
Further details will be provided in the SAP. 
9.6.3 
Antidrug antibodies analyses 
A tiered ADA approach will be used for the study. Samples will first be evaluated in the 
screening assay using a false positivity rate of 5% (reported as negative screen or positive 
screen), followed by analysis of screened positive samples in the confirmatory assay (which is a 
drug depletion assay) to confirm the true positivity of the samples (reported as negative 
immunodepletion or positive immunodepletion). Samples that are confirmed as positive will be 
evaluated in a titration assay to quantify the ADA level and will be reported as titer (reciprocal 
dilution factor including MRD). For anti-rozanolixizumab antibody positive samples (or subset 
of), further characterization for neutralizing ADA potential in vitro will be performed, and 
results will be presented in a listing. Full details will be provided in the SAP. 
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9.7 
Handling of protocol deviations 
Important protocol deviations are identified as part of the data cleaning process in the Data 
Cleaning Plan. Ongoing data cleaning meetings will be held throughout the duration of the study. 
Objectives of these meetings include the review of important protocol deviations and the update 
(if necessary) of the important protocol deviation specification. Furthermore, overall trends in 
protocol deviations will be discussed at the Data Evaluation Meetings. Through this ongoing data 
cleaning and evaluation process, all decisions regarding important protocol deviations are made 
on an ongoing basis. 
9.8 
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. 
9.9 
Planned interim analysis, data monitoring, and data snapshots 
9.9.1 
Interim analysis 
No formal interim analysis is planned for this study. 
In addition, based on data cutoffs, safety and efficacy data for submission purposes will be 
summarized. 
9.9.2 
Data monitoring 
An external IDMC will be established to review the safety data at predefined intervals and ad 
hoc as needed, should any emerging safety concern arise during the study. Details of the IDMC 
composition, processes, and responsibilities will be documented in the IDMC charter. Key safety 
data may be pooled at the discretion of the IDMC for protection of all study participants if 
warranted. 
The IDMC will consist of members independent from UCB. Study enrollment will not be halted 
during planned IDMC review of the safety and efficacy data. The objectives and procedures for 
the IDMC will be detailed in the IDMC Charter. 
9.9.3 
Data snapshots 
There will be periodic data snapshots for submission and market approval. 
9.10 
Determination of sample size 
No formal sample size calculation can be performed. All participants from the parent studies 
(TP0003 and TP0006) eligible for the OLE will be included. It is expected that up to a maximum 
of 180 participants will be included. 
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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
International Council for Harmonisation (ICH)-Good Clinical Practice (GCP), and in accordance 
with the ethical principles that have their origin in the Declaration of Helsinki. 
The investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the investigator/UCB will forward copies of the protocol, ICF, IB, 
investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all other 
participant-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 participants or others, and any protocol deviations, to 
eliminate immediate hazards to participants. 
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 participants. 
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 participant 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. 
10.1.2 
Financial disclosure 
Insurance coverage will be handled according to local requirements. 
Finance and insurance are addressed in the investigator and/or CRO agreements, as applicable. 
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10.1.3 
Informed consent process 
Participant’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 participant in both oral and written form by the investigator (or 
designee). Each participant will have the opportunity to discuss the study and its alternatives 
with the investigator. 
Prior to participation in the study, the ICF should be signed and personally dated by the study 
participant and by the person who conducted the informed consent discussion (investigator or 
designee) at the site. The study participant must receive a copy of the signed and dated ICF. As 
part of the consent process, each participant must consent to direct access to his/her medical 
records for study-related monitoring, auditing, IRB/IEC review, and regulatory inspection. 
If the ICF is amended during the study, the investigator (or UCB, if applicable) must follow all 
applicable regulatory requirements pertaining to the approval of the amended ICF by the 
IRB/IEC and use of the amended form. 
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form. 
The participant may withdraw his/her consent to participate in the study at any time. A 
participant is considered as enrolled in the study when he/she has signed the ICF. An eCRF must 
not be started, nor may any study specific procedure be performed for a given participant, 
without having obtained his/her written consent to participate in the study. 
10.1.4 
Data protection 
UCB staff (or designee) will affirm and uphold the participant’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the participant number 
assigned at Screening of the parent study (TP0003 or TP0006). 
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 
participant’s primary medical records that directly concerns this study (including, but not limited 
to, laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a participant’s study participation, and autopsy reports for deaths 
occurring during the study). 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.  
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
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10.1.5 
Committees structure 
An external IDMC will be established to mainly review the safety data at predefined intervals 
and ad hoc as needed, should emerging safety concerns arise during the study. The IDMC will 
have the possibility to unblind the data. Details of the IDMC composition, processes, and 
responsibilities will be documented in the IDMC Charter. 
10.1.6 
Data quality assurance 
All participant data relating to the study will be recorded in the eCRF. The investigator is 
responsible for verifying that data entries are accurate and correct by electronically signing the 
eCRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH-GCP, and all applicable regulatory requirements. 
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. 
Quality tolerance limits will be established for the study using parameters related to patient 
safety reporting and reliability of study results. The parameters will be monitored throughout the 
study to identify systematic issues. Parameters used, parameter values, important deviations from 
the quality tolerance limits, and actions taken will be summarized in the clinical study report. 
10.1.6.1 
Electronic 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. 
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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. 
10.1.6.2 
Apps 
Not applicable. 
10.1.7 
Source documents 
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 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, quality of life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area. 
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the investigator and become a permanent part of the participant’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). 
10.1.8 
Study and site closure 
The UCB designee reserves the right to close the study site or terminate the study at any time for 
any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further IMP development 
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10.1.9 
Publication policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows UCB to protect proprietary information and to provide comments. 
UCB will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, UCB will generally support publication of multicenter 
studies only in their entirety and not as individual site data. In this case, a coordinating 
investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
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10.2 
Appendix 2: Clinical laboratory tests 
• The tests detailed in Table 10-1 will be performed by the central laboratory, with the 
exception of platelet count assessments. 
• With the exception of platelet counts, local laboratory results are only required in the event 
that the central laboratory results are not available in time for either IMP administration 
and/or response evaluation. If a local sample is required, it is important that the sample for 
central analysis is obtained at the same time. Additionally, if the local laboratory results are 
used to make either a study treatment decision or response evaluation, the results must be 
entered into the eCRF. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5.1 and Section 5.2 of the protocol, respectively. 
• Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations. 
Table 10-1: Protocol-required safety laboratory assessments 
Laboratory 
Assessments Parameters 
Hematology 
Platelet Count (local 
laboratory) a 
Red blood cell (RBC) Indices: 
Mean corpuscular volume (MCV) 
Mean corpuscular hemoglobin (MCH) 
White blood cell 
(WBC) Count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Coagulation 
International  
Normalized Ratio 
(INR) b 
Activated partial thromboplastin time 
(aPTT) c 
Fibrinogen c 
Clinical 
Chemistryd 
Blood Urea Nitrogen 
(BUN) 
Potassium 
Aspartate 
Aminotransferase 
(AST)/Serum 
Glutamic-Oxaloacetic 
Transaminase 
(SGOT) 
Total and direct 
bilirubin 
Creatinine 
Sodium 
Alanine 
Aminotransferase 
(ALT)/Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT) 
Total Protein 
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Laboratory 
Assessments Parameters 
Glucose (fasting 
state preferred) 
Calcium 
Alkaline phosphatase 
C-reactive protein 
(CRP) 
Immunoglobulinse 
Albumin 
Low-density 
lipoprotein (LDL) 
High-density 
lipoprotein (HDL) 
Total cholesterol 
Triglycerides 
 
Routine 
Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Other Tests 
• 
Follicle-stimulating hormone and estradiol (as needed in women of 
non-childbearing potential only) 
• 
Serum or urine human chorionic gonadotropin (hCG) pregnancy test (as needed for 
women of childbearing potential) f 
• 
Serology (human immunodeficiency antibody [HIV], hepatitis B surface antigen 
[HBsAg], and hepatitis C virus antibody) 
• 
All study-required laboratory assessments will be performed by a central laboratory 
except the platelet count which is done by local laboratory 
• 
The results of each test must be entered into the electronic Case Report form  
(eCRF) 
a Platelet count testing will be performed by a local laboratory.  
b International Normalized Ratio (INR) to be done only at Baseline (Visit 1) and for PDILI. 
c Activated partial thromboplastin time (aPTT) and fibrinogen will be done at all visits which require safety 
laboratory assessments. 
d Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1.1 and Section 10.5, Appendix 5. All events of ALT 3x upper limit 
of normal (ULN) and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR >1.5, if INR 
measured, may indicate severe liver injury (possible Hy’s Law) and must be reported as a serious adverse event 
(SAE) (excluding studies of hepatic impairment or cirrhosis). 
e Includes total IgG, IgG subclasses, IgA, IgM, and IgE. Results of the IgG testing will be unblinded starting with 
the blood samples taken at Week 4 (Visit 5) in TP0004 in order maintain blind of the parent studies. 
f Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
Independent Review Board/Independent Ethics Committee. 
Investigators must document their review of each laboratory safety report. 
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10.3 
Appendix 3: Adverse events – definitions and procedures for 
recording, evaluating, follow-up, and reporting 
10.3.1 
Definition of AE 
Adverse Event (AE) Definition 
• An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of IMP, whether or not considered related to the IMP. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of IMP. 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from Baseline, considered clinically significant in the medical 
and scientific judgment of the investigator (ie, not related to progression of underlying 
disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after IMP administration even though it may have 
been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either IMP or a 
concomitant medication. Overdose per se will not be reported as an AE/serious AE (SAE) 
unless it is an intentional overdose taken with possible suicidal/self-harming intent. Such 
overdoses should be reported regardless of sequelae. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfil the definition of an AE or SAE. 
 
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Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the study participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the study participant’s 
condition. 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
10.3.2 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. Complications 
that occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
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e. 
Is a congenital anomaly/birth defect 
f. 
Important medical events: 
• Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered serious. 
• Examples of such events include, but are not limited to, potential Hy’s law, invasive or 
malignant cancers, intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
10.3.3 
Recording and Follow-up of AE and/or SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
• The investigator will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to UCB in lieu of completion of the UCB AE/SAE eCRF page. 
• There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, 
will be redacted on the copies of the medical records before submission to UCB. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
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Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories: 
• Mild: An event that is easily tolerated by the study participant, causing minimal discomfort 
and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe. 
• An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe (eg, a severe AE may 
be either serious or not serious, depending on whether these criteria are also met). 
The National Cancer Institute Common Terminology Criteria for Adverse Events 
(NCI-CTCAE) should be used as a supportive standardization instrument to evaluate AEs and 
SAEs but the final intensity grading by the investigator must be mild, moderate, or severe. 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between IMP and each occurrence 
of each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to IMP administration will be 
considered and investigated. 
• The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to UCB. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to UCB. 
• The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
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Follow-up of AEs and SAEs 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by UCB to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
• An AE should be followed until it has resolved, has a stable sequelae, the investigator 
determines that it is no longer clinically significant, the event is otherwise explained or the 
participant is lost to follow-up. This follow-up requirement applies to AEs, SAEs, and AEs 
of special interest. 
• If a study participant dies during participation in the study or during a recognized 
Follow-up Period, the investigator will provide UCB with a copy of any post-mortem 
findings including histopathology. 
• New or updated information will be recorded in the originally completed eCRF. 
• The investigator will submit any updated SAE data to UCB within 24 hours of receipt of 
the information. 
10.3.4 
Reporting of SAEs 
SAE Reporting to UCB via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to UCB will be the electronic data collection 
tool. 
• If the electronic system is unavailable for more than 24 hours, then the site will use the 
paper SAE data collection tool (see “SAE Reporting to UCB via Paper Case Report Form 
[CRF]” below). 
• The site will enter the SAE data into the electronic system as soon as it becomes available. 
• After the study is completed at a given site, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken off-
line, then the site can report this information on a paper SAE form (see next section). 
• Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING. 
 
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SAE Reporting to UCB via Paper CRF 
• Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to UCB; see SERIOUS ADVERSE EVENT REPORTING. 
• In rare circumstances and in the absence of facsimile equipment, notification by telephone 
is acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service. 
• Initial notification via telephone does not replace the need for the investigator to complete 
and sign the SAE CRF pages within the designated reporting time frames. 
• Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING. 
 
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10.4 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
− A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). However, in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient. 
− Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception Guidance 
Male participants 
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following during the Treatment Period and for at least 3 months after the 
final dose of study treatment: 
• Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent 
on a long term and persistent basis) and agree to remain abstinent 
• Agree to use a male condom when having penile-vaginal intercourse with a woman of 
childbearing potential who is not currently pregnant 
In addition, male participants must refrain from donating sperm for the duration of the study and 
for 3 months after the final dose of study medication. 
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Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration 
during the Treatment Period and for at least 3 months after the final dose of study treatment. 
Female participants 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in Table 10-2. 
Table 10-2: Highly effective contraceptive methodsa 
Highly Effective Contraceptive Methods That Are User Dependentb 
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen- and progesterone-containing) hormonal contraception associated with 
inhibition of ovulation 
• Oral 
• Intravaginal 
• Transdermal 
Progesterone only hormonal contraception associated with inhibition of ovulation 
• Oral 
• Injectable 
Highly Effective Methods That Are User Independent 
Implantable progesterone only hormonal contraception associated with inhibition of ovulation 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
Vasectomized partner 
Vasectomy is a highly effective contraception method provided that the vasectomized partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used. For Japan-specific 
requirements, see Appendix 7, Section 10.7. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study medication. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant. 
a In case of newly started contraception pills/IUDs, primary investigator should consider the correct timing of 
starting/applying such methods in relation to the menstrual cycle and the manufacturing instruction as when these 
newly started methods would become effective. 
b Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants in clinical studies. 
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Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive urine pregnancy test. 
• Additional urine pregnancy testing should be performed at time points specified in the 
Schedule of Activities (Section 1.3) and as required locally. 
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
• Pregnancy testing with a sensitivity of 25mIU/mL will be performed. A serum pregnancy test 
will be performed to confirm a positive urine pregnancy test. 
Male participants with partners who become pregnant 
• The investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This applies 
only to male participants who receive study medication.   
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within one working day of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-
up will be at least 12 months after the delivery date. Any termination of the pregnancy will 
be reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
Female participants who become pregnant 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study medication or be withdrawn from the study. 
• The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the sponsor within one working day of learning of a participant's 
pregnancy. The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the sponsor. Generally, the follow-up will be at least 
12 months after the delivery date. Any termination of pregnancy will be reported, regardless 
of fetal status (presence or absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such. Any post-study 
pregnancy-related SAE considered reasonably related to the study medication by the 
investigator will be reported to the sponsor as described in Section 8.2.5. While the 
investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting.
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10.5 
Appendix 5: Liver safety – suggested actions and follow-up 
assessments 
Study participants with PDILI must be assessed to determine if IMP must be discontinued. In 
addition, all concomitant medications and herbal supplements that are not medically necessary 
should also be discontinued. 
Investigators should attempt to obtain information on study participants in the case of IMP 
discontinuation to complete the final evaluation. 
Study participants with PDILI should not be withdrawn from the study until investigation and 
monitoring are complete. All results of these evaluations and observations, as well as the 
reason(s) for IMP discontinuation and/or participant withdrawal (if applicable), must be recorded 
in the source documents. The eCRF must document the primary reason for discontinuation of 
IMP. 
A specific monitoring plan must be agreed between the UCB Study Physician and the 
investigator for study participants who have ALT >5xULN. The monitoring plan should include 
any necessary follow-up assessments (until resolution of the abnormal laboratory values). 
Phase 3 or 4 liver chemistry stopping criteria are designed to assure participant safety and to 
evaluate liver event etiology (Table 10-3). 
Table 10-3: Phase 3 or 4 liver chemistry stopping criteria and follow-up 
assessments 
Liver Chemistry Stopping Criteria 
ALT absolute 
ALT 8xULN 
ALT increase 
ALT 5xULN but <8xULN persists for 2 weeks 
ALT 3xULN but <5xULN persists for 4 weeks 
Bilirubin a b 
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) 
INR b 
ALT 3xULN and International Normalized Ratio (INR) >1.5, if INR 
measured 
Cannot 
Monitor 
ALT 5xULN but <8xULN and cannot be monitored weekly for 2 weeks 
ALT 3xULN but <5xULN and cannot be monitored weekly for 4 weeks 
Symptomatic c 
ALT 3xULN associated with symptoms (new or worsening) believed to be 
related to liver injury or hypersensitivity 
Suggested Actions and Follow-up Assessments 
Actions 
Follow-up Assessments 
Immediately discontinue IMP. 
Report the event to UCB within 24 hours. 
Complete the liver event case report form 
(CRF), and complete a serious adverse event 
Viral hepatitis serology.d 
Obtain INR and recheck with each liver 
chemistry assessment until the transaminases 
values show downward trend. 
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(SAE) data collection tool if the event also 
met the criteria for an SAE. b 
Perform liver chemistry follow-up 
assessments. 
Monitor the participant until liver chemistry 
test abnormalities resolve, stabilize, or return 
to Baseline (see MONITORING). 
Do not restart/rechallenge participant with 
IMP unless allowed per protocol and UCB 
approval is granted. 
If restart/rechallenge not allowed per 
protocol or not granted, permanently 
discontinue IMP and continue participant in 
the study for any protocol specified follow-
up assessments. Consider the need for a 
toxicology screening. MONITORING: 
For bilirubin or INR criteria 
Repeat liver chemistry tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver event follow-up assessments 
within 24 hours. 
Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, 
stabilize, or return to Baseline. 
A specialist or hepatology consultation is 
recommended. 
For all other criteria 
Repeat liver chemistry tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver chemistry follow-up 
assessments within 24 to 72 hours. 
Monitor participants weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to Baseline. 
Only in those with underlying chronic hepatitis 
B at study entry (identified by positive 
hepatitis B surface antigen), quantitative 
hepatitis B deoxyribonucleic acid (DNA), and 
hepatitis delta antibody.e 
Obtain blood sample for pharmacokinetic (PK) 
analysis as soon as feasible after the most 
recent dose.f 
Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH). 
Fractionate bilirubin, if total bilirubin 
 2xULN. 
Obtain complete blood count with differential 
to assess eosinophilia. 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, 
on the adverse event (AE) report form. 
Record use of concomitant medications 
(including acetaminophen, herbal remedies, 
and other over-the-counter medications) on the 
concomitant medications CRF. 
Record alcohol use on the liver event alcohol 
intake CRF. 
Exclude pregnancy. 
For bilirubin or INR criteria 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total. 
immunoglobulin G (IgG) or gamma globulins. 
Serum acetaminophen concentration and 
serum acetaminophen adduct assay (where 
available) for assessing the potential 
acetaminophen contribution to liver injury. 
Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) and 
or liver biopsy to evaluate liver disease; 
complete Liver Imaging and/or Liver Biopsy 
CRFs. 
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue IMP if ALT ≥3xULN and bilirubin ≥2xULN. Additionally, if serum bilirubin 
fractionation testing is unavailable, record the absence/presence of detectable urinary bilirubin on dipstick, 
which is indicative of direct bilirubin elevations suggesting liver injury. 
b All events of ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin) or ALT ≥3xULN and INR >1.5 may 
indicate severe liver injury (possible ‘Hy’s Law’) and must be reported as an SAE (excluding studies of 
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hepatic impairment or cirrhosis). The INR measurement is not required and the stated threshold value will not 
apply to participants receiving anticoagulants. 
c New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash, or eosinophilia). 
d Includes: Hepatitis A immunoglobulin M (IgM) antibody; HBsAg and HBcAb; hepatitis C RNA; cytomegalovirus 
IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile antibody or monospot 
testing); and hepatitis E IgM antibody. 
e If hepatitis delta antibody assay cannot be performed, it can be replaced with a polymerase chain reaction (PCR) of 
hepatitis D RNA virus (where needed) (Le Gal et al, 2005). 
f Record the date/time of the PK blood sample draw and the date/time of the final dose of IMP prior to the PK blood 
sample draw on the eCRF. If the date or time of the final dose is unclear, provide the participant’s best 
approximation. If the date/time of the final dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the Laboratory Manual. 
Table 10-4: Phase 3-4 liver chemistry increased monitoring criteria with 
continued IMP 
Liver Chemistry Increased Monitoring Criteria 
Criteria 
Actions 
ALT 5xULN and <8xULN and 
bilirubin <2xULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 2 weeks. 
OR 
ALT 3xULN and <5xULN and 
bilirubin <2xULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 4 weeks. 
Notify the UCB medical monitor within 24 hours of 
learning of the abnormality to discuss participant 
safety. 
Participant can continue IMP. 
Participant must return weekly for repeat liver 
chemistry tests (ALT, AST, alkaline phosphatase, 
bilirubin) until the abnormalities resolve, stabilize, or 
return to Baseline. 
If at any time, the participant meets liver chemistry 
stopping criteria, proceed as described in 
Section 7.1.1. 
If ALT decreases from ALT 5xULN and <8xULN 
to ≥3xULN but <5xULN, continue to monitor liver 
chemistries weekly. 
If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor participants twice 
monthly until liver chemistry tests resolve, stabilize, 
or return to Baseline. 
REFERENCES 
Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Dény P, Gault E. Quantification of 
Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates Different Patterns 
of Virological Response to Interferon Therapy in Chronically Infected Patients. J Clin Microbiol. 
2005;43(5):2363–2369. 
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10.6 
Appendix 6: Medical device incidents – definition and 
procedures for recording, evaluating, follow-up, and reporting 
Not applicable. 
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10.7 
Appendix 7: Country-specific requirements 
Poland 
The Polish Health Authority’s and Clinical Trial Facilitation Group have made recommendations 
related to contraception and pregnancy testing in a clinical study with IMP where the human data 
for exposure at pregnancy and nonclinical reproductive toxicology data are not available. As a 
mitigation measure, pregnancy testing is to be implemented monthly up to 2 months after the 
final dose of IMP. A urine pregnancy test is added at 4 weeks after final IMP administration, 
thus it meets the above requirement. Based on the short half-life of IMP and because 
genotoxicity is not a class effect of the monoclonal antibodies, it is considered safe to reduce the 
duration of post-IMP administration requirement on contraception for female study participants 
of childbearing potential from 3 months to 2 months, with implementation of monthly pregnancy 
testing during this period. 
France 
Specific requirements for study participants in the France include: 
• In reference to Section 1.1 (Synopsis - Treatment Groups and Duration), the expected 
duration of the enrollment phase for an individual participant is defined as a visit window of 
up to +3 days from Week 25 of the parent study (TP0003 or TP0006). As study participants 
will enter this OLE study after completing participation in one of the parent studies, the 
overall timeline for this study is dependent on the enrollment trajectory of the parent studies. 
Anticipated timelines for completing enrollment of all participants in the parent studies is as 
follows: the last patient first visit of parent study is expected Jan 2024 with the last patient 
last dosing visit of parent study expected in Jul 2024. Based on these projections, the last 
patient first visit of TP0004 study is anticipated in Aug 2024, with the last patient last visit 
expected in Sep 2025. 
• In reference to Section 5.2 (Exclusion Criteria), 3 additional exclusion criteria: 
15. Study participant is deprived of their liberty by a judicial or administrative decision, or is 
receiving psychiatric care, and is admitted to a health or social institution, as defined in the 
French Public Health Code. 
16. Study participant is subject to legal protection or is unable to express consent, as defined in 
the French Public Health Code. 
17. Study participant is <18 years of age at the time of the Baseline Visit. 
Japan 
Specific requirements for study participants in Japan include: 
Locally approved devices are to be used during the study. If a pump and infusion set are used 
that are regarded in Japan as investigational devices, then additional adherence to specific 
reporting obligations will be required. All adverse device effects (ADEs), serious adverse device 
effects (SADEs), and medical device deficiency (including malfunction use error, and inadequate 
labeling) of these investigational devices shall be documented and reported by the investigator 
throughout the study and appropriately managed by the sponsor. 
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This reporting requirement is not applicable for locally approved devices for the purpose of sc 
infusions or other purposes in the course of this study, regardless if provided by the sponsor or 
not. 
• In reference to Section 6.4.1, the use of medicinal cannabidiols and medicinal marijuana are 
prohibited by law. 
• In reference to Section 10.4, Table 10-2 the following method has been added: 
“(eg, proper use of condom in combination with spermicide)” 
Furthermore, specific rules for repetition of an ADE and device deficiency should be followed 
by all study sites in Japan; this requirement is not applicable for locally approved devices, 
regardless if provided by the sponsor or not.  
For ADEs and/or device deficiencies that are not related to the natural course of the disease 
under study, an increase in the intensity of the original ADE, and/or device deficiency should 
lead to the repetition of the original ADE and/or device deficiency with the following guidelines: 
• The outcome date of the original ADE and/or device deficiency must be the same as the start 
date of the repeated ADE and/or device deficiency. 
• The outcome of the original ADE and/or device deficiency must be recorded as “worsening.” 
• The verbatim term for the repeated ADE and/or device deficiency must be the same as the 
verbatim term for the original ADE and/or device deficiency so that the repeated ADE and/or 
device deficiency is obviously a worsening of the original. 
As per local requirements in Japan, SAEs associated to an investigational device, and device 
deficiencies (eg, infusion pump product provided from sponsor) should be reported in 
accordance with the following.  
This requirement is not applicable for approved devices used in the course of the study, 
regardless if provided by the sponsor or not. 
Medical Device – Adverse events (ADEs, SAEs, and SADEs) and device 
deficiencies 
Medical devices are being provided for use in this study for subcutaneous infusions. In order to 
fulfill regulatory reporting obligations worldwide, the investigator is responsible for the detection 
and documentation of events meeting the definitions of incident or malfunction that occur during 
the study with such devices.  
Adverse events will be reported according to the ISO 14155:2011, while recognizing and 
following requirements including reporting timelines specified in other specific laws, 
regulations, directives, standards and/or guidelines as appropriate and as required by the 
countries in which the clinical investigation is conducted.  
NOTE: Events fulfilling the definition of an AE/SAE will also follow the processes outlined in 
Section 8.2.3 and Appendix 3 (Section 10.3) of the protocol. 
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Time period for detecting medical device deficiencies 
Medical device deficiency or malfunction of the device that results in a reportable event will be 
detected, documented, and reported during all periods of the study in which the medical device is 
used.  
If the investigator learns of any deficiency at any time after a participant has been discharged 
from the study, and such event(s) is considered reasonably related to a medical device provided 
for the study, the investigator will promptly notify the sponsor. 
Follow-up of medical device deficiencies 
Follow-up applies to all study participants, including those who discontinue study medication 
and/or the study. 
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
New or updated information will be recorded on the originally completed form with all changes 
signed and dated by the investigator. 
Prompt reporting of medical device deficiencies to sponsor 
Device deficiencies will be reported to the sponsor within 24 hours after the investigator 
determines that the event meets the protocol definition of a medical device deficiency. 
The Adverse Event and Device Deficiency Report Form will be sent to the sponsor by email. If 
email is unavailable, then fax should be utilized. 
The sponsor will be the contact for the receipt of device deficiency reports. 
Regulatory reporting requirements for medical device deficiencies 
The investigator will promptly report all device deficiencies occurring with any medical device 
provided for use in the study in order for the sponsor to fulfill the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety information relating to 
medical devices being used in clinical studies. 
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution) will comply with the applicable local regulatory requirements relating to the 
reporting of device deficiencies to the IRB/IEC. 
Medical Device AEs (ADEs, UADEs, SAEs, SADEs, and USADEs) and device 
deficiencies: Definition and procedures for recording, evaluating, follow-up, and 
reporting  
The definitions and procedures detailed in this appendix are in accordance with ISO 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements. 
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study.  
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Definition of AE and ADE 
AE and ADE Definition  
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally 
associated with the use of IMP, whether or not considered related to the IMP. NOTE: An AE 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP.  
• 
An adverse device effect (ADE) is defined as an adverse event related to the use of an 
investigational medical device. This definition includes events related to the investigational 
medical device or comparator and events related to the procedures involved except for events 
in users or other persons, which only include events related to investigational devices. This 
definition includes any adverse events resulting from insufficient or inadequate instructions for 
use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from intentional 
misuse of the investigational medical device. 
Definition of SAE, and SADE  
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is an AE that: 
a. Results in death  
b. Is life-threatening 
The term ‘life-threatening' in the definition of 'serious' refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician’s office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline 
is not considered an AE. 
d. Results in persistent disability/incapacity 
The term disability means a substantial disruption of a person's ability to conduct normal life 
functions. 
This definition is not intended to include experiences of relatively minor medical significance such 
as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, 
sprained ankle) which may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Important medical events 
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Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in the above definition. 
These events should usually be considered serious. 
Examples of such events include, but are not limited to, potential Hy’s law, invasive or malignant 
cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 
SADE definition 
• 
A SADE is defined as an adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
Definition of Device Deficiency 
Device Deficiency definition 
• 
A device deficiency is an inadequacy of an investigational medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. Device deficiencies include 
malfunctions, use errors, and inadequate labeling. 
Recording and Follow-Up of AE and/or SAE and Device Deficiencies 
AE, SAE and Device Deficiency Recording 
• 
When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator to review 
all documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE/device deficiency information in the 
participant’s medical records, in accordance with the investigator’s normal clinical practice and 
on the appropriate form of the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s medical records 
to UCB in lieu of completion of the AE/SAE/device deficiency CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to UCB. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
• 
For device deficiencies, it is very important that the investigator describes any corrective or 
remedial actions taken to prevent recurrence of the deficiency 
o A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency. This includes any amendment to the device design to prevent recurrence. 
The investigator should inform the sponsor for all reported device deficiencies.  
 
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Follow-up of AE/SAE/device deficiency 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by UCB to elucidate 
the nature and/or causality of the AE/SAE/device deficiency as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized follow-up period, 
the investigator will provide UCB with a copy of any post-mortem findings including 
histopathology.  
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The investigator will submit any updated SAE data to UCB within 24 hours of receipt of the 
information. 
Reporting of SAEs 
SAE Reporting to UCB via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to UCB will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data collection tool 
(see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then 
the site can report this information on a paper SAE form (see next section) or to UCB by 
telephone. 
• 
Contacts for SAE reporting can be found in this protocol. 
Reporting of SADEs 
SADE Reporting to UCB  
NOTE: There are additional reporting obligations for medical device deficiencies that are potentially 
related to SAEs that must fulfil the legal responsibility to notify appropriate regulatory authorities and 
other entities about certain safety information relating to medical devices being used in clinical studies.  
• 
Any device deficiency that is associated with an SAE must be reported to the sponsor within 
24 hours after the investigator determines that the event meets the definition of a device 
deficiency using the paper form provided by the sponsor. 
• 
The sponsor shall review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These shall be reported to the regulatory authorities 
and IRBs/IECs as required by national regulations. 
• 
Contacts for SAE reporting can be found in this protocol. 
 
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Reporting of AE and/or Device Deficiencies  
AE and/or Device Deficiencies Reporting to UCB  
NOTE: There are additional reporting obligations for medical device deficiencies that must fulfil the 
legal responsibility to notify appropriate regulatory authorities and other entities about certain safety 
information relating to medical devices being used in clinical studies.  
• 
Any AE and/or device deficiencies must be reported to the Sponsor within 24 hours after the 
Investigator determines that the event meets the definition of a device deficiency using the 
paper form provided by the Sponsor. 
• 
The sponsor shall review all device deficiencies and determine and document in writing 
whether they meet device reporting requirement.  
• 
Contacts for SAE reporting can be found in this protocol. 
10.7.1 
Countries where self-administration will be offered as an option 
Self-administration will be offered as an option to the following countries: 
• Austria 
• Belgium 
• Canada 
• France 
• Germany  
• Italy 
• Japan 
• Poland 
• Russian Federation 
• Spain 
• Ukraine 
• United Kingdom 
• United States 
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10.8 
Appendix 8: Rapid alert procedures 
Not applicable. 
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10.9 
Appendix 9: Abbreviations and trademarks 
ADA 
antidrug antibody 
ADE 
adverse device effect 
ADL 
activities of daily living 
AE 
adverse event 
AESM 
adverse event of special monitoring 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
anti-d 
anti-Rho 
AST 
aspartate aminotransferase 
BP 
blood pressure 
CDC 
Centers for Disease Control and Prevention 
CRF 
Case Report form 
CRO 
contract research organization 
CRP 
c-reactive protein  
ECG 
electrocardiogram 
eCRF 
electronic Case Report form 
eqv 
equivalent 
EOS 
End of Study 
EQ VAS 
EuroQoL visual analog scale 
EQ-5D-5L 
European Quality of Life-5 Dimension 5 Levels 
EW 
Early Withdrawal 
FcRn 
neonatal Fc receptor 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HCP 
healthcare professional 
HRQoL 
health-related quality of life 
HRT 
hormone replacement therapy 
IB 
Investigator's Brochure 
ICF 
Informed Consent form 
ICH 
International Council for Harmonisation 
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IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin  
IGRA 
interferon-gamma release assay 
IMP 
investigational medicinal product 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
ITP 
immune thrombocytopenia 
ITP-BAT 
ITP-specific Bleeding Assessment Tool 
ITP-PAQ 
ITP-Patient Assessment Questionnaire 
iv 
intravenous 
IVIg 
intravenous immunoglobulin 
K-PD 
kinetic-pharmacodynamic 
LLOQ 
lower limit of quantification 
LTB 
latent tuberculosis 
LTBI 
latent tuberculosis infection 
MAP 
managed access program 
MG 
myasthenia gravis 
NTMBI 
nontuberculous mycobacterial infection 
OLE 
open-label extension 
PD 
pharmacodynamic 
PDILI 
potential drug-induced liver injury 
PEX 
plasma exchange 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PK 
pharmacokinetic 
PRO 
patient-reported outcome 
Q2W 
every 2 weeks 
QoL 
quality of life 
QTc 
corrected QT interval 
QW 
every week 
RO 
Receptor Occupancy 
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SADE 
serious adverse device effects 
SAE 
serious adverse event 
SIAQ 
self-injection assessment questionnaire 
SAP 
Statistical Analysis Plan 
sc 
subcutaneous 
SF-36 
Short-Form 36-Item Health Survey 
SFU 
Safety Follow-Up 
SMOG 
Skin-Visible Mucosa-Internal Organs tool 
SS 
Safety Set 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TPO-RA 
thrombopoietin-receptor agonists 
UADE 
unanticipated adverse device effect  
USADE 
unanticipated serious adverse device effect 
ULN 
upper limit of normal 
VAS 
visual analog scale 
WHO 
World Health Organization 
WOCBP 
woman of childbearing potential 
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10.10 
Appendix 10: ITP-BAT 
Grading of bleeding symptoms at presentation and at each subsequent evaluation.1 
Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
SKIN 
 
 
 
 
 
Petechiae (does not 
include steroid–induced 
or senile purpura) 
 No 
 Less than or equal 
to 10 in a patient’s 
palm-sized area3 in the 
most affected body 
area4 
 Any number if 
reported by the patient 
 More than 10 in a 
patient’s palm-sized 
area or more than 5 in at 
least 2 patient’s palm-
sized areas located in at 
least 2 different body 
areas4, one above and 
one below the belt (in 
the most affected body 
areas) 4 
 More than 50, if 
scattered both above 
and below the belt 
 
Ecchymoses 
 None or up to 
2 in the same body 
area4, but smaller 
than a patient’s 
palm-sized area, if 
a) spontaneous or 
b) disproportionate 
to trauma/ 
constriction5 
 3 or more in the 
same body area4, but 
all smaller than a 
patient’s palm-sized 
area, if 
a) spontaneous or  
b) disproportionate to 
trauma/constriction5 
 At least 2 in two 
different body areas4, 
smaller than a patient’s 
palm-sized area, if 
a) spontaneous or  
b) disproportionate to 
trauma/constriction5 
 From 1 to 5 larger 
than a patient’s 
palm-sized area, if 
a) spontaneous or  
b) disproportionate to 
trauma/constriction5 
with or without smaller 
ones 
 More than 5 larger 
than a patient’s palm-
sized area, if 
a) spontaneous or  
b) disproportionate to 
trauma/ constriction5 
 
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Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
 Any number and 
size if reported by the 
patient 
Subcutaneous 
hematomas 
 No 
 1 smaller than a 
patient’s palm-sized 
area 
 Any number and 
size if reported by the 
patient 
 2 smaller than a 
patient’s palm-sized 
area, spontaneous  
 2 smaller than a 
patient’s palm-sized 
area, disproportionate to 
trauma5 
 More than 2 
smaller or at least 1 
larger than a patient’s 
palm-sized area, 
spontaneous  
 More than 2 
smaller or at least 1 
larger than a patient’s 
palm-sized area, 
disproportionate to 
trauma5 
 
Bleeding from minor 
wounds6 
 No 
 Lasting <5 min 
 Any episode if 
reported by the patient 
 Lasting >5 min or 
interfering with daily 
activities 
 Requiring 
protracted medical 
observation at the 
time of this visit  
 Medical report 
describing patient’s 
evaluation by a 
physician 
 
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Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
MUCOSAL 
 
 
 
 
 
Epistaxis7 
 No 
 Lasting <5 min 
 Any episode if 
reported by the patient 
 Lasting >5 min or 
interfering with daily 
activities 
 Packing or 
cauterization or 
in-hospital evaluation 
at the time of this visit 
 Medical report 
describing packing or 
cauterization or in-
hospital evaluation 
 RBC 
transfusion or 
Hb drop >2g/dL 
Oral cavity – gum 
bleeding7 
 No 
 Lasting <5 min 
 Any episode if 
reported by the patient 
 Lasting >5 min or 
interfering with daily 
activities 
 Requiring 
protracted medical 
observation at the 
time of this visit  
 Medical report 
describing patient’s 
evaluation by a 
physician 
 
Oral cavity – 
hemorrhagic bullae or 
blisters 
 No 
 Less than 3 
 Any number if 
reported by the patient 
 From 3 to 10 but no 
difficulty with 
mastication 
 More than 10 or 
more than 5 if 
difficulty with 
mastication 
 
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Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
Oral cavity - bleeding 
from bites to lips & 
tongue or after 
deciduous teeth loss 
 No 
 Lasting <5 min 
 Any episode if 
reported by the patient 
 Lasting >5 min or 
interfering with daily 
activities 
 Interventions to 
ensure hemostasis or 
in-hospital evaluation 
at the time of this visit 
 Medical report 
describing 
interventions to 
ensure hemostasis or 
in-hospital evaluation 
 
Subconjunctival 
hemorrhage  
(not due to conjunctival 
disease) 
 No 
 Petechiae/ 
hemorrhage partially 
involving one eye 
 Any episode if 
reported by the patient 
 Petechiae/ 
hemorrhage partially 
involving both eyes, or 
diffuse hemorrhage in 
one eye 
 Diffuse 
hemorrhage in both 
eyes 
 
ORGAN (and internal 
mucosae) 
 
 
 
 
 
Gastrointestinal 
bleeding not explained 
by visible mucosal 
bleeding or lesion: 
Hematemesis, 
Melena, 
Hematochezia, 
Rectorrhagia 
 No 
 Any episode if 
reported by the patient 
 Present at the visit  
 Described in a 
medical report  
 Requiring 
endoscopy8 or other 
therapeutic 
procedures or in-
hospital evaluation at 
the time of this visit 
 Medical report 
prescribing 
endoscopy8 or other 
therapeutic 
procedures or in-
hospital evaluation 
 RBC 
transfusion or 
Hb drop >2g/dL 
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Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
Lung bleeding 
Hemoptysis 
Tracheobronchial 
bleeding 
 No 
 Any episode if 
reported by the patient 
 Present at this visit 
 Described in a 
medical report 
 Requiring 
bronchoscopy8 or 
other therapeutic 
procedures or in-
hospital evaluation at 
the time of this visit 
 An equivalent 
episode if described 
in a medical report 
 RBC 
transfusion or 
Hb drop >2g/dL 
Hematuria 
 No 
 Any episode if 
reported by the patient 
 Microscopic (lab 
analysis) 
 Macroscopic  
 Described in a 
medical report 
 Macroscopic, and 
requiring cystoscopy8 
or other therapeutic 
procedures or in-
hospital evaluation at 
the time of this visit 
 An equivalent 
episode if described 
in a medical report 
 RBC 
transfusion or 
Hb drop >2g/dL 
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Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
Menorrhagia 
(compared to pre-ITP 
or to a phase of disease 
with normal platelet 
count)9 
 No 
 Doubling nr. of 
pads or tampons in last 
cycle compared to pre-
ITP or to a phase of 
disease with normal 
platelet count 
 Score >100 using 
PBAC in the last 
cycle, if normal score 
in pre-ITP cycles or in 
a phase of disease with 
normal platelet count 
 Changing pads more 
frequently than every 2 
hrs. or clot and flooding 
 Requiring combined 
treatment with 
antifibrinolytics and 
hormonal therapy or 
gynecological 
investigation (either at 
this visit or described in 
a medical report) 
 Acute 
menorrhagia requiring 
hospital admission or 
endometrial ablation 
(either at this visit or 
described in a medical 
report) 
 RBC 
transfusion or 
Hb drop >2g/dL 
Intramuscular 
hematomas 
(only if diagnosed by a 
physician with an 
objective method) 
 No 
 Post trauma, 
diagnosed at this visit, 
if judged 
disproportionate to 
trauma 
 An equivalent 
episode if described in 
a medical report 
 Spontaneous, 
diagnosed at this visit 
 An equivalent 
episode if described in a 
medical report 
 Spontaneous or 
post trauma (if judged 
disproportionate to 
trauma) diagnosed at 
this visit and 
requiring hospital 
admission or surgical 
intervention 
 An equivalent 
episode if described 
in a medical report 
 RBC 
transfusion or 
Hb drop >2g/dL 
Hemarthrosis 
(only if diagnosed by a 
physician with an 
objective method) 
 No  
 Post trauma, 
diagnosed at this visit, 
function conserved or 
minimally impaired, if 
judged 
 Spontaneous, 
diagnosed at this visit, 
function conserved or 
minimally impaired 
 Spontaneous or 
post trauma (if judged 
disproportionate to 
trauma), diagnosed at 
this visit and 
requiring 
 Spontaneous 
or post trauma 
(if judged 
disproportionate 
to trauma) 
diagnosed at this 
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Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
disproportionate to 
trauma 
 An equivalent 
episode if described in 
a medical report 
 An equivalent 
episode if described in a 
medical report 
immobilization or 
joint aspiration 
 An equivalent 
episode if described 
in a medical report 
visit and 
requiring 
surgical 
intervention 
 An 
equivalent 
episode if 
described in a 
medical report 
Ocular bleeding 
(only if diagnosed by a 
physician with an 
objective method) 
 No 
 
 Any post trauma 
vitreous or retinal 
hemorrhage involving 
one or both eyes with or 
without 
impaired/blurred vision 
present at this visit if 
judged disproportionate 
to trauma 
 An equivalent 
episode if described in a 
medical report 
 Spontaneous 
vitreous or retinal 
hemorrhage involving 
one or both eyes with 
impaired/blurred 
vision present at this 
visit 
 An equivalent 
episode if described 
in a medical report 
 Spontaneous 
vitreous or 
retinal 
hemorrhage with 
loss of vision in 
one or both eyes 
present at this 
visit 
 An 
equivalent 
episode if 
described in a 
medical report 
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Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
Intracranial bleeding10: 
intracerebral, 
intraventricular, 
subarachnoidal, 
subdural, extradural 
(only if diagnosed with 
an objective method at 
the visit or described in 
a medical report 
provided by the 
patient) 
 No 
 
 Any post trauma 
event requiring 
hospitalization 
 Any spontaneous 
event requiring 
hospitalization in 
presence of an 
underlying 
intracranial lesion 
 Any 
spontaneous 
event requiring 
hospitalization 
without an 
underlying 
intracranial 
lesion 
Other internal 
bleeding: 
hemoperitoneum 
hemopericardium 
hemothorax 
retroperitoneal bleeding 
hepatic and splenic 
peliosis with organ 
rupture 
retroorbital bleeding 
metrorrhagia 
etc. 
(only if diagnosed with 
an objective method at 
the visit or described in 
a medical report 
 No 
 
 
 Any event 
requiring 
hospitalization <48 
hrs. 
 Any event 
requiring 
hospitalization 
>48 hrs. or RBC 
transfusion or 
Hb drop >2g/dL 
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Table 10-5: ITP-Bleeding Assessment Tool 
Type of bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2 
 
0 
1 
2 
3 
4 
provided by the 
patient) 
Hb=hemoglobin; hrs=hours; ITP=immune thrombocytopenia; nr=number; PBAC= Pictorial Blood Loss Assessment Chart; RBC=red blood cell; SMOG=Skin-
Visible Mucosa-Internal Organs tool 
1 In case of study participants examined for the first time, all types of bleeding occurring at the visit and in the 15 days preceding the visit should be considered.  
2 Each type of bleeding should be graded based on the worst bleeding manifestation that occurred during each observation period or in the 15 days preceding the 
first visit. 
3 Study participant’s own palm size is commonly considered to be proportional to body surface area. Palm=the inner surface of the hand stretching between the 
distal crease of the wrist and the bases of the fingers (fingers surface excluded). 
4 Body areas include: face, neck, right and left upper limbs (considered separately), right and left lower limbs (considered separately), trunk, abdomen, and 
recumbent areas (for the ambulatory patient means the area below the knees).  
5 Bleedings considered proportionate to trauma/constriction on a clinical ground should not be reported for skin domain. 
6 Minor wound means superficial skin cuts (eg, by shaving razor, knife, or scissors). 
7 Epistaxis and gum bleeding are also reported in some normal study participants. Thus, a critical judgment is required in grading these manifestations; they 
should be reported only if judged more severe when compared with pre-ITP bleeding, if any. 
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8 Any endoscopic investigations should be considered for grading only if performed for therapeutic purpose and not solely for diagnostic purpose. 
9 In girls at menarche, grade 1 cannot be assigned, lacking comparison with previous cycles. 
10 Intracranial bleeding should always be reported, irrespective of its grade. For example, if a woman had S2 (subcutaneous hematoma) M2 (epistaxis) O3 
(menorrhagia) and an intracranial bleeding grade 2 (post trauma, requiring hospitalization), the SMOG index is S2M2O3 (intracranial 2). If the same 
participant also had intracranial bleeding grade 3, the SMOG index is S2M2O3 (intracranial 3). 
Note: Grading is based on physical examination at the time of the visit by the physician or expert nurse or on study participant’s history supplemented by 
available medical reports. Bleeding manifestations reported by the study participant but not visible at the time of data collection are graded 1. Grade 5 is 
assigned to fatal bleeding. 
Note: Illustrative examples are available on the website of the Hematology Project Foundation (http://itpbat.fondazioneematologia.it/). 
Note: To receive a grade >1, all nonovert skin and non-overt mucosal bleeding (petechiae, ecchymoses, subcutaneous hematomas, vescicles/bullae 
subconjunctival bleeding) should be visible at the time of visit for grading by the physician or expert nurse taking the history.  
Note: For bleeding from minor wounds and overt-mucosal bleeding (epistaxis, gum, bleeding from bites to lips & tongue or after deciduous teeth loss/extraction) 
and all organ bleeding, a medical record describing the symptom or indicating a specific intervention/prescription should be also taken into account for grading. 
Note: Requirement for ITP-specific treatments and anti-fibrinolytics (apart from menorrhagia) was not considered for grading, due to their subjective nature and 
their adoption not only to control actual bleeding but also to reduce the “risk” of impendent or future bleeding. 
 
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10.11 
Appendix 11: ITP-PAQ 
 
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10.12 
Appendix 12: SF-36 Form 
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10.13 
Appendix 13: FATIGUE-PRO Physical Fatigue Scale 
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10.14 
Appendix 14: EQ-5D-5L 
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10.15 
Appendix 15: PGI-S 
The following question asks you about your current overall ITP symptoms. 
Please check the box that best describes your current situation. 
 
How would you describe your ITP symptoms during the past week? 
 
None 
 
Mild 
 
Moderate 
 
Severe 
 
Very severe 
 
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10.16 
Appendix 16: PGI-C 
The following question asks you about your overall symptoms now compared to before starting 
treatment within this clinical study.  
Please check the box that best describes your current situation. 
 
How would you describe your current ITP symptoms compared to before you started 
treatment in this clinical study? 
 
Very much worse 
 
Much worse 
 
A little bit worse 
 
No change 
 
A little bit improved 
 
Much improved 
 
Very much improved 
 
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10.17 
Appendix 17: Headache Questionnaire 
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10.18 
Appendix 18: Tuberculosis assessment 
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10.19 
Appendix 19: Sampson Criteria Questionnaire 
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 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) 
Reduced BP after exposure to known allergen for that study participant (minutes to several 
hours): Systolic BP of less than 90mmHg or greater than 30% decrease from the study 
participant’s Baseline systolic BP value. 
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10.20 
Appendix 20: Management of headache 
Based on current available clinical data, headache is the most commonly reported adverse drug 
reaction in study participants treated with rozanolixizumab. Study participants should be well 
informed of this potential adverse drug reaction and should be instructed on how to manage it.  
Determination of the severity of headache will be consistent with National Cancer Institute 
Terminology Criteria for Adverse Events (CTCAE) version 5.0 (see Appendix 3, Section 10.3). 
Severe headache is defined as severe pain limiting self-care activities of daily living (ADL). 
Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, and 
taking medications.  
In the event of a headache the investigators should take the medical history of previous 
headaches, concomitant medication, and comorbidities (eg, asthma) into consideration.  
The Headache Questionnaire (Appendix 17, Section 10.17) should be administered daily by a 
health care professional via an interview with any study participant experiencing moderate, 
severe and/or serious headache until resolving or resolution (ie, if headache becomes nonserious, 
mild, or completely resolved, whichever comes first). If the severe or serious headache is 
initially reported at a home visit or during a telephone call, the study participant should be seen 
at the study site as soon as is practically possible for further investigations. Study participants 
should be monitored for signs and symptoms suggestive of central nervous system involvement 
and evaluated immediately if other causes (eg, meningitidis, intracranial bleeding) are suspected. 
Further neurological workup may be performed (if indicated) at the discretion of the investigator 
or the treating physician and may include a computed tomography scan, magnetic resonance 
imaging and/or a lumbar puncture for cerebral spinal fluid collection. In addition, samples for 
exploratory safety biomarkers should be collected for study participants experiencing severe 
headaches or serious headaches when possible. These investigations will be performed to further 
understand the mechanism of headaches in the study participants. 
Treatments must be permanently discontinued if a study participant has a serious headache (SAE 
of headache) that is considered related to the IMP in the opinion of the investigator. If a study 
participant experiences a severe AE of headache that is considered related to the IMP in the 
opinion of the investigator, the dose of IMP may be reduced or the treatment may be temporarily 
put on hold. If the treatment has been put on hold and if deemed appropriate by the investigator 
and agreed upon by the study participant and the sponsor, the study treatment can resume upon 
the resolution of the severe headache event, at the previous dose or at a lower dose. The benefit 
and risk of the treatment should be carefully considered prior to reinitiating the IMP. If a study 
participant experiences a second episode of treatment-related severe headache in the opinion of 
the investigator, the treatment can only be continued upon agreement with the sponsor, 
investigator, and study participant taking benefit and risk into consideration. If the benefit-risk 
balance is not acceptable, then the participant must discontinue the IMP. However, if a 
participant experiences >2 severe headaches that is considered related to the IMP in the opinion 
of the investigator, the treatment must be permanently discontinued.  
Dosing modifications are allowed if judged necessary by the investigator from 
 to 
 or from
to 
 based on specific volume reduction per protocol 
guidance, provided the treatment is effective as evidenced by relevant efficacy measurements 
(eg, platelet count ≥30×109/L).  
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Headaches will be treated as clinically indicated according to national guidelines. It is 
recommended that the study participant has an analgesic available in case of headache with the 
instruction for frequency and dosage provided by a health care professional. The analgesic can 
be started at the early onset of headache. Study participants experiencing any treatment-related 
headache will be followed until resolution of the event.   
Prophylactic treatment of headaches may be permitted for study participants who have 
experienced previous episodes of treatment-related moderate or severe headache after discussion 
with the Medical Monitor. The benefit and risk of continuing treatment with IMP and chronic 
prophylactic treatment with analgesics must be carefully evaluated by the investigator. 
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10.21 
Appendix 21: Management of diarrhea 
Severe (Grade 3) diarrhea is defined as an increase of ≥7 stools per day or hospitalization for 
management of diarrhea or limiting self-care ADL. Determination of the severity of diarrhea will 
be consistent with CTCAE version 5.0 (see Appendix 3, Section 10.3, for further details). 
Diarrhea will be treated as clinically indicated according to the local guidelines. 
Stool samples may be collected for stool analysis to rule out infection for study participants 
reporting severe diarrhea. Stool sampling will be done as clinically indicated in the opinion of 
the investigator and assessed per local guidance. In addition, collection of blood samples for 
assessment of exploratory safety biomarkers is required for study participants with severe GI 
disturbances including diarrhea.  
In study participants experiencing severe treatment-related diarrhea, dosing modifications are 
allowed, if judged necessary by the investigator from 
to 
or from 
 to 
 based on specific volume reduction per protocol guidance, provided the 
treatment is effective as evidenced by relevant efficacy measurements (eg, platelet count 
≥30×109/L). 
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10.22 
Appendix 22: Management of infections and 
hypogammaglobulinemia 
Study participants who have the signs or symptoms of any infection should be monitored closely 
and managed according to local guidelines. This may include tests for specific organisms if 
clinically indicated. 
If a study participant has a significant infective episode including but not limited 
to bacteremia/sepsis, infectious meningitis, septic arthritis, osteomyelitis, complicated 
pneumonia, or visceral abscess which may or may not result in hospitalization, they MUST 
discontinue IMP, perform the EW Visit, enter the SFU Period and complete the EOS Visit. This 
list is not intended to be all inclusive and the investigator is expected to apply his/her judgment 
on continuing IMP based on the clinical situation at hand. 
To maintain the study integrity, study site personnel, the UCB and CRO study teams will remain 
blinded to IgG levels until Week 4 (Visit 5). However, to ensure study participants’ safety, serum 
IgG level will be monitored by unblinded Medical Monitors external to UCB until Week 4 
(Visit 5) and by the blinded Medical Monitors starting with the blood samples taken at Week 4 
(Visit 5). In case the serum IgG level decreases <1g/L, as described below and in Table 10-7, the 
unblinded/blinded Medical Monitors will inform the investigator.  
The most recently available IgG value is the trigger for discussions between the 
unblinded/blinded Medical Monitors and the investigator and for any decisions on 
changing/skipping the dose of IMP. All discussions and decisions related to the benefit-risk of 
dose change/skip are to be based on a holistic approach of the study participant’s status, 
including platelet response (eg, study participant’s ITP history, stability of the current response, 
past and current platelet counts), current signs and symptoms of nonserious/serious infection, 
potential risk of acquiring a nonserious/serious infection in the foreseeable future and are at the 
sole discretion of the investigator.  
The investigator must document the respective benefit-risk assessments and decisions in the 
study participant’s source documents.  
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Table 10-7: Management of infections and hypogammaglobulinemia 
IgG value 
Actions  
Outcome 
IgG <1g/La 
Unblinded medical monitor 
informs the investigator 
Investigator decides to either: 
• maintain the dose 
• reduce the dose 
• skip dose  
based on the study 
participant’s status regarding 
platelets response, signs & 
symptoms of nonserious/ 
serious infection, potential 
risk of acquiring a 
nonserious/serious infection 
AE=adverse event; eCRF=electronic case report form 
a Events of hypogammaglobulinemia must not be captured as an AE in the eCRF, to protect the blind.  
Dose adjustments/dose skipped  
The dose of IMP can be reduced from 
equivalent (eqv.) to 
 eqv., from
 
eqv. to 
 (approx. 
), or directly from 
eqv. to 
 (approximately 
), as needed.  
The IgG would be expected to return to values ≥1g/L in up to 3-4 weeks (after a dose 
decrease/skip). The level of IgG recovery will depend on the IgG observed value that triggered 
the intervention and the intra-study participants variability, so that the IgG level may not 
immediately increase, and a delayed effect could be expected.  
The study participant will need to be reassessed on an ongoing basis regarding platelet response 
and risk of infection until the serum IgG returns to values ≥1g/L. The dose may be further 
decreased, or it can be skipped, if needed. 
In case a dose is skipped, IMP administration may be restarted at a lower dose compared to the 
previous dose in order to decrease the likelihood of any further repeated reduction in the IgG 
level <1g/L.  
Ad hoc assessments (eg, additional weekly IgG samples) may be performed to monitor recovery 
of IgG levels.  
Splenectomized Study Participants 
Splenectomised study participants are at a higher risk of infections, especially of overwhelming 
post-splenectomy infections. Irrespective of the IgG level, in case a splenectomised study 
participant develops a (persistent or re-occurring) nonserious infection, the dose of IMP can be 
reduced, or the IMP treatment may be temporarily stopped, when appropriate, at the 
investigator’s discretion. The IMP treatment may be resumed at the previous dose after the 
resolution of the event. The investigator may also reach out to the unblinded/blinded Medical 
Monitors, as needed.  
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Local guidelines regarding antibiotic prophylaxis in splenectomised study participants should be 
followed. Splenectomised study participants should have a prophylactic antibiotic available, 
unless they are already taking an antibiotic as per local guidance.  
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10.23 
Appendix 23: Management of infusion-related reactions or 
hypersensitivity reactions 
Study participants must be closely monitored for reactions during and after the IMP 
administration period. Standard precautions must be taken for the study participants with regard 
to potential infusion related reactions. Suggested management guidelines for infusion-related 
reactions and anaphylaxis at the study site are provided in Table 10-8. Definitions of the severity 
of the relevant events will be consistent with CTCAE version 5.0 (see Appendix 3, Section 10.3). 
Table 10-8: Suggested management guidelines for infusion reactions 
Type of reaction 
Suggested action 
Acute – Mild 
Grade 1 
Monitor vital signs every 10 min. 
If the reaction worsens to Grade 2, follow the instructions below.   
Acute – Moderate 
Grade 2 
Interrupt/hold infusion temporarily to further assess and initiate 
treatment if necessary.  
Consider the use of iv fluid and antihistamine iv or im. 
Consider administering paracetamol or NSAIDs. 
Monitor vital signs initially every 5 min. 
If the reaction improves and upon further assessment it is clear that the 
event is not an anaphylaxis, restart the infusion cautiously. Continue to 
monitor vital signs every 5 min. 
If reaction recurs or worsens to Grade 3, discontinue infusion. 
Acute – Severe 
Grade 3 or 
anaphylaxis 
Discontinue IMP infusion permanently. 
Alert crash team. 
Maintain airway; ensure oxygen is available. 
Administer: 
− Antihistamine iv/im, corticosteroids iv, epinephrine im, and iv 
fluids as appropriate. 
− Monitor vital signs every 2 min. 
− Hospitalize, if condition not improving or worsens. 
− Monitor study participant until symptoms resolve. 
CTCAE=Common Terminology Criteria for Adverse Events; im=intramuscular; IMP=investigational medicinal 
product; iv=intravenous(ly); NSAIDs=Nonsteroidal anti-inflammatory drugs 
Note: Management criteria were adapted from the CTCAE v5.0 (National Cancer Institute, 2017). 
In case of suspected anaphylaxis, the Sampson Criteria (Sampson et al, 2006) should be accessed 
and Appendix 19 (Section 10.19, Sampson Criteria Questionnaire) should be completed. The 
infusion must be discontinued immediately, and emergency resuscitation measures implemented. 
In study participants experiencing an infusion-related reaction or anaphylaxis, blood samples will 
be collected as soon as possible, while the event is ongoing, to investigate the nature of the 
reaction as per Schedule of Activities (Section 1.3). 
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Samples for serum complement s(C3, C4), plasma complements (C3a, C5a) should be collected 
as specified in the Schedule of Activities (Section 1.3). Additional tests such as IgE levels, 
tryptase may be performed when there is a suspicion of Type I or III hypersensitivity reaction. 
The results of all monitoring, including laboratory testing, should be made available to the study 
site and sponsor. 
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10.24 
Appendix 24: SIAQ (infusion version) 
PRE-SIAQ (Infusion version):  
 
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POST-SIAQ (Infusion version):  
 
 
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10.25 
Appendix 25: Protocol Amendment History 
Amendment 3 (09 Dec 2021) 
Overall Rationale for the Amendment 
The primary reason for this protocol amendment is to correct errors in Table 1-1 Schedule of 
Assessment at Weeks 19, 23, 27 and 51.  
Additional updates were incorporated to provide further clarity on the protocol or to correct 
errors. 
This amendment is considered to be non-substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European 
Union. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis, Objectives 
and Endpoints 
3 Objectives and endpoints 
Footnote “a” was added to the 
endpoints referring to “Baseline”. 
Updated for consistency.  
1.1 Synopsis, Objectives 
and Endpoints 
3 Objectives and endpoints 
The following secondary objective 
and endpoint were removed:  
• 
To assess the 
pharmacodynamic (PD) effect 
of rozanolixizumab  
• 
Total serum IgG (absolute 
value) and change from 
Baselinea (absolute value and 
percentage) in serum IgG and 
in serum IgG subclass 
concentration at each scheduled 
assessment   
To remove duplication as they will 
be assessed as an exploratory 
objective and endpoint. 
1.1 Synopsis, Overall 
design 
 
4.1 Overall design 
The sentence “In case of a late 
rollover, platelet counts will need 
to be remeasured.” was added.  
The sentence was deleted in error 
in Protocol Amendment 2.  
1.3 Schedule of activities, 
Table 1-1 Schedule of 
activities 
The following assessments were 
added to Weeks 19, 23, 27 and 51: 
Platelet count, vital signs, recording 
of AEs (including hospitalizations), 
serum complements (C3 and C4) 
and plasma complements (C3a and 
C5a), blood collection for 
exploratory biomarker analysis, 
ITP bleeding scale and headache 
questionnaire.  
Updated for consistency and to 
correct errors.  
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Section # and Name 
Description of Change 
Brief Rationale 
Assessments for pre-SIAQ and 
post-SIAQ were added at all dosing 
visits starting at Week 7.  
8.1.5.1 Tuberculosis 
assessment 
A new subsection for monitoring 
for TB during the study was added.  
Added for consistency across ITP 
protocols.  
Amendment 2 (03 Dec 2021) 
Overall Rationale for the Amendment 
The primary reason for this protocol amendment was the recommendation of the external 
Independent Data Monitoring Committee (IDMC) to modify the dosing regimen of the study. 
Additional updates were incorporated to provide further clarity on the protocol or to correct 
errors. 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Section # and Name 
Description of Change 
Brief Rationale 
Global 
IMP dosing 
 was 
updated to
.  
 
Updated based on the feedback 
from the IDMC recommending the 
option to increase the frequency in 
dosing, to reduce the potential 
risks associated with low platelet 
counts. 
Global 
Exploratory dosing was removed.  
Reference to maintenance dosing 
was removed. 
 
Updated based on the feedback 
from the IDMC recommending the 
option to increase the frequency in 
dosing, to reduce the potential 
risks associated with low platelet 
counts. Therefore, the exploratory 
arm intended to evaluate wider 
dosing intervals was removed as 
the scientific value is limited. 
Global 
54-week treatment period was 
updated to 52-week treatment 
period. 
Updated to provide clarity and 
consistency with remainder of the 
protocol. 
1.1 Synopsis 
Rationale 
Reference to the starting dose of 
fixed dose equivalent of
 
was removed. 
Deleted as the 
 equivalent 
starting dose is no longer applied 
in the parent studies TP0003 and 
TP0006.  
1.1 Synopsis, Objectives 
and Endpoints 
3 Objectives and endpoints 
 
Objectives corresponding to the 
exploratory dosing were removed. 
Reference to maintenance dosing 
was removed.  
 
 
Updated to provide consistency 
within the protocol due to the 
removal of the exploratory arm. 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Objectives were reworded from 
“…starting after the second dose of 
rozanolixizumab (Week 4)” to 
“…starting at Week 4.” 
Updated to reflect the changes in 
the dosing frequency. Reference to 
the "second dose" was deleted and 
reference is only made to Week 4. 
1.1 Synopsis, Objectives 
and endpoints 
 
3 Objectives and endpoints 
 
The other safety endpoints was 
updated to delete “α globulin and β 
globulin.” 
The other safety endpoint: 
“Change from Baseline in 
cytokines during the study (for 
study participants experiencing 
infusion reactions or 
hypersensitivity reactions)” was 
deleted. 
The endpoint was removed to 
decrease study complexity, as 
scientific value is limited. 
 
The endpoint was removed as the 
analysis of cytokines is not 
required in the ITP protocols as 
samples have been collected in 
other rozanolixizumab studies and 
no additional information is 
expected from the ITP population. 
1.1 Synopsis, Objectives 
and endpoints 
 
3 Objectives and endpoints 
The following PD secondary 
endpoint was updated as follows: 
“Minimum value in total serum 
IgG and maximum decrease from 
Baseline in total serum IgG 
concentration” was changed to 
“Total serum IgG (absolute value) 
and change from Baseline (absolute 
value and percentage) in serum IgG 
and in serum IgG subclass 
concentration at each scheduled 
assessment” 
Updated as this variable will be 
followed at every scheduled visit 
rather than only reporting the 
lowest value across the duration of 
the study. 
1.1 Synopsis, Objectives 
and endpoints 
 
3 Objectives and endpoints 
 
The following exploratory PD 
endpoints were updated as follows:  
“Minimum value in total serum 
IgG and maximum decrease from 
Baseline in total serum IgG 
concentration” was deleted. 
 
 
 
“Change from Baseline in serum 
IgG and in serum IgG subclass 
concentration over time” was 
updated to “Total serum IgG 
(absolute value) and change from 
Baseline (absolute value and 
percentage) in serum IgG and in 
serum IgG subclass concentration 
at each scheduled assessment.” 
“Change from Baseline in serum 
immunoglobulin concentrations 
 
 
Deleted as this variable will be 
followed at every scheduled visit 
rather than only reporting the 
lowest value across the duration of 
the study. 
 
 
Endpoint was amended to provide 
further details of the endpoint and 
to add clarity. 
 
 
 
 
 
 
Endpoint was amended to provide 
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Section # and Name 
Description of Change 
Brief Rationale 
(IgA, IgE, IgM)” was updated to 
“Absolute value and change from 
Baseline (absolute value and 
percentage) in serum 
immunoglobulin concentrations 
(IgA, IgE, IgM) at each scheduled 
assessment.” 
“Change from Baseline in ITP-
specific autoantibodies in serum” 
was deleted. 
further details of the endpoint and 
to add clarity. 
 
 
 
 
 
 
 
The endpoint was deleted as the 
results of the analysis will not be 
part of the CSR of this study and 
will be described in a separate 
report. 
1.1 Synopsis, Objectives 
and endpoints 
 
3 Objectives and endpoints 
The objective “To evaluate the 
effects of rozanolixizumab on 
exploratory biomarkers” and 
associated endpoints were 
removed.  
Objective and endpoint were 
removed as the exploratory 
biomarker samples are taken for 
future analysis, with no predefined 
analysis objective and endpoints 
1.1 Synopsis 
Overall design 
 
4.1 Overall design 
 
IMP dosing 
 was 
updated to 
 dosing.  
Rozanolixizumab dose 
administration was updated from 
Week 3, Visit 5 to Week 2, Visit 3. 
Updated upon recommendation of 
the IDMC   
 
Updated to reflect the dosing 
frequency change from 
 
to 
dosing. 
 
1.1 Synopsis, Overall 
design 
 
4.1 Overall design 
 
The visit window upon rollover 
from TP0003 or TP0006 into 
TP0004, has been updated from 1 
week to 3 days.  
The requirement for a SFU visit in 
between or platelet count 
measurement in case of late 
rollover, has been removed.  
The wording on rozanolixizumab 
infusion was updated. 
The timepoints for observation 
after the end of infusion were 
updated.  
Updated for consistency with the 
 dosing regimen. 
1.1 Synopsis, Overall 
design 
 
4.1 Overall design 
The following paragraph was 
added: “Based on feedback from 
the IDMC, 
 dosing was 
implemented in protocol 
amendment 2. Study participants 
being treated with the 
 
dosing regimen will switch to the 
To clarify the dosing for existing 
study participants receiving 
 dosing 
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Section # and Name 
Description of Change 
Brief Rationale 
 dosing regimen once 
protocol amendment 2 is approved 
at the respective study site.” 
1.1 Synopsis 
Number of study 
participants 
Reference to the interim analysis 
was removed.  
To provide consistency with the 
feeder study protocols. The interim 
analysis in the feeder studies was 
removed.  
1.1 Synopsis 
Treatment groups and 
duration  
 
4.1 Overall design 
The total maximum study duration 
per study participants was updated 
to 59 weeks. 
To provide consistency within the 
protocol due to the change in 
dosing frequency. 
1.2 Schema 
Figure 1-1 TP0004 study 
schematic  
IMP dosing 
 was 
updated to 
 dosing.  
Reference to maintenance dosing 
was removed and changed to 
“treatment period.” 
The treatment period was corrected 
to 52 weeks.  
Week 55 was updated to Week 53. 
The Safety Follow-up Period was 
updated to Week 60.  
The total maximum study duration 
per study participants was updated 
to 59 weeks. 
To provide consistency within the 
protocol due to the change in 
dosing frequency and the removal 
of the exploratory arm.  
1.3 Schedule of Activities  
Table 1-1 Schedule of 
activities  
IMP dosing 
 was 
updated to 
 dosing. IRT 
contacts were updated accordingly. 
Columns related to home visits 
have been grayed out. 
Notes were added to clarify white 
columns are site visits and gray 
columns are optional home visits. 
Additional text was added to state 
“Home IMP administration and 
assessments are optional and can be 
conducted (if approved by 
regulatory agencies) at the sites as 
deemed necessary by site personnel 
and/or the study participant” 
The safety follow-up period was 
amended from W61, Day 420 to 
W60, Day 414. 
Updated to provide consistency 
within the protocol due to the 
change in dosing frequency, last 
dose being at Week 52 and the 
removal of the exploratory arm.  
 
Updated to harmonize the 
assessments and visits with the 
change in dosing regimen.  
 
 
 
 
 
 
 
 
 
 
The visit at Day 5 was removed 
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Section # and Name 
Description of Change 
Brief Rationale 
A +2 day time window for Week 1, 
Day 3 was added.  
A new footnote “a” was added: 
“The allowed time window for 
assessments is ±5 mins for 
assessments <30 mins and ±15 
mins for assessments >30 mins.” 
Footnote a now b: was updated to 
clarify that home visits, if 
applicable are displayed in the grey 
columns. The following sentence 
was removed: “If applicable, home 
administration of IMP is to be 
conducted unless not approved by 
regulatory agencies.” 
Footnote f now g:  was updated 
from “50 to 200×109/L” to “50 to 
150×109/L and no dose change.” 
Footnote g now h: visit window for 
rollover from TP0003 or TP0006 
was updated to +3 days. 
A new footnote “i” was added: 
“Platelet counts will be taken at the 
indicated home visits; however, the 
IMP dose will be based on the 
previous 4 platelet counts (must be 
stable between 50 to 150×109/L 
and no dose change). If criteria are 
not met, the visit must be 
conducted on site.” 
Footnote h now j: was updated to 
remove triplicate and three ECGs 
and the timepoints for ECG.  
Footnote j now k: vital sign 
assessment timepoints were 
updated. Footnote p now q: relating 
to onsite observation was updated 
accordingly.  
A new footnote “p” was added: 
“Prior to dosing, management of 
infections and 
hypogammaglobulinemia must be 
considered as per Appendix 22, 
Section 10.22.” 
Footnote q relating to the 
Exploratory Treatment Arm was 
deleted.  
therefore the Visit at Day 3 was 
given a visit window. 
 
To clarify the time window for 
assessments.  
 
 
 
Updated for clarity.  
 
 
 
 
 
 
 
Updated for consistency across 
other sections of the protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Updated for clarity.  
 
 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Footnote u now s: was updated to 
remove the 4 hour postdose 
assessments at Baseline and Week 
33.  
Footnote “t” relating to 2 to 5 days 
postdose PK and ADA samples 
was deleted.  
Footnote “u” was updated to add 
“and/or serious.”  
A new footnote “v” was added: If 
total IgG levels are <1g/L, ad hoc 
assessments (eg, additional IgG 
samples) may be performed to 
monitor recovery of IgG levels. See 
Section 10.22.  
Footnote aa now z:  was updated as 
follows: This assessment is 
applicable only to participants 
experiencing moderate, severe 
and/or serious headache (see 
Section 10.20), and will be 
performed daily until resolution (ie, 
if headache becomes mild, normal 
collection of AEs should apply). 
This assessment can also be done 
remotely eg, via phone interview. 
The IGRA TB test and chest x-ray 
were deleted.  
 
 
The 4 hour postdose sample is not 
required.  
 
 
These samples are not required. 
 
Updated for consistency across 
other sections of the protocol.  
 
 
 
 
 
 
 
Updated for consistency with 
Section 10.20. 
 
 
 
 
 
 
 
 
 
Updated for consistency with 
Section 8.1.5 
Table 1-2 Schedule of 
activities – exploratory 
treatment arm (Weeks 25 
to 41) 
Table 1-2 was deleted.  
Updated to provide consistency 
within the protocol due to the 
removal of the exploratory arm.   
2.2. Background  
The background was updated to 
state the removal of the starting 
dose from feeder studies TP0003 
and TP0006. 
CIDP01 was added to the list of 
completed studies.  
 
Brief details about CIDP01 and 
CIDP04 were added. 
A note was added that in 
TP0003/TP0006 protocol 
amendment 3, the starting fixed 
dose equivalent to 
 sc was 
Updated for consistency with the 
change in dosing regimen, and 
with relevant completed or 
ongoing study information. 
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Section # and Name 
Description of Change 
Brief Rationale 
removed due to the change to 
weekly dosing. 
2.3 Benefit/risk assessment  The following cross reference was 
corrected from Section 6.5.1 to 
Section 8.2.9: “If any AEs were to 
occur, they should be handled as 
described in (Section 8.2.9) with 
causality assessment provided for 
both IMP and vaccine.” 
Cross reference was corrected.  
Table 4-1 TP0004 dose 
levels and weight tiers of 
IMP 
The table title was updated from 
‘rozanolixizumab’ to ‘IMP’. 
 
Updated to provide consistency 
within the protocol.  
Table 4-2 Dose 
adjustments of 
rozanolixizumab for 
maintenance treatment arm 
 
Figure 4-1 Dose 
adjustments of 
rozanolixizumab 
Additional instructions were added 
for platelet counts of <10×109/L 
and between ≥30×109/L to 
<50×109/L. 
Updated to provide further clarity 
on when rescue medication is to be 
used.  
Table 4-2 Dose 
adjustments of 
rozanolixizumab for 
maintenance treatment arm 
 
Figure 4-1 Dose 
adjustments of 
rozanolixizumab 
A clarification was added that 
rescue therapy is recommended 
when platelet count reaches 
<30×109/L. An additional row/box 
was added to clarify that platelet 
count <10×109/L instructions 
would be to administer rescue 
therapy. 
The text regarding interindividual 
variable platelet response 
previously in the section body was 
included as footnote ‘b’ to the 
table. 
Updated for clarity 
4.1 Overall design 
Vital signs measurement time 
points for all visits were updated 
and clarified. 
Updated for consistency with the 
change in dosing regimen. 
4.1 Overall design, Table 
4-2, Figure 4-1 
The following text was updated: 
Platelet counts of <10×109/L rescue 
therapy is highly recommended.  
 
Platelet counts of ≥10×109/L to 
<30×109/L (on at least two 
consecutive visits) rescue therapy is 
recommended.  
 
Updated to permit reduction in 
dose earlier in the event of a 
platelet increase given the change 
to a 
 dosing regimen.  
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Brief Rationale 
≥30×109/L to <50×109/L dose level 
can be increased unless the study 
participant is on a maintenance 
dose of 
.  
 
Platelet count of ≥50×109/L to 
≤200×109/L was updated to 
≥50×109/L to 150×109/L.  
 
Platelet count of >200×109/L to 
<400 x109/L was updated to 
150×109/L to <400 x109/L. 
 
For platelet counts of ≥400×109/L, 
instructions were updated to “Once 
the platelet count is ≤150×109/L, 
reinitiate treatment decreased by 
one dose level.” 
 
The text regarding interindividual 
variable platelet response was 
moved as table footnote b. 
4.3 Justification for dose  
A more frequent dosing regimen of 
 equivalent once per week 
is introduced in TP0003/TP0006 
and the  OLE study.  
The 
 equivalent starting 
dose in TP0003/6 is removed from 
the protocol. 
Updated to follow the advice of the 
external IDMC on introducing a 
more frequent dosing regimen to 
reduce the potential risks of low 
platelet counts. 
5.1 Inclusion criteria 
Criterion #1a, now 1b, was updated 
to state Visit 27. 
Updated as per updated visit 
numbering in studies 
TP0003/TP0006.  
5.1 Inclusion criteria  
Inclusion criteria #3 and #4 were 
removed.   
Inclusion criteria 3 and 4 were 
deleted as the criteria are not 
related to eligibility. Inclusion 
criterion 3: Highest permitted 
concomitant treatments are listed 
in table 6-2 and a stable dose is not 
required as an inclusion criterion 
Inclusion criterion 4: Depending 
on the IgG level, the participant 
should be dosed in accordance to 
Appendix 22 and IgG levels are 
not an inclusion criterion. 
5.1 Inclusion criteria 
Inclusion criterion #5, now 5a, was 
updated to correct “or” to “and” 
The sentence was corrected.  
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Section # and Name 
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Brief Rationale 
“as confirmed by a negative 
pregnancy test and not planning to 
get pregnant” 
5.2 Exclusion criteria 
Exclusion criterion #6a, now 6b, 
was updated to remove the bullet 
point relating to ALT, AST, or 
ALP results up to 25% above the 
exclusion limit may be repeated 
once for confirmation. 
Updated for providing additional 
clarity to this exclusion criterion. 
 
5.2 Exclusion criteria 
Exclusion criterion 12 was 
removed. 
No longer required as Baseline 
values are taken from 
TP0003/TP0006.  
6 Study treatments  
Table 6-1 Treatments 
administered  
Exploratory dosing was removed.  
IMP dosing 
 was 
updated to 
 dosing. 
Dosing instructions were updated.  
Updated to provide consistency 
within the protocol.   
6 Study treatments  
Table 6-1 Treatments 
administered 
Dosing instructions: “and Week 53 
measurement” was removed.  
Removed as the Week 53 body 
weight measurement is not used 
for the dose calculation.  
6.2 Measures to minimize 
bias: randomization  
Description of the Exploratory  
Arm was removed.  
Updated to provide consistency 
within the protocol.  
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies) 
An additional paragraph regarding 
the management of the concomitant 
ITP treatment of the study 
participants rolling over from 
TP0003/TP0006 to TP0004.  
To clarify the management of the 
concomitant ITP treatment of the 
study participants rolling over 
from TP0003/TP0006 to TP0004. 
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies), Table 6-2 
6.4.3.1 Rescue therapy not 
leading to discontinuation 
Permitted oral corticosteroids dose 
was increased to 20mg/day. 
Allowed dose of oral 
corticosteroids was increased to a 
maximum of 20mg/day for more 
flexibility in the managing the 
concomitant ITP treatment.  
6.4.3.2 Rescue therapy 
leading to discontinuation 
Oral steroids above 10mg/day was 
updated to 20mg/day. 
Updated to provide consistency 
with other changes in the protocol.  
6.5 Dose modification 
Individual requirements for 
splenectomized patients were 
removed. 
Updated for consistency with the 
changes in Section 10.22. 
6.5 Dose modification 
A sentence was added to state that 
Dose modifications or temporary 
IMP treatment discontinuation are 
permitted if serum IgG value 
are<1g/L (Section 10.22). 
Updated for consistency with the 
changes in Section 10.22. 
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Section # and Name 
Description of Change 
Brief Rationale 
6.6 Self-administration  
A new subsection was added 
regarding details for self-
administration 
Updated and introduced as a 
separate section to provide more 
details on the optional IMP self-
administration 
6.7 Home visits   
A new subsection was added 
regarding details for home visits 
Updated to separate the optional 
self-administration from the home 
visits and to provide more details 
on the optional home visits 
7.1.1 Liver chemistry 
stopping criteria  
Figure 7-1 
Figure 7-2 
Cross reference to Appendix 6 was 
corrected to Appendix 5. 
Updated to provide the correct 
reference   
7.1.2 QTc stopping criteria  Triplicate ECG was removed 
Updated to reflect the changes in 
Section 8.1.3. 
7.1.3 Discontinuation of 
IMP due to other adverse 
events or medical 
condition 
The text was updated to clarify that 
the list is not intended to be all 
inclusive and the investigator is 
expected to apply his/her judgment 
on continuing IMP based on the 
clinical situation at hand. 
Updated to provide clarity  
7.1.4 Temporary IMP 
discontinuation 
Text was updated to clarify that: 
A study participant may 
temporarily discontinue IMP if any 
of the following events occur:  
3. A severe AE of headache that 
is considered related to the 
IMP in the opinion of the 
investigator (Section 10.20).  
4. A splenectomised study 
participant develops a 
(persistent or re-occurring) 
nonserious infection, as per 
investigator’s decision 
(Section 10.22). 
5. Total serum IgG values goes 
<1g/L as per investigator’s 
decision (Section 10.22). As 
IMP treatment is 
administered 
 the 
decision is based on the most 
recently available total IgG 
value. In order to maintain 
 
 
 
 
To be consistent with Section 
20.20. 
 
 
 
To reflect changes in the process of 
managing infections and events of 
hypogammaglobulinemia and for 
consistency with the changes in 
Section 10.22. 
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Section # and Name 
Description of Change 
Brief Rationale 
the blind from the parent 
studies, IgG, IgG subclasses, 
total protein, and albumin 
values will be unblinded 
starting with the blood 
samples taken at Week 4 
(Visit 5).  
7.2 Participant 
discontinuation/withdrawal 
from the study 
#3 was added as follows: 3. An 
adverse event or a medical 
condition as described in Section 
7.1.1, Section 7.1.2 or Section 7.1.3 
occur. 
Added for consistency throughout 
the protocol.  
7.3 Lost to follow-up 
“to complete the final evaluation” 
was deleted from the last 
bulletpoint 
No final evaluation is required for 
a study participant who is lost to 
follow-up. 
8.1.2 Vital signs  
Body temperature was added to the 
list of vital signs to be measured 
before blood samples are taken. 
Updated for further clarity and 
consistency throughout the 
protocol. 
8.1.3 Electrocardiograms 
Text was updated to remove 
references to triplicate 
ECGs:“Triplicate 12 lead ECG” 
ECG was replaced with “A 12-lead 
ECG.” 
No identification of cardio-toxicity 
from non-clinical data, supported 
by lack of signal of cardiac events 
in the rozanolixizumab-
program.  Updated in order to 
decrease the burden to the sites and 
study participants.  
8.1.5 Assessment and 
management of TB and TB 
risk factors 
The text was updated to remove 
“appropriate rigorous” and to add 
that assessment and management of 
TB and TB risk factors should 
follow local or national guidelines.  
Patients 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 already excluded from 
TP0003/TP0006, therefore the 
sites are expected to follow 
national/local guidelines for the 
management of TB, in case 
needed. 
In addition, the mechanism of 
action of rozanolixizumab is 
expected to have little or no impact 
on the immune response against 
intracellular organisms which is 
involved in controlling the 
infection with Mycobacterium 
tuberculosis.  
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Section # and Name 
Description of Change 
Brief Rationale 
8.1.5.1 Tuberculosis 
assessment  
Sections on physical examination 
for TB, TB assessment by IGRA, 
and TB assessment by chest x-ray 
were removed.  
Updated for consistency with 
Section 8.1.5 
8.1.5.2 Tuberculosis 
management 
Test conversion for IGRA was 
removed. Under Latent TB, text 
regarding 2 indeterminate IGRA 
test results as suggestive of TB 
infection was removed. 
Updated for consistency with 
Section 8.1.5 
8.1.5.2 Tuberculosis 
management 
The definition for LTBI was 
updated.  
The definitions for active TB and 
NTMBI were added.  
LTBI definition updated as per 
WHO and CDC guidelines. Active 
TB and NTMBI definitions as per 
WHO and CDC guidelines were 
added for consistency.  
8.1.5.2 Tuberculosis 
management 
Text pertaining to AE reporting for 
Latent TB was removed.  
Updated for consistency in 
reporting any TB related AEs as 
per Section 8.1.5.1. 
8.2.8 Adverse events of 
special monitoring 
Text was added to state that the 
headache questionnaire should also 
be completed in case of moderate 
headache although moderate 
headache is not considered an 
AESM. 
Updated for consistency with the 
changes in Section 10.20. 
8.4 Treatment of overdose  
The numbered list was changed to 
bullet points.  
Formatting correction.  
8.5.1 Platelet counts 
Reference to the maintenance 
treatment arm was removed. 
The endpoints related to the 
Exploratory Treatment Arm were 
removed. 
Platelet count endpoints were 
updated. 
Updated to provide consistency 
within the protocol 
8.7 Pharmacodynamics 
A sentence was added to state that 
results of the ITP-specific 
autoantibodies analyses will not be 
outlined in the Clinical Study 
Report for this study. 
Analysis of the ITP-specific 
autoantibodies is a lengthy method 
and therefore the results will be 
provided in a separate report. 
8.8 Exploratory 
biomarkers  
α- and β-globulinswere removed.  
Sampling of α- and β-globulins 
was removed to decrease study 
complexity, as scientific value of 
the evaluation is limited. 
8.8 Exploratory 
biomarkers 
The text was updated to add 
“and/or serious.” 
Updated to provide consistency 
within the protocol. 
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Section # and Name 
Description of Change 
Brief Rationale 
8.9 Immunology 
biomarkers  
The serum complements sample 
4 hours postdose at Baseline and 
Visit 23 (Week 33) was removed.  
Updated to provide consistency 
within the protocol. 
8.9 Immunology 
biomarkers 
Serum cytokines were deleted. 
Blood sampling for cytokine 
analysis was removed in the ITP 
protocols as samples have been 
collected in other rozanolixizumab 
studies and no additional 
information is expected from the 
ITP population. 
9.1 Definition of analysis 
sets  
The Exploratory Treatment Arm 
Safety Set was removed.  
Updated to provide consistency 
within the protocol. 
9.3 Estimands  
Safety Set and estimand was 
updated to state “who started 
TP0004 on 
 dosing.” 
Updated to reflect that estimand 
concerns subjects who started on 
 dosing. 
9.3 Estimands 
A further secondary safety 
estimand, also based on “treatment 
policy” was added.  
Updated to reflect the two dosing 
regimens. 
9.4 Planned safety analysis 
The text was updated to add 
“started TP0004 on 
 or 
 dosing” 
Updated to reflect change in 
dosing regimen. 
9.5 Planned 
efficacy/outcome analyses  
The text was updated to add 
“started TP0004 on 
 or 
 dosing” 
Updated to reflect change in 
dosing regimen. 
9.5 Planned 
efficacy/outcome analyses 
The wording for the secondary 
efficacy endpoints were updated.   
Updated to reflect change in 
dosing regimen and the removal of 
exploratory arm. 
9.6.1 Analysis of 
pharmacodynamic 
endpoints 
α- and β-globulins were removed.  
Updated for consistency with 
Section 8.8. Sampling of α- and β-
globulin biomarkers were removed 
to decrease study complexity, as 
scientific value of the evaluation is 
limited. 
9.6.1 Analysis of 
pharmacodynamic 
endpoints 
9.6.2 Analysis of 
pharmacokinetics 
endpoints  
Text was updated to state “by 
dosing regimen” 
Updated to reflect the change in 
dosing regimen. Analysis can be 
done based on 
 or 
 
dosings. 
9.10 Determination of 
sample size 
The text was updated to state “up to 
a maximum of” 
Updated to provide further clarity  
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Section # and Name 
Description of Change 
Brief Rationale 
10.2 Appendix 2: Clinical 
laboratory tests 
Table 10-1 Protocol-
required safety laboratory 
assessments 
Assessment of % platelet 
reticulocytes and associated 
footnotes were removed.  
Updated to reflect that the analysis 
will not be performed.  
10.2 Appendix 2: Clinical 
laboratory tests 
Table 10-1 Protocol-
required safety laboratory 
assessments 
Low-density lipoprotein (LDL), 
High-density lipoprotein (HDL), 
Total cholesterol and Triglycerides 
were moved under Clinical 
Chemistry. 
Moved under clinical chemistry as 
these will be measured as part of 
clinical chemistry panel.  
10.2 Appendix 2: Clinical 
laboratory tests 
Table 10-1 Protocol-
required safety laboratory 
assessments 
Footnote e was updated as follows: 
“Includes total IgG, IgG subclasses, 
IgA, IgM, and IgE. Results of the 
IgG testing will be unblinded 
starting with the blood samples 
taken at Week 4 (Visit 5 ) in 
TP0004 in order maintain blind of 
from the parent studies. 
To be consistent with Section 22.  
10.5 Appendix 5: Liver 
safety 
Table 10-4 Phase 3-4 liver 
chemistry increased 
monitoring criteria with 
continued IMP 
The cross reference to the liver 
chemistry stopping criteria was 
corrected.  
Updated to provide the correct 
reference. 
10.7, Appendix 7: 
Country-specific 
requirements 
France 
The visit window of +7 days was 
updated to +3 days.  
Updated to align with the updated 
visit window.  
10.7, Appendix 7: 
Country-specific 
requirements 
Japan 
TB assessment and chest x-ray for 
TB were removed.  
Updated for consistency 
throughout the protocol. 
10.7, Appendix 7: 
Country-specific 
requirements 
Japan 
A cross reference was added to 
Table 10-2 and the wording was 
updated.  
Updated for clarity.  
10.7, Appendix 7: 
Country-specific 
requirements 
Section 10.7.1 was added to list the 
countries where self-administration 
will be offered as an option  
Updated to provide further clarity 
on the countries where self-
administration will be offered as an 
option 
10.9 Appendix 9: 
Abbreviations and 
trademarks 
Additional abbreviations and 
definitions were added for: 
General update.  
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Section # and Name 
Description of Change 
Brief Rationale 
CDC, eqv, HCP, QW, RO, and 
WHO. 
10.20 Appendix 20: 
Management of headache 
The text was updated to clarify the 
management of IMP administration 
including dose adjustment 
following an AE of headache. 
Updated to reflect the current 
general program guidance for the 
management of headaches. 
10.22 Appendix 22: 
Management of infections 
and 
hypogammaglobulinemia 
The text was updated to clarify the 
management of IMP administration 
including dose adjustment 
following episodes of infections 
and hypogammaglobulinemia. 
The total serum IgG cut-off value 
for informing the investigators has 
been aligned for all study 
participants based on the lack of 
conclusive literature supporting the 
previous approach.  
The investigators are given total 
flexibility in deciding if and how 
to continue the IMP treatment in 
cases of total IgG values < 1g/L, 
based on a holistic approach of the 
study participant’s status (platelets 
response, signs & symptoms of 
nonserious/ serious infection, 
potential risk of acquiring a 
nonserious/ serious infection).  
10.23 Appendix 23: 
Management of infusion 
reactions or 
hypersensitivity reactions 
Serum cytokines were removed. 
Blood cytokine sampling was 
removed as analysis of cytokines is 
not required in the ITP protocols as 
samples have been collected in 
other rozanolixizumab studies and 
no additional information is 
expected from the ITP population. 
10.25. Appendix 25: 
Protocol Amendment 
History  
Protocol amendment 2 (global 
amendment) has been added. 
Appendix no. 26 was corrected to 
no. 25 
General update. 
Throughout 
Minor editorial and formatting 
changes have been made. 
Minor, therefore have not been 
summarized. 
 
 
Amendment 1 (11 May 2021) 
Overall Rationale for the Amendment 
The primary reason for this protocol amendment was to incorporate changes in the objectives, 
endpoints, the statistical analysis section, as well as a specific study objective and endpoint on 
post-vaccination biomarkers in study participants who have received a COVID-19 vaccine. Other 
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Clinical Study Protocol Amendment 4 
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Page 178 of 199 
changes include incorporating local protocol amendments (0.1- Japan and 0.2-France only) into 
one global protocol. 
Additional updates were incorporated to provide further clarity on the protocol or to correct 
errors. 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Section # and Name 
Description of Change 
Brief Rationale 
Global 
Minor administrative, consistency, 
formatting and typographical 
changes have been made. 
The duration for the treatment 
period was clarified from 52 weeks 
to 54 weeks. 
Updated to provide clarity and be 
consistent with remainder of 
protocol. 
Updated to provide clarity, where 
the 54-week treatment period 
includes a 2-week observation 
period after Week 52. 
Global 
Japan-specific requirements have 
been highlighted throughout the 
protocol and added to Appendix 7, 
Section 10.7. 
In accordance with local 
requirements and actual condition 
of medical treatment in Japan. 
Serious adverse event 
reporting  
For serious adverse event reporting 
(24h), the fax number for Japan has 
been removed.  
For participants in Japan only: 
Additional reporting instructions 
for SAE reporting (investigational 
device) and device deficiency 
reporting specific for Japan have 
been included. 
In accordance with local 
requirements in Japan. Reporting 
instructions are included in the 
event the site uses devices that are 
not approved. a 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
For several objectives, wording on 
maintenance or exploratory dosing 
has been included. 
Updated to provide clarity on 
which study population the 
objective applies to. 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
The primary objective has been 
changed to remove the following 
word, "repeated.” 
The following text has been added 
to the safety endpoint: 
Occurrence of TEAEs leading to 
permanent withdrawal of 
investigational medicinal product 
(IMP) (ie, study discontinuation) 
The other safety endpoint specific 
to occurrence of AESM was 
updated to read as “treatment-
emergent AESM”  
Updated to provide further clarity. 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
Confidential 
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Section # and Name 
Description of Change 
Brief Rationale 
The following word, "repeated" has 
been removed from the secondary 
and exploratory objectives relating 
to assessment the long-term clinical 
efficacy. 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
For several endpoints, "first 
Complete Response" has been 
removed and "during both 
maintenance dosing and 
exploratory dosing" has been 
added. 
Updated to provide clarity with the 
data collected for the study. 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
The secondary efficacy endpoint 
was amended to include "over the 
planned 54-week Treatment 
Period" 
Updated to allow flexibility for 
potential calculation based on 
available visits for participants 
prematurely withdrawn from the 
study. 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
Footnotes have been updated: 
Footnote b, now a: Treatment cycle 
is defined as the period between 
two consecutive doses, unless 
otherwise noted in the Statistical 
Analysis Plan.  
Footnote b: Baseline definitions for 
the maintenance and exploratory 
arm treatment cycles will be 
detailed in the SAP. 
Updated to provide definitions for 
Treatment cycle and Baseline for 
the Maintenance and Exploratory 
Treatment arms (maintenance and 
exploratory dosing). 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
The other efficacy endpoints have 
been updated to include several 
changes, and two new endpoints, as 
listed below:  
- Stable Response defined as 
platelet count ≥30x109/L and 
absence of bleeding without rescue 
therapy at ≥70% of the visits over 
the planned 54-week Treatment 
Period starting after the second 
dose of rozanolixizumab (Week 4) 
- Cumulative number of weeks 
with platelet counts ≥30x109/L over 
the planned 54-week Treatment 
Period  
- Mean Change from Baseline  in 
platelet count at each visit 
- The rescue medication endpoint 
was changed from Time to first 
Updated as per query from the 
FDA on endpoints related to 
efficacy. 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
Confidential 
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Section # and Name 
Description of Change 
Brief Rationale 
rescue medication to "Use of 
rescue medication by visit"  
Additionally, the following 
endpoints were removed:  
- Complete Response, defined as 
platelet count ≥100x109/L, 
confirmed on at least 2 consecutive 
occasions, and absence of bleeding 
- Usage of rescue therapy 
1.1 Synopsis – Objectives 
and Endpoints 
3 Objectives and endpoints 
The following endpoint related to 
ITP bleeding score has been 
changed to "ITP-BAT bleeding 
events and severity by visit" 
Updated to specify the bleeding 
assessment tool to be used and 
clarification of the timepoint. 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
A new secondary objective has 
been added:  
To assess the effect of 
rozanolixizumab on study 
participant perceived symptoms 
Updated to reflect that only the 
ITP-PAQ Symptoms domain score 
will be assessed for the secondary 
HRQoL objective. 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
The exploratory endpoints related 
to the effect of rozanolixizumab on 
health-related quality of life 
(HRQoL) have been modified. 
The secondary objective related to 
HRQoL has moved to be an 
exploratory objective. 
The following endpoint, Response 
defined as change from Baseline at 
or above the defined threshold for 
ITP-PAQ Symptoms domain score 
has been deleted.  "Change from 
baseline endpoint" was moved to 
the exploratory PRO objective. 
Updated to provide clarity and to 
include missing details from 
previous version of the protocol. 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
The secondary endpoints for 
change from Baseline in serum IgG 
subclasses and concentrations have 
been moved to exploratory 
endpoints. 
Minimum absolute IgG value and 
maximum decrease from Baseline 
in total serum IgG concentration 
over time are kept as secondary 
endpoints. Change from baseline in 
total IgG, IgG- subclasses and IgA, 
IgE and IgM over time are as other 
endpoints. 
1.1 Synopsis – Objectives 
and endpoints 
3 Objectives and endpoints 
The secondary objective related to 
reduction in use of steroid has been 
updated to include also other 
concurrent ITP medications, and 
the associated endpoint has been 
Updated to reflect that the analysis 
of changes in concomitant ITP 
therapies will not be limited only 
to corticosteroids. 
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04 Apr 2022 
Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
Page 181 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
modified to replace "reduction" 
with "change”" 
1.1 Synopsis – Objectives 
and Endpoints 
3 Objectives and endpoints 
1.3 Schedule of Activities, 
Tables 1-1 and 1-2 
The PRO name for Physical 
Fatigue Instrument has been 
changed to the "FATIGUE-PRO 
Physical Fatigue scale.” 
Updated to indicate the correct 
name of the PRO. 
1.1 Synopsis – Objectives 
and Endpoints 
3 Objectives and 
Endpoints 
Secondary and exploratory: 
Additional wording has been 
provided for clarification that the 
minimum value from Baseline in 
total serum IgG concentration 
refers to the absolute IgG value. 
Updated wording to clarify that 
total serum IgG will be measured in 
addition to the IgG subclasses.  
Updated to provide further clarity. a 
 
 
 
 
 
 
1.1 Synopsis – Objectives 
and Endpoints 
3 Objectives and endpoints 
Two new exploratory endpoints 
related to clinical efficacy in study 
participants with first exposure to 
rozanolixizumab have been added.   
Added to specifically analyze 
efficacy in participants that 
switched from placebo to 
rozanolixizumab treatment in the 
OLE study. 
1.1 Synopsis – Objectives 
and Endpoints 
3 Objectives and endpoints 
Exploratory endpoints: In relation 
to Complete Response by visit 
within 1 treatment cycle without 
rescue, the endpoint has been 
amended to "Platelet count 
≥30x109/L by visit within 1 
treatment cycle without rescue 
therapy per treatment cycle"  
Updated for consistency to delete 
Complete Response endpoints and 
to focus on platelet counts 
≥30x109/L and Clinically 
Meaningful Response. 
1.1 Synopsis – Objectives 
and Endpoints 
3 Objectives and endpoints 
A new objective and the associated 
endpoints related to study 
participants experience with 
subcutaneous self-administration 
have been included.  
For participants that are eligible to 
use self-administration this 
questionnaire was added to capture 
their experience. 
1.1 Synopsis – Objectives 
and Endpoints 
Exploratory: 
Changed pneumococci to 
Streptococcus pneumoniae and 
meningococci to Neisseria 
meningitidis 
Corrected spelling of Haemophilus 
influenzae  
Updated for consistency with the 
table in Section 3. a 
 
 
 
Error in original protocol. a 
1.1 Synopsis – Objectives 
and Endpoints 
3 Objectives and endpoints  
The following exploratory endpoint 
has been removed: "Percent change 
from Baseline in vaccination titers 
Vaccination titers against tetanus 
will not be measured in this study. 
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04 Apr 2022 
Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
Page 182 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
against tetanus in all study 
participants" 
1.1 Synopsis – Objectives 
and Endpoints 
3 Objectives and endpoints 
The objective on assessing clinical 
efficacy in the Exploratory 
Treatment Arm has been amended 
to remove "long-term" and include 
"intermittent.”  
The associated endpoint has been 
updated to remove “average” 
Updated to be consistent with 
study design. 
 
 
 
Updated to ensure clarity with the 
associated objective.   
1.1 Synopsis  
3 Objectives and 
Endpoints 
An additional objective and 
associated endpoint specific to the 
effect of rozanolixizumab on 
COVID-19 biomarkers the has 
been included. 
New objective and endpoint is 
needed for the collection of 
information on post-vaccination 
biomarkers for participants who 
have received the COVID-19 
vaccination.  
1.1 Synopsis, Overall 
Design 
4.1 Overall design 
Additional wording on which 
treatment will the study participants 
receive upon entering the 
Maintenance Treatment arm has 
been included. 
Updated to provide further clarity. 
1.1 Synopsis, Overall 
Design 
4.1.2 Exploratory 
treatment arm 
The following wording "a 
proportion of" and “most recently” 
have been added in reference to 
participants paused from treatment 
in the Maintenance Treatment Arm 
and randomized to the Exploratory 
Treatment Arm. 
Updated to provide further clarity. 
1.1 Synopsis – Overall 
Design 
 
Details have been added to explain 
that a
 total dose 
corresponds to an average 
 
dose in a participant weighing 
70kg. 
Updated to provide further clarity. 
1.1 Synopsis – Overall 
Design 
4.1.2 Exploratory 
treatment arm 
Additional wording added ("ie, no 
need for rescue therapy") to clarify 
criteria for study participant to 
return to Maintenance Treatment 
Arm. 
Updated to provide further clarity. a 
1.1 Synopsis, Overall 
Design 
4.1.1 Maintenance 
treatment arm 
4.1.2 Exploratory 
treatment arm 
6.4.3 Rescue therapy 
The following wording "dose 
and/or type" has been added in 
reference to study participants 
possibly being withdrawn if they 
receive rescue therapy. 
Updated to provide further clarity. 
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Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
Page 183 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis, Overall 
Design 
In relation to tolerability issues, the 
following term "side effects" has 
been amended to replace "side" 
with "adverse.”  
Updated to provide clarity and be 
consistent with remainder of the 
protocol. 
1.1 Synopsis, Overall 
Design 
4.1 Overall design 
9.9.2 Data monitoring 
The following sentence has been 
removed: "the IDMC will be the 
same as used for the parent studies 
TP0003 and TP0006, but data from 
each study will be presented 
separately" 
Updated to be consistent with the 
IDMC Charter. 
1.1 Synopsis, Number of 
Participants 
9.10 Determination of 
sample size 
The maximum number of 
participants completing TP0003 or 
TP0006 planned for enrollment into 
TP0004 has reduced from 210 to 
180. 
Number of participants has been 
changed based on revised sample 
size calculation method and 
assumptions in the parent studies, 
TP0003 and TP0006 leading to 
reduction of participants in 
TP0004. 
1.1 Synopsis, Treatment 
Groups and Duration  
4.1 Overall Design 
 
The following wording has been 
added "includes a 2-week 
observation period after Week 52" 
Updated to provide further clarity 
on the total duration of the 
maintenance treatment period. 
1.3 Schedule of Activities, 
Table 1-1 (Maintenance 
treatment arm) 
For participants in Japan only: 
IGRA TB test has been added to 
EOS/EW Visit.  
To confirm safety at study 
termination. a 
1.3 Schedule of Activities, 
Table 1-1 (Maintenance 
treatment arm) 
New assessments specific to 
COVID-19 vaccination samples 
and the associated footnotes have 
been added. 
New details on platelet count 
assessments have been added as a 
new footnote (f).  
Subsequent footnotes have been 
reordered. 
Included as part of the objective on 
post-vaccination biomarkers for 
participants who have received the 
COVID-19 vaccination. 
1.3 Schedule of Activities, 
Table 1-1 (Maintenance 
treatment arm) 
Tetanus titer has been removed.  
Vaccination titers against tetanus 
will not be measured in this study. 
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04 Apr 2022 
Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
Page 184 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of Activities, 
Table 1-1 (Maintenance 
treatment arm)  
Additional activities have been 
added: Pre-SIAQ and Post-SIAQ 
(Infusion version).  
The following footnotes have been 
added:  
y For study participants who self-
infuse, to be completed once, prior 
to first self-infusion 
z To be completed within 1 hour 
after the first self-infusion and the 
next consecutive self-infusion 
Added participant self-
administration questionnaire to 
capture their experience. 
 
1.3 Schedule of Activities, 
Table 1-1 (Maintenance 
treatment arm) 
Footnote d: Reworded to state that 
the data will be transferred from the 
Week 25 (Visit 28) from TP0003 or 
TP0006.  
Footnote f now g: Updated to 
clarify participants will need a new 
platelet count. 
Footnote g, now h: The following 
wording has been removed: "1 to 2 
minutes" 
Footnote i, now j: Updated to 
include "and prior to discharge 
from clinic/departure of home 
healthcare professional" 
Footnote j, now k: Additional 
laboratory samples (total 
cholesterol, LDL, HDL, and 
triglycerides) will be collected at 
Week 13 and Week 25 only. 
For participants in Japan only: 
Footnote o: Wording pertaining to 
T-SPOT.TB test may be performed 
as an alternative. 
Footnote t, now aa: updated to 
include cross-reference to the 
management of headaches 
Updated to correct timepoint when 
data will be taken from the parent 
studies. a  
 
Updated to provide further clarity.  
 
 
Updated to provide further clarity. 
 
 
Updated to provide further clarity. 
 
 
 
Lipid profile will be assessed 
during the study. 
 
 
 
To add the T-SPOT test as a 
recommended IGRA test in 
addition to the QuantiFERON test. 
a 
Updated to provide further clarity. 
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Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
Page 185 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of Activities, 
Table 1-1 (Maintenance 
treatment arm) 
Footnote n, now q: Corrected 
footnote to state that observation 
time of 1 hour is required for the 
next 2 IMP infusions after Visits 1 
and 5, and additional wording was 
added to specify that the infusions 
need to be well tolerated by the 
study participant to reduce 
observation time to 15 minutes for 
the remaining visits until Week 25. 
Additional wording specific to the 
criteria for no post-infusion 
observation periods after Week 25 
has been included.    
Updated to remain consistent with 
the observation requirements and 
the overall study design 
(Section 4.1). 
1.3 Schedule of Activities, 
Table 1-2 (Exploratory 
treatment arm) 
Table header was updated to 
include the correct visit numbers to 
correlate with the weeks. 
Correction of error in footnote b to 
correlate with updates to header 
correction. 
Error in original protocol. a 
1.3 Schedule of Activities, 
Table 1-2 (Exploratory 
treatment arm) 
Added a scheduled visit for platelet 
count (local laboratory) at Week 
35. 
For laboratory parameters, "local" 
was replaced with "central.”  
Error in original protocol. a 
1.3 Schedule of Activities, 
Table 1-2 (Exploratory 
treatment arm) 
Collection of anti-rozanolixizumab 
antibodies (ADA) samples was 
removed at Weeks 29, 37 and 41. 
Additional ADA samples will 
already be collected at scheduled 
visits for plasma concentration of 
rozanolixizumab samples. 
1.3 Schedule of Activities, 
Table 1-2 (Exploratory 
treatment arm) 
Correction of typographical error in 
footnote b, ≥50x109/L and added 
"to ≤200x109/L.” 
Footnote e: Replaced "final" with 
"each" dose of IMP. 
Footnote f now g: The following 
wording has been removed: "1 to 2 
minutes" 
Footnote f: A new footnote specific 
to withdrawal criteria has been 
added.  
Footnote g now h: The following 
wording was added: "and prior to 
discharge from clinic/departure of 
home healthcare professional.” 
Updated for consistency with 
Overall Design in Section 1.1. a 
 
Updated to correct an error. a 
 
Updated to provide further clarity. 
 
 
Updated for consistency with the 
protocol. 
 
Updated to remain consistent with 
the post-infusion observation 
requirements and the overall study 
design (Section 4.1). 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
Confidential 
Page 186 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
Footnote j: A new footnote specific 
to instructions if study participant 
requires IMP dosing. 
Footnote k and m: New footnotes 
specific to platelet count at the time 
of the visit. 
Footnote l: Durations of the post-
dosing observation period have 
been updated. 
 
 
 
Updated to be consistent across the 
Phase 3 rozanolixizumab clinical 
program for an OLE study. 
1.3 Schedule of Activities, 
Table 1-2 (Exploratory 
treatment arm) 
Footnotes l and k, now o and p, 
respectively: postdose has been 
replaced with postevent. 
Updated to correct an error. 
1.3 Schedule of Activities, 
Table 1-2 (Exploratory 
treatment arm) 
Added the following footnote (l) to 
the administration of IMP: 
"Study participants are to stay at 
the study site for 4 hours after the 
first IMP infusion. The observation 
will be 2 hours after the second 
dose, and 1 hour for the remaining 
dosing visits" 
Reordering of footnotes was 
required. 
To provide details of post-infusion 
observation time for consistency 
with Section 4.1. a 
1.3 Schedule of Activities, 
Table 1-2 (Exploratory 
treatment arm) 
Additional activities have been 
added: Pre-SIAQ and Post-SIAQ 
(Infusion version).  
The following footnotes have been 
added:  
q For study participants who self-
infuse, to be completed once, prior 
to first self-infusion 
r To be completed within 1 hour 
after the first and second 
consecutive self-infusion  
Added participant self-
administration questionnaire to 
capture their experience. 
 
2.2 Background 
Additional studies have been 
included to this section.  
"Ongoing" has been removed from 
Study UP0060. 
Updated to be consistent. 
 
The study is complete. 
2.3 Benefit/risk assessment Text on potential risks associated 
with administration of 
rozanolixizumab has been updated. 
New wording on COVID-19 
vaccines has been added. 
Updated to be consistent across the 
Phase 3 rozanolixizumab clinical 
program. 
4.1 Overall Design 
Wording referring to the medical 
monitor decision on whether 
This deletion has been made due to 
the medical monitor’s role in 
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Clinical Study Protocol Amendment 4 
Rozanolixizumab 
TP0004 
 
 
 
Confidential 
Page 187 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
participants can be enrolled has 
been removed. 
determining a study participant’s 
eligibility in TP0004 not being 
considered valid. 
4.1 Overall Design 
 
Several minor edits were made for 
consistency with other sections in 
the protocol. 
Wording referring to the medical 
monitor’s decision on whether 
participants can be enrolled and 
participants receiving a vaccination 
titer for tetanus have been removed. 
Wording pertaining to the next step 
for to study participants previously 
randomized to placebo has been 
added.  
Post-infusion observation timings 
and instructions for the 
maintenance and exploratory 
treatment arms have been updated. 
 
 
 
Update due to the medical 
monitor’s role in determining a 
study participant’s eligibility not 
considered valid. 
 
Updated for consistency with 
footnote m in Table 1-1. a  
 
 
Updated to be consistent across the 
Phase 3 rozanolixizumab clinical 
program for an OLE study. 
 
4.1 Overall Design 
A new sentence has been added to 
explain that contingency measures 
during a pandemic and other 
exceptional circumstances have 
been included. 
Contingency measures have been 
implemented to ensure study 
participant safety in response to the 
COVID-19 pandemic causing the 
inability for sites to adhere to 
protocol visits and assessments. 
4.1 Overall Design,  
Table 4-1, footer 
4.1.1 Maintenance 
treatment arm 
 
Table header updated to replace 
"starting" with "Exploratory arm.”  
Additional wording has been 
provided for clarification on the 
action taken for study participants 
with on the lowest dose level with a 
platelet count between >200×109/L 
and <400 ×109/L. 
This update has been included to 
consider that no dose reduction to 
less than 
(fixed dose) is set. 
a   
4.1.2 Exploratory 
treatment arm 
This section has been updated to 
include: 
"or the investigator deems not to be 
suitable" in reference to entry to the 
Exploratory Arm, and additional 
information on based on rescue 
therapy.   
Week 23 and Visit 18 have been 
included. 
Updated to provide further clarity. 
4.3 Justification for dose 
The following wording, "then 
quickly reset platelets to the 
desired levels as faster onset of 
Updated to provide further clarity. 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
Confidential 
Page 188 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
response" has been replaced with 
"is anticipated to increase platelet 
count to ≥50x10 within a week as.” 
In addition the following sentence 
has been included: "However, if 
any safety concerns are identified 
in the parent studies, TP0003 and 
TP0006, corresponding changes 
will be made in the TP0004 dosing 
scheme" 
5.1 Inclusion criteria 
Criterion #1, now 1a,  has been 
modified to remove "and sponsor" 
from the criterion. 
This deletion has been made as the 
sponsor cannot be involved in 
deciding a study participant’s 
eligibility in TP0004. 
5.2 Exclusion criteria 
Criterion #2 has been removed.  
This deletion has been made due to 
the medical monitor’s role in 
determining a study participant’s 
eligibility in TP0004 not being 
considered valid. 
5.2 Exclusion criteria 
Criterion #6, now 6a: The 
following text has been removed:  
"In case of a clinically relevant 
increase, inclusion of the study 
participant must be discussed with 
the Medical Monitor or designee." 
Criterion #7, now 7a: the criterion 
has been updated to include a 
timepoint.  
This deletion has been made due to 
the medical monitor’s role in 
determining a study participant’s 
eligibility in TP0004 not being 
considered valid. 
 
Updated to provide clarity on 
bilirubin values used at the time of 
eligibility. 
5.2 Exclusion criteria 
Criterion #9, now 9a: the criterion 
has been updated to include 
"major" in reference to planned 
surgery and the duration of 14 
months has been replaced by study 
period. 
Criterion #10, now 10a: the 
criterion has been updated to 
include "at the last available 
assessment in TP0003/TP0006" 
Updated to remain consistent with 
the parent studies. 
 
 
 
 
Updated to provide clarity on lab 
values used at the time of 
eligibility. 
5.2 Exclusion criteria 
Criterion #11, now 11a: The 
following text has been removed:  
"and any queries regarding 
continuation of the study 
participants will have to be 
addressed with the medical 
monitor." 
 
 
This deletion has been made due to  
the medical monitor’s role in 
determining a study participant’s 
eligibility in TP0004. 
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04 Apr 2022 
Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
Confidential 
Page 189 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
"The ECG contains findings that 
may represent a significant 
abnormality" 
 
This is not applicable and remains 
consistent with the parent studies. 
5.2 Exclusion criteria 
New criteria on renal impairment 
and QT interval (#12 and #13), and  
live vaccination prior to, during or 
after the study (#14) have been 
included. 
Updated to be consistent across the 
Phase 3 rozanolixizumab clinical 
program for an OLE study. 
5.2 Exclusion criteria 
New wording on France-specific 
requirements has been included. 
Updated to align with French 
Ethics Committee query on 
exclusion criteria pertaining the 
French Public Health Code and 
participant’s age at Baseline. b 
6 Study treatments, Table 
6-1 
The description for unit doses, and 
packaging and labelling for the 
maintenance and exploratory arms 
has been updated to delete: "6mL" 
and "no less than 4.0mL extractable 
volume of.” 
Update to reflect the foreseeable 
changes in vial size. 
6.2 Measures to minimize 
bias: randomization and 
blinding 
The following text has been added 
to: The randomization number will 
be incorporated from the IRT into 
the eCRF by automatic data 
transfer. 
Updated to provide further clarity. 
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies) 
Added "above Baseline (Visit 1, 
TP0004)" to the following 
sentence: 
Any increase in concomitant ITP 
medication above Baseline (Visit 1, 
TP0004) is regarded as rescue 
therapy. 
New text has been added in specific 
to the requirement to collect 
information on COVID-19 
vaccinations in the eCRF. 
Updated to provide further clarity. a 
 
 
 
 
 
 
Information on COVID-19 
vaccination will be required. 
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies), Table 6-2 
"Prednisolone" changed to 
"prednisone.” Clarification of dose 
for oral corticosteroid.  
Dosing for cyclosporin was 
updated to include modified and 
unmodified doses.  
Addition of Eltrombopag, 
Avatrombopag and Fostamatinib at 
any dose as permitted concomitant 
treatments.  
Updated to clarify permitted 
concomitant medications. a 
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Clinical Study Protocol Amendment 4 
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TP0004 
 
 
 
Confidential 
Page 190 of 199 
Section # and Name 
Description of Change 
Brief Rationale 
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies) 
The following wording has been 
removed: "When applicable, the 
study participant must be on a 
stable dose of cannabidiols and/or 
medicinal marijuana for Visit 1 
(Day 1)" 
No fixed period of stable dose 
before Baseline for this study. 
6.4.2 Prohibited 
concomitant treatments 
(medications and 
therapies) 
Removal of Dexamethasone, and 
addition of Romiplostim as a 
prohibited treatment, and 
clarification for corticosteroids. 
Updated to clarify prohibited 
concomitant medications. a 
6.4.2 Prohibited 
concomitant treatments 
(medications and 
therapies) 
Removal of TPO-RAs as prohibited 
treatment. 
Updated to clarify prohibited 
concomitant medications. a 
6.4.2 Prohibited 
concomitant treatments 
(medications and 
therapies) 
New wording has been included 
explaining the use of prohibited 
concomitant treatment will lead to 
permanent discontinuation from 
IMP.  
Updated for clarification of 
prohibited medications. 
6.4.3 Rescue therapy  
 
Additional wording to following 
sentence has been included: Any 
increase in concomitant ITP 
medication "above Baseline (Visit 
1, TP0004)" is regarded as rescue 
therapy. 
Additional wording in relation to 
systemically administered 
corticosteroids has been included: 
"ie, pulse, oral and iv steroids" as 
well as "are also considered rescue 
therapy.” 
Updated to clarify rescue therapy. a 
6.4.3.1 Rescue therapy not 
leading to discontinuation 
Platelet count measurement was 
corrected from ≥ to <. 
Additional wording in reference to 
the measures of starting 
rozanolixizumab treatment and 
defining a high dose of 
corticosteroids have been included. 
The increase amount for permitted 
concomitant immunosuppressants 
has been corrected from 5% to 
25%. 
Updated to clarify rescue therapy. a 
6.4.3.2 Rescue therapy 
leading to discontinuation 
TPO-RAs was removed, and 
"initiation" was added in reference 
to additional ITP therapy. 
Updated to clarify rescue therapy. a 
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Section # and Name 
Description of Change 
Brief Rationale 
6.5 Dose modification 
The following recommended dose 
modifications were updated/added: 
- Moderate to severe toxicities 
(Grade 2 and above, as defined by 
Common Terminology Criteria for 
Adverse Events version 5.0) for 
which rozanolixizumab cannot be 
excluded as a cause. 
Wording on potential changes in 
the dosing scheme based on safety 
concerns identified in the parent 
studies has been included. 
Updated to remain consistent 
across the rozanolixizumab 
program. 
6.6 Home visits and 
home/self-dosing 
Sub-heading was changed to 
"Home visits and self-
administration" and additional 
wording has been included 
pertaining to self-administration 
requirements as well as the timing 
of administration.  
The conditions for conducting 
home visits/self-administration 
have been amended.  
Updated to provide clarity and 
remain consistent with study 
design. 
6.7 Treatment after the 
end of the study 
New wording on access to a 
Managed Access Program has been 
included. 
Updated to provide clarity. 
7.1.3 Discontinuation of 
IMP due to other adverse 
events or medical 
condition 
New section was included to detail 
criterion and procedure for any 
discontinuation of IMP due to other 
AEs or medical condition  
Updated to remain consistent with 
Phase 3 ITP clinical program. 
7.1.4 Temporary IMP 
discontinuation 
Section was previously 7.1.3. All 
criteria were amended. 
Additional parameters to be 
unblinded following the second 
dose have been included. 
In addition, details have been added 
for participants that have suspected 
or confirmed COVID-19. 
Updated to provide clarity and 
remain consistent with study 
design and remainder of protocol. 
 
 
Criteria #2 #3, and #5 were 
previously updated in protocol 
amendment 0.1. 
7.1.4 Temporary IMP 
discontinuation 
Clarification that treatment will be 
temporarily discontinued for any 
participant with IgG levels below 
1g/L on any occasion. 
Clarification of formal and 
informal unblinding and the role of 
the unblinded Medical Monitor. 
Updated to clarify when treatment 
discontinuation is required, 
unblinding, and the role of the 
unblinded Medical Monitor. 
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Section # and Name 
Description of Change 
Brief Rationale 
7.2 Participant 
discontinuation/withdrawal 
from the study 
This section was reordered and 
updated to remove repetitive 
information highlighted in Section 
7.1.4. 
Updated to provide clarity and be 
consistent with study design and 
remainder of protocol.  
Correction of error and for 
consistency with parent studies. 
7.3 Lost to follow up 
This section was updated to remove 
repetitive information in relation to 
evaluations and observations. 
To avoid repetition. 
 
8 Study Assessments and 
Procedures 
A new paragraph describing 
contingency measures during a 
pandemic and other exceptional 
circumstances has been included. 
Contingency measures have been 
implemented to ensure study 
participant safety in response to the 
COVID-19 pandemic causing the 
inability for sites to adhere to 
protocol visits and assessments. 
8.1.3 Electrocardiograms 
The following wording has been 
removed: "1 to 2 minutes" 
Updated to provide further clarity. 
8.1.5.1 Tuberculosis 
assessment 
TB signs and symptoms 
questionnaire: "and must receive 
prophylactic LTB infection 
therapy" and "must be withdrawn" 
have been deleted. 
To provide further clarity. 
8.1.5.1 Tuberculosis 
assessment  
If reference to determining if a 
participant has LTBI, wording on 
receiving prophylactic LTBI 
therapy has been removed.  
To provide further clarity on the 
assessment of TB. 
8.1.5.1 Tuberculosis 
assessment  
TB assessment by IGRA:  
Wording on requirements for 
positive or indeterminate IGRA 
tests result has been updated.  
To provide further clarity on the 
assessment of TB.  
8.1.5.2 Tuberculosis 
management 
New text on the recommendation 
for withdrawn participants with 
active TB or NTMB infection to 
enter the SFU Period and attend 
Visit 35 has been included. 
To provide further clarity in line 
with the protocol. 
8.1.6 Splenectomized 
study participants  
The following wording "for the 
whole duration of the study" was 
added in reference to the 
requirement of carrying a 
splenectomy card. 
New wording on the requirement 
for splenectomized study 
participants to have documented 
evidence of vaccinations from 
parent studies has been included.  
Updated to provide further clarity. 
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Section # and Name 
Description of Change 
Brief Rationale 
8.2.5 Pregnancy  
Instructional wording for 
participants with confirmed 
pregnancy has been reordered. 
Updated to provide further clarity. 
8.2.8 Adverse events of 
special monitoring 
A sentence has been added to 
clarify that an AESM is not 
necessarily a serious adverse event 
unless one of the seriousness 
criteria defined in the Appendix 3 
is met. 
Updated to provide further clarity. 
8.2.9 COVID-19 
vaccination  
New subsection has been included 
to ensure AEs considered related to 
COVID-19 are captured.  
Implemented to ensure study 
participant safety in response to the 
COVID-19 pandemic. 
8.5.1 Platelet counts 
Wording on platelet count-related 
endpoints has been updated. 
Updated to be consistent with the 
protocol and reflect the changes 
made for the endpoints. 
8.5.3 Patient Reported 
Outcomes 
The list of PROs has been updated 
to replace the "Physical Fatigue 
Instrument" by the "FATIGUE-
PRO Physical Fatigue scale" and 
"EQ-5D" to "EQ-5D-5L.” 
To indicate the correct name of the 
PRO. 
8.5.3.1 ITP-PAQ 
Additional text on the choice of 
selection as a secondary endpoint 
has been included. 
Updated to be consistent with the 
protocol and reflect the changes 
made for the endpoints 
8.5.3.3 FATIGUE-PRO 
Physical Fatigue Scale 
The "Physical Fatigue Instrument" 
has been replaced by the 
"FATIGUE-PRO Physical Fatigue 
scale.” 
Additional changes were made to 
the description of the FATIGUE-
PRO Physical Fatigue scale. 
To indicate the correct name of the 
PRO. 
8.5.3.7 SIAQ (Infusion 
version) 
An new subsection for an 
additional patient reported outcome 
tool "SIAQ (Infusion version)" has 
been included.  
Added to capture the participants 
experience of  IMP self-
administration. 
8.8 Exploratory 
biomarkers 
Duplicate details pertaining to 
sample collection, processing, 
storage, labeling, and shipping have 
been deleted. 
To remove repetition. 
8.9 Immunological 
biomarkers 
New text has been added in specific 
to blood sampling for the 
measurement of COVID-19 
antibodies. 
COVID-19 antibodies will be 
collected in this study for all 
participants who have received a 
COVID-19 vaccine. 
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Section # and Name 
Description of Change 
Brief Rationale 
9.1 Definition of analysis 
sets 
Definition of analysis sets: The 
Safety Set and Exploratory 
Treatment Arm Set have been 
updated. 
The Pharmacokinetic Per-Protocol 
Set was updated to remove "and no 
important protocol deviations 
affecting the PK variable, as 
confirmed during a pre-analysis 
review of the data prior to database 
lock" 
Updated for further clarity. 
9.2 General statistical 
considerations 
A sentence was added to explain 
that data handling conventions for 
data affected by COVID-19 will be 
detailed fully in the SAP. 
Added to confirm that the potential 
effects of COVID-19 on the data 
analysis will be addressed. 
9.4 Planned safety 
analyses 
This section has been amended to 
remove "8 weeks after the end of 
the Treatment Period" and "in 
study participants who discontinue 
the study or IMP" in reference to 
follow up of exposure to treatment, 
and to include details specific to 
safety analyses.  
Updated for further clarity. 
9.5 Planned 
efficacy/outcome analyses 
Changed "feeder" to "parent" when 
describing TP0003/TP0006 studies. 
New wording has been included to 
provide details and clarification on   
efficacy/outcome analyses. 
Updated for consistency in 
terminology within protocol. a 
Clarification has been provided on 
how assessments will be conducted 
for key efficacy endpoints in study 
TP0004 for patients who received 
rescue medication, especially, near 
the end of the parent studies. a 
9.6.1 Analysis of 
pharmacodynamics 
endpoints 
Total IgG was added to the list of 
included analyses to be considered. 
Updated for to be consistent with 
endpoints listed in the protocol. 
9.6.2 Analysis of 
pharmacokinetics 
endpoints 
The following wording has been 
removed: "stratified by dose 
regimen" and "stratified by 
treatment arm.” 
Updated for further clarity. 
9.7 Handling of protocol 
deviations 
The following wording has been 
removed: "exclusion of participants 
from analysis populations" 
Updated to be consistent with the 
data cleaning plan. 
9.9.1 Interim analysis 
New wording on data cutoffs has 
been included. 
Updated for further clarity. 
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Section # and Name 
Description of Change 
Brief Rationale 
9.9.2 Data monitoring 
Wording on reviewing safety data 
at periodic data reviews has been 
removed. 
Updated to be consistent with the 
IDMC Charter. 
10.1.3 Informed consent 
process 
New wording has been included in 
reference to Japan-specific 
requirements.  
In accordance with local 
requirements in Japan. a  
10.1.5 Committees 
structure 
The following new wording was 
added: "The IDMC will have the 
possibility to unblind the data" 
To be consistent with the rest of 
the protocol. 
 
10.1.6 Data quality 
assurance 
Additional wording on quality 
tolerance limits has been included. 
Correcting an error as this 
information was previously 
omitted from the protocol. 
10.2, Appendix 2: Clinical 
laboratory tests 
Table 10-1: Footnotes have been 
reordered due to addition of 
footnotes b, c, d, e, and g to clarify 
collection timepoints and 
requirements for protocol-required 
safety laboratory assessments. 
Updated for clarification. a 
10.2, Appendix 2: Clinical 
laboratory tests 
Total cholesterol, LDL, HDL and 
triglycerides have been added. 
Table 10-1: Updated wording for 
immunoglobulin footnote g to 
clarify when results are unblinded. 
Glycosylated hemoglobin (HbA1c) 
has been removed.  
Lipid profile will be assessed in 
the study. 
To ensure blinding is consistent 
throughout all studies in the 
rozanolixizumab clinical program.a 
Removed wording to maintain 
consistency within the protocol. 
10.3, Appendix 3: Adverse 
events – definitions and 
procedures for recording, 
evaluating, follow-up, and 
reporting 
Additional wording for follow-up 
of AEs and SAEs has been 
included. 
Updated to ensure guidance for AE 
follow up is consistent with the 
Phase 3 rozanolixizumab clinical 
program. 
10.4, Appendix 4: 
Contraceptive guidance 
and collection of 
pregnancy information, 
Table 10-2 
Wording for vasectomized partner 
has been updated.  
Footnote c has been removed.  
To remain consistent with the 
Phase 3 rozanolixizumab clinical 
program. 
10.5 Appendix 5: Liver 
safety – suggested actions 
and follow-up assessments 
Table 10-3 
 
Clarification of language related to 
acetaminophen contribution to liver 
injury and removal of wording 
pertaining to requirements in 
China. 
The following reference was 
removed: 
James LP, Letzig L, Simpson PM, 
Capparelli E, Roberts DW, Hinson 
To remove wording that was left 
from a previous version and to 
clarify the language for suggested 
actions. a 
Updated to maintain consistency 
within the protocol. a 
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Section # and Name 
Description of Change 
Brief Rationale 
JA, et al. Pharmacokinetics of 
acetaminophen-protein adducts in 
adults with acetaminophen 
overdose and acute liver failure. 
Drug Metab Dispos. 2009; 
37:1779-84 
10.7, Appendix 7: 
Country-specific 
requirements 
New wording on specific 
requirements for France have been 
included. 
Updated in accordance with 
include local requirements. b 
10.7, Appendix 7: 
Country-specific 
requirements 
New wording on specific 
requirements for Japan have been 
added, including section-specific 
updates and new wording on 
specific requirements for AEs, 
ADEs, SAEs, SADEs, and Device 
Deficiencies associated with an 
investigational/medical device, 
have been added. 
In accordance with local 
requirements and actual condition 
of medical care, as well as sponsor 
requirements and procedures for 
any study using a medical or 
investigational device. a  
10.9 Appendix 9: 
Abbreviations and 
trademarks 
Additional abbreviations and 
definitions were added: ADE, PEX 
and SADE. 
Updated to reflect the parameters 
measured in the study. a 
10.11, Appendix 11: 
ITP-PAQ 
Removed an additional version of 
the ITP-PAQ questionnaire. 
Updated to remove an additional 
version of the questionnaire that 
was accidentally included. a 
10.13, Appendix 13: 
FATIGUE-PRO Physical 
Fatigue scale 
The "Physical Fatigue Instrument" 
has been replaced by the 
"FATIGUE-PRO Physical Fatigue 
scale.” 
Updated name for PRO.  
10.20, Appendix 20: 
Management of headaches 
Text added to clarify that the 
Headache Questionnaire should be 
completed by an HCP via an 
interview with the study 
participant, and treatment may be 
temporarily put on hold if a study 
participant experiences an AE of a 
severe headache that is considered 
related to the IMP in the opinion of 
the investigator, and is not resolved 
prior to the next scheduled IMP. 
To add further clarity. 
10.21, Appendix 21: 
Management of diarrhea 
Definition of severe (grade 3) 
diarrhea has been updated. 
Modification of language regarding 
stool sample collection for 
participants reporting severe 
diarrhea. 
To add further clarity.  
 
To clarify when stool samples may 
be collected. a 
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Section # and Name 
Description of Change 
Brief Rationale 
10.22 Appendix 22: 
Management of Infections 
and 
Hypogammaglobulinemia 
Modification of language regarding 
the Medical Monitor to clarify they 
may be unblinded. a 
Additionally, the following has 
been included in reference to study 
sites and study team: “remain 
blinded to IgG levels until after the 
first two dose of IMP.”  
In the event of a nonserious 
infection, the unblinded or blinded 
(after the second dose of IMP) 
medical monitor may be consulted.  
The following sentence was 
modified to include "must": 
Treatment must be temporarily 
discontinued for a study participant 
who develops an event of 
hypogammaglobulinemia with a 
serum total IgG of <1g/L 
irrespective of infection. 
Updated to be consistent across the 
Phase 3 rozanolixizumab clinical 
program. 
10.23 Appendix 23: 
Management of infusion 
reactions or 
hypersensitivity reactions 
Modification of language regarding 
potential infusion related reactions. 
Updated to provide further clarity. 
10.24 Appendix 24: SIAQ 
(infusion version) 
A new appendix to include 
examples of the SIAQ 
questionnaires has been added.   
Included for additional clarity and 
details on the questionnaire.  
11 References  
A new reference specific to SIAQ 
has been included.  
General update. 
a This update was previously incorporated to local protocol amendment 0.1 (Japan) 
b This update was previously incorporated to local protocol amendment 0.2 (France)  
 
11 
REFERENCES 
Anderson CL, Chaudhury C, Kim J, Bronson CL, Wani MA, Mohanty S. Perspective - FcRn 
transports albumin: relevance to immunology and medicine. Trends Immunol. 2006;27(7):343-8. 
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002. 
Keininger D and Coteur F. Assessment of self-injection experience in patients with rheumatoid 
arthritis: psychometric validation of the Self-Injection Assessment Questionnaire (SIAQ). Health 
Qual Life Outcomes. 2011;9:2. 
Mathias SD, Bussel JB, George JN, McMillan R, Okano GJ, Nichol JL. A disease-specific 
measure of health-related quality of life for use in adults with immune thrombocytopenic 
purpura: its development and validation. Health Qual Life Outcomes. 2007;5:11. 
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Page 198 of 199 
Mathias SD, Gao SK, Rutstein M, Snyder CF, Wu AW, Cella D. Evaluating clinically 
meaningful change on the ITP-PAQ: preliminary estimates of minimal important differences. 
Curr Med Res Opin. 2009;25(2):375-83. 
Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-
based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-207. 
Rodeghiero F, Michel M, Gernsheimer T, et al. Standardization of bleeding assessment in 
immune thrombocytopenia: report from the International Working Group. Blood. 
2013;121(14):2596-606. 
Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 
2007;7(9):715-25. 
Sampson HA, Muñoz-Furlong A, Campbell RL, 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. 
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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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Approval Signatures
Name:
tp0004-protocol-amendment-4
Version:
1. 0
Document Number:
CLIN-000186061
Title:
tp0004-protocol-amendment-4
Approved Date:
04 Apr 2022
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 04-Apr-2022 13:24:45 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 04-Apr-2022 13:40:42 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 04-Apr-2022 14:05:09 GMT+0000
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SAP_001.pdf: 
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21Oct2022 
Statistical Analysis Plan                            Rozanolixizumab                                                           
TP0004 
 
 
 
Confidential 
Page 1 of 76 
  
STATISTICAL ANALYSIS PLAN 
 
AMENDMENT 1 
Study: TP0004 
Product: Rozanolixizumab 
 
AN OPEN-LABEL EXTENSION STUDY TO INVESTIGATE THE 
LONG-TERM SAFETY, TOLERABILITY, AND EFFICACY OF 
ROZANOLIXIZUMAB IN STUDY PARTICIPANTS WITH 
PERSISTENT OR CHRONIC PRIMARY IMMUNE 
THROMBOCYTOPENIA (ITP) 
 
 
SAP/Amendment Number Date 
Final SAP 
01 Nov 2021 
Amendment 1 
21 Oct 2022 
  
 
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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Statistical Analysis Plan                            Rozanolixizumab                                                           
TP0004 
 
 
 
Confidential 
Page 2 of 76 
TABLE OF CONTENTS 
TABLE OF CONTENTS ........................................................................................................... 2 
1 
INTRODUCTION ........................................................................................................... 10 
2 
PROTOCOL SUMMARY ............................................................................................... 10 
2.1 
Study objectives ........................................................................................................... 10 
2.1.1 
Primary objective ................................................................................................. 10 
2.1.2 
Secondary objectives ........................................................................................... 10 
2.1.3 
Exploratory objectives ......................................................................................... 10 
2.2 
Study endpoints ............................................................................................................ 11 
2.2.1 
Primary endpoints ................................................................................................ 11 
2.2.1.1 
Primary safety endpoints ........................................................................... 11 
2.2.1.2 
Other safety endpoints ............................................................................... 11 
2.2.2 
Secondary endpoints ............................................................................................ 12 
2.2.2.1 
Secondary efficacy endpoint ..................................................................... 12 
2.2.2.2 
Other efficacy endpoints ........................................................................... 12 
2.2.2.3 
Other secondary endpoints ........................................................................ 12 
2.2.3 
Exploratory endpoints .......................................................................................... 12 
2.2.3.1 
Exploratory efficacy endpoints (First Exposure Participants only) .......... 12 
2.2.3.2 
Pharmacodynamic endpoints ..................................................................... 12 
2.2.3.3 
Pharmacokinetic endpoints ........................................................................ 13 
2.2.3.4 
Other exploratory endpoints ...................................................................... 13 
2.3 
Study design and conduct ............................................................................................ 13 
2.4 
Determination of sample size ....................................................................................... 14 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 14 
3.1 
General presentation of summaries and analyses ........................................................ 14 
3.2 
General study level definitions .................................................................................... 16 
3.2.1 
Analysis time points ............................................................................................ 16 
3.2.1.1 
Relative day ............................................................................................... 16 
3.2.2 
Study periods ....................................................................................................... 16 
3.2.3 
Mapping of assessments performed at Early Withdrawal Visit .......................... 17 
3.2.4 
Definitions Regarding the Dosing Regimen ........................................................ 17 
3.2.5 
General Considerations for Exploratory Arm Participants .................................. 17 
3.3 
Definitions of Baseline values ..................................................................................... 17 
3.4 
Protocol deviations....................................................................................................... 18 
3.5 
Analysis sets................................................................................................................. 18 
3.5.1 
Enrolled Set (ES) ................................................................................................. 18 
3.5.2 
Safety Set (SS) ..................................................................................................... 18 
3.5.3 
Pharmacokinetic Per-Protocol Set (PK-PPS) ...................................................... 18 
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3.6 
Center pooling strategy ................................................................................................ 18 
3.7 
Coding dictionaries ...................................................................................................... 18 
3.8 
Changes to protocol-defined analyses ......................................................................... 18 
4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 20 
4.1 
Handling of dropouts or missing data .......................................................................... 20 
4.1.1 
Handling of missing data for the primary safety endpoints ................................. 20 
4.1.2 
Handling missing data for the secondary endpoints ............................................ 20 
4.1.3 
Missing Data due to COVID-19 .......................................................................... 20 
4.1.4 
Dates and times .................................................................................................... 20 
4.2 
Handling of repeated and unscheduled measurements ................................................ 23 
4.3 
Handling and definition of the Corticosteroid (CS) prednisone equivalent dose ........ 23 
4.4 
Data Monitoring ........................................................................................................... 24 
4.5 
Multicenter studies ....................................................................................................... 25 
4.6 
Examination of subgroups ........................................................................................... 25 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 25 
5.1 
Subject disposition ....................................................................................................... 25 
5.2 
Protocol deviations....................................................................................................... 26 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 26 
6.1 
Demographics .............................................................................................................. 26 
6.2 
Other Baseline characteristics ...................................................................................... 27 
6.2.1 
Baseline disease characteristics ........................................................................... 27 
6.2.2 
Lifestyle ............................................................................................................... 28 
6.3 
Previous and ongoing medical history ......................................................................... 28 
6.4 
Procedure history and concomitant medical procedures ............................................. 29 
6.5 
Concomitant medications............................................................................................. 29 
Table 6-1: 
Concomitant Medications Classification ..................................................... 30 
6.5.1 
Assignment of medications to treatment period .................................................. 30 
6.6 
Prohibited concomitant medications and rescue medication ....................................... 31 
6.6.1 
Prohibited concomitant medication ..................................................................... 31 
6.6.2 
Rescue Therapy ................................................................................................... 31 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 31 
8 
SAFETY ANALYSES ..................................................................................................... 31 
8.1 
Statistical analysis of the primary safety endpoints ..................................................... 31 
8.1.1 
Estimand Details and Attributes to be considered for the evaluation of the 
primary endpoints ................................................................................................ 31 
8.2 
Adverse events ............................................................................................................. 32 
8.2.1 
Data considerations .............................................................................................. 32 
8.2.2 
Adverse Event Summaries ................................................................................... 33 
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8.3 
Vital Signs, Physical Findings, and Other Observations Related to Safety................. 35 
8.3.1 
Vital Signs and Physical Findings ....................................................................... 35 
8.4 
12-lead Electrocardiograms (ECG) .............................................................................. 35 
8.5 
Clinical Safety Laboratory Assessments ..................................................................... 36 
8.5.1 
Potential Drug-Induced Liver Injury ................................................................... 37 
8.6 
Extent of exposure ....................................................................................................... 37 
8.7 
Concentrations of Total Protein & Albumin ................................................................ 40 
8.8 
Serum and Plasma Complement Levels ...................................................................... 40 
8.9 
Other Safety Variables ................................................................................................. 40 
8.9.1 
Physical examination ........................................................................................... 40 
8.9.2 
Pregnancy testing ................................................................................................. 40 
8.9.3 
Childbearing potential ......................................................................................... 40 
8.9.4 
Assessment and management of Tuberculosis .................................................... 40 
8.9.5 
COVID-19 Impact ............................................................................................... 40 
9 
EFFICACY ANALYSES ................................................................................................ 40 
9.1 
Statistical analysis of the secondary efficacy endpoints .............................................. 41 
9.1.1 
Stable Clinically Meaningful Response ............................................................... 41 
9.1.2 
Change from Baseline to Week 53 or 55 for ITP-PAQ Symptoms domain score41 
9.2 
Statistical analysis of the other efficacy endpoints ...................................................... 42 
9.2.1 
Mean Change from Baseline in platelet count at each visit ................................. 42 
9.2.2 
Clinically Meaningful Response at each visit ..................................................... 43 
9.2.3 
ITP-BAT bleeding events and severity by visit ................................................... 43 
10 PHARMACOKINETICS (PK) AND PHARMACODYNAMICS (PD) ........................ 44 
10.1 
Pharmacokinetic endpoints .......................................................................................... 44 
10.1.1 
Plasma Concentration of Rozanolixizumab ......................................................... 44 
10.2 
Antidrug Antibodies (ADA) ........................................................................................ 45 
10.3 
Pharmacodynamic endpoints ....................................................................................... 49 
10.3.1 
Change from Baseline in Total Serum IgG concentration over time .................. 49 
10.3.2 
Change from Baseline in IgG subclasses concentration over time ...................... 49 
10.3.3 
Serum IG concentrations (IgA, IgE, IgM) over time ........................................... 49 
10.4 
Influence of Rozanolixizumab on vaccination titers ................................................... 49 
10.4.1 
Vaccination titers against Streptococcus pneumoniae, Neisseria meningitidis, 
and Haemophilus influenzae in splenectomized study participants .................... 49 
10.5 
Effect of Rozanolixizumab on post-vaccination biomarker(s) in study participants 
who received COVID-19 Vaccine ............................................................................... 49 
11 OTHER ANALYSES ...................................................................................................... 50 
11.1 
Statistical analysis of other endpoints .......................................................................... 50 
11.1.1 
Effect of Rozanolixizumab on study participant perceived symptoms ............... 50 
11.1.1.1 
ITP-PAQ V1 Domain Score ...................................................................... 50 
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11.1.2 
Reduction in use of steroids in study participants ............................................... 50 
11.1.2.1 
Percent change in oral steroid dose over time ........................................... 50 
11.1.2.2 
Change in dose and/or frequency of concomitant ITP medications .......... 50 
11.2 
Statistical analysis of other exploratory endpoints ...................................................... 50 
11.2.1 
Effect of Rozanolixizumab on Patient Reported Outcomes (PRO)  .................... 50 
11.2.1.1 
FATIGUE-PRO physical fatigue score ..................................................... 50 
11.2.1.2 
Patient Global Impression of Severity (PGI-S) ......................................... 50 
11.2.1.3 
Patient Global Impression of Change (PGI-C) .......................................... 51 
11.2.2 
Effect of Rozanolixizumab on Health-Related Quality of Life (HRQoL) .......... 51 
11.2.2.1 
European Quality of Life-5 Dimensions, 5 Levels Assessment 
(EQ-5D-5L) ............................................................................................... 51 
11.2.2.2 
Short form 36-item (SF-36) domain and composite scores....................... 51 
11.2.3 
Resource Utilization ............................................................................................ 52 
11.2.4 
Experience with the Subcutaneous self-administration ....................................... 52 
11.3 
Specific analyses for Pharmaceuticals and Medical Devices Agency (PMDA).......... 52 
11.4 
Headache Questionnaire .............................................................................................. 52 
12 REFERENCES ................................................................................................................ 52 
13 APPENDICES ................................................................................................................. 53 
13.1 
AE of focus for the Rozanolixizumab Program ........................................................... 53 
13.2 
Laboratory assessments – Marked abnormality criteria .............................................. 56 
13.2.1 
Hematology .......................................................................................................... 56 
13.2.2 
Chemistry ............................................................................................................. 58 
13.3 
Vital sign assessments - abnormal ............................................................................... 59 
13.4 
Electrocardiogram (ECG) – Abnormal ........................................................................ 59 
13.5 
ITP-PAQ Scoring ......................................................................................................... 59 
13.5.1 
ITP-PAQ Scales ................................................................................................... 59 
13.6 
ITP bleeding score ....................................................................................................... 61 
13.7 
Classification of the SF-36v2 questionnaire ................................................................ 72 
14 AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP) ...................... 73 
14.1 
AMENDMENT 1......................................................................................................... 73 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ..................................................... 76 
 
LIST OF TABLES 
Table 4‒1: 
Calculation rules for duration of AEs .............................................................. 21 
Table 4-2: 
Prednisone equivalent doses of systemic corticosteroids/steroids ................... 24 
Table 6-1: 
Concomitant Medications Classification ......................................................... 30 
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Table 8-1: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of the primary endpoint .................................. 32 
Table 8-2: Laboratory criteria for pDILI ................................................................................. 37 
Table 8-3: TP0004 dose levels and weight tiers of rozanolixizumab ...................................... 39 
Table 9-1: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of the secondary efficacy endpoint ................ 41 
Table 9-2: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of Change from Baseline to Week 53 or 55 
for ITP-PAQ Symptoms domain score ............................................................ 42 
Table 9-3: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of Mean Change from Baseline in platelet 
count at each visit............................................................................................. 43 
Table 9-4: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of Clinically Meaningful Response at each 
visit ................................................................................................................... 43 
Table 9-5: ITP-specific Bleeding Assessment Tool (ITP-BAT) Domains and categories ...... 43 
Table 10-1: Terms and Definitions for ADA Status Evaluation in Study Participants ........... 47 
Table 13-1: Following Events are Adverse Event of focus For Rozimab for All 
Indications and for ITP-specific Events:.......................................................... 53 
Table 13-2: Hematology Parameters ....................................................................................... 56 
Table 13-3: Chemistry Parameters........................................................................................... 58 
Table 13-4: Vital Sign Parameters ........................................................................................... 59 
Table 13-5: ECG Parameters ................................................................................................... 59 
Table 13-6: ITP Questions ....................................................................................................... 59 
Table 13-7: ITP-BAT scoring .................................................................................................. 62 
Table 13-8: SF-36V2 Questions .............................................................................................. 72 
Table 14-1: Modifications and changes ................................................................................... 73 
 
 
 
 
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List of Abbreviations 
ADAs 
Antidrug antibodies 
AEOF 
Adverse Events of Focus 
AESI 
Adverse Events of Special Interest 
AESM 
Adverse Events of Special Monitoring 
BLQ 
Below the limit of quantification 
BP 
Blood pressure 
CP 
Confirmed positive 
CSR               
Clinical Study Report 
CV                   
Coefficient of variation 
DEM 
Data Evaluation Meeting 
DNA 
Deoxyribonucleic acid  
eCRF 
Electronic Case Report Form 
ECG              
Electrocardiogram 
EOS 
End of Study  
EQ-5D-5L 
European Quality of Life-5 Dimension 5 Level 
Assessment 
ES                   
Enrolled Set 
EW 
Early withdrawal  
FDA 
Food and Drug Administration 
geoCV          
Geometric coefficient of variation 
geoMean        
Geometric mean 
hCG            
Human Chorionic Gonadotropin 
HLT             
High level term 
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HRQoL 
Health-related quality of life 
ICH              
International Council for Harmonisation  
IDMC              
Independent Data Monitoring Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IMP             
Investigational medicinal product 
ITP              
Primary immune thrombocytopenia 
ITP-BAT       
ITP-specific Bleeding Assessment Tool 
ITP-PAQ 
ITP-Patient Assessment Questionnaire 
LLOQ          
Lower limit of quantification 
MAP 
Managed Access Program 
MCS 
Mental Component Summary 
MedDRA         
Medical Dictionary for Regulatory Activities 
n                    
Number of participants 
NCP              
Not confirmed positive 
OLE 
Open Label Extension 
PCS 
Physical Component Summary 
PD               
Pharmacodynamic 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PK               
Pharmacokinetic 
PK-PPS         
Pharmacokinetic Per Protocol Set 
PROs 
Patient reported outcomes 
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PT                
Preferred term 
RNA 
Ribonucleic acid  
RZL 
Rozanolixizumab 
SAP             
Statistical Analysis Plan 
SC                
Subcutaneous 
SD               
Standard deviation 
SFU 
Safety Follow-up  
SF-36 V2 
Short form 36-item  
SIAQ 
Self-Injection Assessment Questionnaire 
SOC           
System organ class 
SS               
Safety Set 
TEAE           
Treatment-emergent adverse event 
TEMA          
Treatment-emergent markedly abnormal 
TFLs          
Tables, figures, and listings 
TPO 
Thrombopoietin 
TPO-RAs 
Thrombopoietin-receptor agonists  
ULN            
Upper limit of normal 
 
 
 
 
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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 statistical analyses of study TP0004. It also defines the summary tables, figures 
and listings (TFLs) to be included in the final Clinical Study Report (CSR) according to the 
protocol. 
This SAP is based upon, and assumes familiarity with, the following documents: 
Protocol Amendment 4: 04 Mar 2022 
DMC Charter: 26 Apr 2021  
The dosing regimen in the Original Protocol and Protocol Amendment 1 requiring a 
 
administration of IMP was modified with Protocol Amendment 2: the IMP administration was 
changed to 
 Protocol Amendment 2 was not submitted to any regulatory authorities prior 
to issuance of Protocol Amendment 3. 
After Protocol Amendment 3 was approved by the regulatory authorities, Protocol Amendment 4 
was issued for correcting errors and inconsistencies from Protocol Amendment 3. Further details 
can be found in this SAP. All data will be analyzed based on the visits identified per the 
Schedule of Activities in the protocol that participant was enrolled in at the time of the 
assessment. 
At the time this SAP was written, the sponsor had decided to terminate the parent studies 
TP0003 and TP0006 and consequently decided to terminate the TP0004 study prematurely by 30 
December 2022.  
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP may be amended accordingly. The content of this SAP is compatible with 
the International Council for Harmonization (ICH) E9 Guidelines. 
UCB is the Sponsor and PAREXEL is the Contract Research Organization (CRO) for this study. 
Note: The term Investigational Medical Product (IMP), study medication, and study drug are 
used interchangeably in this document. 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
To assess the long-term safety and tolerability of treatment with rozanolixizumab. 
2.1.2 
Secondary objectives 
• To assess the long-term clinical efficacy of treatment with rozanolixizumab 
• To assess the effect of rozanolixizumab on study participant perceived symptoms 
• To assess the reduction in use of steroids and other concomitant ITP medications 
2.1.3 
Exploratory objectives 
• To assess the effect of rozanolixizumab on patient-reported outcomes (PROs) 
• To assess the clinical efficacy of rozanolixizumab in study participants with first exposure to 
rozanolixizumab 
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• To assess effect of rozanolixizumab on health-related quality of life (HRQoL) and broader 
disease impact 
• To assess resource utilization 
• To assess the experience with the subcutaneous (sc) self-administration 
• To assess the PD effect of rozanolixizumab 
• To evaluate the incidence and emergence of antidrug antibody (ADA) of rozanolixizumab  
• To assess the pharmacokinetics (PK) of rozanolixizumab administered by sc infusion 
• To evaluate clinical response following end of dosing 
• To assess the influence of rozanolixizumab treatment on vaccination titers 
• To assess the effect of rozanolixizumab on post-vaccination biomarker(s) in study 
participants who received the COVID-19 vaccine 
2.2 
Study endpoints 
2.2.1 
Primary endpoints 
2.2.1.1 
Primary safety endpoints  
• Occurrence of treatment-emergent adverse events (TEAEs) 
• Occurrence of TEAEs leading to permanent withdrawal of rozanolixizumab (i.e., study 
discontinuation) 
2.2.1.2 
Other safety endpoints  
• Occurrence of treatment-emergent adverse events of special monitoring (AESM) 
• Occurrence of serious TEAEs 
• Occurrence of treatment-related TEAEs 
• Vital sign change from Baseline (blood pressure [BP], body temperature, and pulse rate) at 
each scheduled assessment during Treatment and Safety Follow-Up (SFU) Periods 
• 12-lead electrocardiogram (ECG) change from Baseline at each scheduled ECG assessment 
visit 
• Laboratory change from Baseline (hematology, including coagulation parameters, clinical 
chemistry, and urinalysis) at each scheduled assessment during Treatment and SFU Periods 
• Changes from Baseline in concentrations of total protein and albumin  
• Changes from Baseline in serum (C3 and C4) and plasma (C3a and C5a) complement levels 
at each scheduled assessment during study (for study participants experiencing infusion or 
hypersensitivity reactions) 
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2.2.2 
Secondary endpoints  
2.2.2.1 
Secondary efficacy endpoint 
• Stable Clinically Meaningful Response, defined as Clinically Meaningful Response (ie, 
platelet count ≥50×109/L) without rescue therapy at ≥70% of the visits over the planned 52 
week Treatment Period starting at Week 4 
2.2.2.2 
Other efficacy endpoints 
• Stable Response defined as platelet count ≥30×109/L and absence of bleedingb without rescue 
therapy at ≥70% of the visits over the planned 52-week Treatment Period starting at Week 4  
• Cumulative number of weeks with Clinically Meaningful Response over the 52-week 
Treatment Period 
• Cumulative number of weeks with platelet counts ≥30x109/L over the planned 52-week 
Treatment Period 
• Duration of first Clinically Meaningful Response starting at Week 4 
• Mean Change from Baseline in platelet count at each visit 
• Use of rescue medication by visit 
• ITP specific Bleeding Assessment Tool (ITP-BAT) bleeding events and severity by visit 
2.2.2.3 
Other secondary endpoints 
• Change from Baseline to Week 53 for ITP-PAQ Symptoms domain score 
• AUC of the oral steroid dose over time  
• Change in dose and/or frequency of concomitant ITP medications (excluding corticosteroids) 
over time  
2.2.3 
Exploratory endpoints  
2.2.3.1 
Exploratory efficacy endpoints (First Exposure Participants only) 
• In study participants with first exposure to rozanolixizumab: Durable Clinically Meaningful 
Platelet Response of ≥50x109/L, for at least 4 out of 6 
 visits during Weeks 13-25 
(of the OLE)  
• In study participants with first exposure to rozanolixizumab: Time to first Clinically 
Meaningful Platelet Response of ≥50x109/L: time from starting treatment to achievement of 
first response of ≥50x109/L 
2.2.3.2 
Pharmacodynamic endpoints 
• ADA at each scheduled assessment 
• Total serum IgG (absolute value) and change from Baseline (absolute value and percentage) 
in serum IgG and in serum IgG subclass concentration at each scheduled assessment 
• Absolute value and change from Baseline (absolute value and percentage) in serum Ig 
concentrations (IgA, IgE, IgM) at each scheduled assessment  
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2.2.3.3 
Pharmacokinetic endpoints 
• Plasma concentrations of rozanolixizumab at each scheduled assessment 
2.2.3.4 
Other exploratory endpoints 
• Change from Baseline in FATIGUE-PRO Physical Fatigue Score  
• Change from Baseline in Patient Global Impression of Severity (PGI-S) 
• Patient Global Impression of Change (PGI-C) at all available post-Baseline assessments  
• Change from Baseline in ITP-Patient Assessment Questionnaire (ITP-PAQ) domain scores 
• Change from Baseline  in European Quality of Life (EuroQol)-5 dimension 5 Levels 
Assessment (EQ-5D-5L) item responses 
• Change from Baseline in Short-Form 36-Item (SF-36) domain and composite scores 
• Number and length of hospitalizations 
• Number of infusion center admissions 
• PRE-Self Injection Assessment Questionnaire (SIAQ) (Infusion version) domains scores 
before the first sc self-administration in participants that self-administer  
• POST-SIAQ (Infusion version) domains scores at each available visit in participants that 
self-administer 
• Platelet count by visit after end of dosing 
• Time from end of rozanolixizumab dosing to loss of clinically relevant response 
• Percent change from Baseline in vaccination titers against Streptococcus pneumoniae, 
Neisseria meningitidis, and Haemophilus influenzae in splenectomized study participants 
• Change in post-vaccination biomarker(s) over time in study participants who received the 
COVID-19 vaccine 
2.3 
Study design and conduct 
 This is a Phase 3, multicenter, 59-week OLE study of rozanolixizumab in study participants 
with persistent or chronic primary ITP. Study participants from TP0003 and TP0006 who have 
completed the 24-week Treatment Period (irrespective of rescue therapy) and continue to meet 
the eligibility criteria will be offered enrollment into TP0004.  
This study will assess whether continued dosing 
 with rozanolixizumab is safe and well 
tolerated. This study will also assess whether continued rozanolixizumab sc infusions 
 over a 
period of 52 weeks will maintain a durable Clinically Meaningful Platelet count of ≥50×109/L. 
The rollover from TP0003 or TP0006 to TP0004 needs to be completed within 3 days after 
Week 25 (Visit 27) of the parent studies at the latest. In case of a late rollover, platelet counts 
will need to be remeasured. 
On Day 1 (Baseline Visit), which corresponds to Week 25 of the parent studies, TP0003 or 
TP0006, all study participants will enter TP0004. The study participants assigned to 
rozanolixizumab during the parent study will receive rozanolixizumab treatment 
 at the 
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assigned dose level at the end of TP0003 or TP0006, if the platelet count was between 
≥50×109/L and ≤150×109/L. If outside of this range, a higher or lower dose level than the final sc 
infusion in TP0003 or TP0006 is permitted according to Table 4-2 and Figure 4-1 (in the 
Protocol). Study participants previously randomized to placebo, will enter the study and begin 
rozanolixizumab treatment on the assigned (placebo) dose level received at the end of the parent 
studies; thereafter doses can be adjusted if platelets are outside the targeted range. 
Rozanolixizumab will be administered 
 as a sc infusion to maintain platelet count 
≥50×109/L. Dose levels equivalent to 
 and 
 total dose 
(corresponding to an average 
 dose in a participant weighing 70kg) 
 can be utilized 
for maintenance treatment.  
If treatment with rozanolixizumab does not lead to an increase in platelet counts ≥30×109/L, 
study participants can be treated with rescue therapy if deemed needed by the investigator. If 
platelet counts are ≥10×109/L to <30×109/L or active bleeding, rescue therapy is recommended 
(e.g., commercially available medication, such as intravenous immunoglobulin (IVIg), high dose 
corticosteroids and pulse steroids, platelet transfusions, or any other medication listed in 
Section 6.4.3 in the Protocol). If platelet counts are <10×109/L, rescue therapy is highly 
recommended as per Section 6.4.3. 
An external Independent Data Monitoring Committee (IDMC) will be utilized to review the 
safety data at predefined intervals and ad hoc as needed, should any emerging safety concern 
arise during the study. Key safety data may be pooled at the discretion of the IDMC for 
protection of all study participants if warranted. 
Based on feedback from the IDMC, 
 dosing was introduced in protocol amendment 2. 
Study participants being treated with the 
 dosing regimen were switched to the 
 
dosing regimen once protocol amendment 3 was approved at the respective study site.  
Additionally, the sponsor’s Safety Signal Detection Team will perform aggregated safety data 
reviews at predefined intervals across the rozanolixizumab program.  
Based on the number of study participants planned for the parent studies, up to a maximum of 
180 study participants who complete TP0003 or TP0006 may be eligible to enroll in this OLE 
study. 
2.4 
Determination of sample size 
No formal sample size calculation can be performed. All participants from the parent studies 
(TP0003 and TP0006) interested and eligible for the OLE will be included. It is expected that up 
to a maximum of 180 participants will be included.  
Note: Due to the premature termination of the study, only 43 participants did enroll into the OLE 
study. 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical analysis and generation of tables, figures, participant data listings, and statistical 
output will be performed using SAS® Version 9.4 or higher (SAS Institute, Cary, NC, USA).  
All tables, figures and listings will use Courier New font size 9. 
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Descriptive statistics will be displayed to provide an overview of the study results. For 
continuous variables, descriptive statistics will include number of participants with available 
measurements (n), mean, standard deviation (SD), median, minimum, and maximum.  
For categorical variables, the number and percentage of participants in each category will be 
presented. Unless otherwise noted, the denominator for percentages will be based on the number 
of participants included in the respective analysis set. Participants with missing data can 
generally be accounted for using the following approaches: 
• For summaries of demographics and Baseline characteristics: summarize percentages based 
on all participants in the analysis set and include a “Missing” category (corresponding to 
participants with missing data for the variable being summarized) as the last row in the list of 
categories being summarized.  
• For summaries of efficacy and safety variables, unless otherwise specified: summarize 
percentages based only on those participants with observed data for the variable being 
summarized. As the denominator may be different from the number of participants in the 
analysis set being considered, the denominator should be displayed in the table. The general 
format for displaying this will be “n/Nsub (%).” 
Unless otherwise noted, all percentages will be displayed to one decimal place. No percentage 
will be displayed for zero counts, and no decimal will be presented when the percentage is 100%.  
Tables which contain no data as no subject have met the criteria will display "No participants 
have met the criteria.” 
For the purpose of the tabulations the lower and upper confidence limits for the percentages will 
be truncated at 0 and 100% respectively. 
For PK concentrations, summary statistics will include geometric mean, geometric coefficient of 
variation (CV), 95% confidence intervals (CIs) for geometric mean, arithmetic mean, SD, 
median, minimum, and maximum. All summaries of PK variables will be based on the observed 
values. No imputation will be used. 
Decimal places for descriptive statistics will always apply the following rules: 
• “n” will be an integer 
• Mean, SD, and median will use one additional decimal place compared to the original data 
• CV [%] will be presented with one decimal place 
• Minimum and maximum will have the same number of decimal places as the original value. 
If no participants have data at a given time point, for example, then only n=0 will be presented. 
However, if n<3, present the n, minimum and maximum only. If n=3, n, mean, median, 
minimum, and maximum will be presented only. The other descriptive statistics will be left 
blank. 
Derived variables in general will display the mean, SD and median to 1 more decimal place than 
the variables used in the derivation. If the number of decimal places reported in the raw data is 
varied, then use either the maximum raw number of reported decimal places or 3, whichever is 
the lowest, as a guide for the descriptive statistics.  
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3.2 
General study level definitions 
3.2.1 
Analysis time points 
All data will be analyzed based on the visits identified per the Schedule of Activities in the 
protocol that participant was enrolled in at the time of the assessment. 
Mapping to visit windows will not be applied.  For Early Withdrawal visits refer to Section 3.2.3  
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 
which will occur at Baseline (Day 1) 
Relative days for an event or measurement occurring before the date of first sc infusion will be 
prefixed with '-' and 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 first 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 participant data listing. In such cases, relative day should be presented as ‘- -’ 
in the participant data listings. 
3.2.2 
Study periods 
As detailed in the Schedule of Activities in the Protocol, the following study periods are defined 
for this trial: 
• Treatment Period: Starts on the day of the first dose administration of study drug (Day 1) 
and ends after the Week 53 or Week 55 visit assessments (or at the EW Visit for study 
participants withdrawn from the study before the Week 53 or 55 visit), depending on the 
protocol in place at the time final assessments were performed.  
• Safety Follow-up Period (SFU): Starts with last dose administered and ends 8 weeks after 
final dose administered. 
A study participant is considered to have completed the study if he/she has completed both the 
Treatment and Safety Follow-up Periods of the study including the SFU Period. 
A study participant will be said to have completed the SFU period if she/he had completed the 
last scheduled visit in the SFU period.  
Study participants will have an EOS Visit performed 8 weeks after the final dose of IMP (unless 
they are enrolling in TP0009 at week 53 or 55), or upon discontinuation of the study. 
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3.2.3 
Mapping of assessments performed at Early Withdrawal Visit 
Early Withdrawal assessments will be assigned to the next scheduled site visit (following the last 
scheduled visit that the participant completed prior to EW). Only EW assessments will be 
performed on this mapped visit.   
3.2.4 
Definitions Regarding the Dosing Regimen 
Based on feedback from the IDMC, 
 dosing was introduced in protocol amendment 2. 
Study participants being treated with the 
 dosing regimen were switched to the 
 
dosing regimen once the protocol amendment 3 was approved at the respective study site.  
For the purpose of this SAP, presentation “by Dosing Regimen” refers to the presentation of 
assessments based on whether the participant was receiving 
 or 
 dosing of 
rozanolixizumab at the time the assessment or event occurred.  
As soon as Protocol Amendment 3 was approved at each site, the participants who started 
TP0004 on 
dosing and did not yet complete the treatment period, were allowed to 
either transition to 
 dosing or discontinue treatment (in accordance to Protocol 
Amendment 3 and subsequent versions).  
Summary tables and listings presented by timepoint will be separated by dosing regimen. 
Timepoint summaries will be split by whether the participant was receiving 
 or 
 
dosing at the time of the assessment (ie, took place before or after being dosed under Protocol 
Amendment 3) as applicable. All 
 dosing assigned visits will be presented before 
 dosing assigned visits. 
3.2.5 
General Considerations for Exploratory Arm Participants 
Based on the changes made in Protocol Amendment 2 and subsequent protocol versions of 
TP0004, the Exploratory Treatment portion of the study design has been removed. For 
participants who took part in the Exploratory Treatment Arm prior to the implementation of 
Protocol Amendment 3 (protocol amendment 2 was never implemented), only visits and 
assessments (scheduled and/or unscheduled) prior to the start of the Exploratory Treatment Arm 
(Visit 19, Week 25 of Protocol Amendment 1) will be included in the summaries and figures 
related to the analysis of the endpoints detailed in this SAP. All other visits and assessments (and 
corresponding data) collected after the start of the Exploratory Treatment Arm will be listed. 
3.3 
Definitions of Baseline values 
As stated in the Protocol, the Baseline Visit in TP0004 will correspond to the Week 25 of the 
parent studies (TP0003/TP0006). Baseline in TP0004 will be defined as the last available pre-
dose value prior to the first infusion of study drug in the TP0004 Treatment Period (i.e., Visit 
1/BL) unless otherwise stated. For the purpose of this SAP, Visit 1/BL refers to the nomenclature 
used in the Schedule of Activities (Table 1-1) in the Protocol, which is the equivalent to Baseline 
or Week 1 Day 1 in the eCRF.  
When applicable (as specified in Table 1-1 of the Protocol, and their corresponding SAP 
sections), data will be transferred from the Screening or Baseline Visit of TP0003/TP0006 for 
the following values: 
• Demographics 
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• Baseline Disease History 
Scheduled or unscheduled measurements can be used as the Baseline value. If an unscheduled 
measurement occurs after the planned baseline measurement time point but before dosing, then 
the unscheduled measurement will be used. 
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 safety, key efficacy, or PK/PD outcomes 
(if applicable) for an individual participant. 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 (ES) 
All study participants who have signed the informed consent. 
3.5.2 
Safety Set (SS) 
All study participants who received at least 1 dose of IMP (partial or full). Analysis of this set 
will be according to the treatment the participants actually received, and will be used for the  
efficacy, demographic, PK, and safety analyses. 
3.5.3 
Pharmacokinetic Per-Protocol Set (PK-PPS)  
A subset of the Safety Set, consisting of those study participants who received at least 1 dose and 
had at least 1 valid PK measurement and no important protocol deviations affecting the PK 
variable, as confirmed during a pre-analysis review of the data prior to database lock. 
3.6 
Center pooling strategy 
It is planned to recruit participants in North America, Europe, and Asia in this study, with 
possible extension to other regions and countries. The data from all sites will be pooled for 
analysis purposes using the following geographical regions: North America, Europe, Asia 
(excluding Japan), and Japan. 
3.7 
Coding dictionaries 
Adverse events (AEs) will be coded using version 24.0 or later of the Medical Dictionary for 
Regulatory Activities (MedDRA®).  
Medications will be coded according to version Mar2021 or later of the World Health 
Organization Drug Dictionary (WHODD). Medical procedures will not be coded. 
3.8 
Changes to protocol-defined analyses 
(1) Added COVID-19 as an intercurrent event to all endpoints 
(2) Change from Baseline will not be calculated for the following safety endpoints. Only raw 
data will be listed. 
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• Vital signs change from Baseline (blood pressure [BP], pulse rate, body temperature) at each 
scheduled assessment during Treatment and SFU Periods 
• 12-lead echocardiogram (ECG) change from Baseline at each scheduled ECG visit 
• Laboratory change from Baseline (hematology including coagulation parameters, clinical 
chemistry, and urinalysis) at each scheduled assessment during Treatment and SFU Periods  
• Change from Baseline in concentrations of total protein and albumin 
• Change from Baseline in serum complement levels (C3 and C4) and plasma complement 
levels (C3a and C5a) at each scheduled assessment during the study (for study participants 
experiencing infusion reactions or hypersensitivity reactions) 
• Absolute values and change from Baseline (absolute values and percentage) in serum 
immunoglobulin concentrations (IgA, IgE, IgM) at each scheduled assessment 
(3) No formal statistical analyses of efficacy endpoints will be conducted. Only the following 
secondary efficacy endpoint(s) will be summarized descriptively and listed: 
• Stable Clinically Meaningful Response - platelet count ≥50x109/L without rescue therapy at 
≥70% of the visits 
• Change from Baseline to Week 53 including all intermediate timepoints for ITP-PAQ 
Symptoms domain score 
(4) The following changes are made to endpoints 
• Remove “including all intermediate endpoints” in “Change from Baseline to Week 53 or 55 
for ITP-PAQ Symptoms domain score” and added “Week 55” 
• Add endpoint “Clinically Meaningful Response at each Visit” 
• “AUC of the oral steroid dose over time” changed to “Percent Change from Baseline in Oral 
Steroid Dose Over Time” and changed from secondary to “other” endpoint 
• “Change in dose and/or frequency of concomitant ITP medications (excluding 
corticosteroids) over time” Changed to “Percent Change from Baseline in Concomitant ITP 
Medications (excluding Corticosteroids) Over Time” and changed from secondary to “other” 
endpoint 
(5) Subgroup analyses to the secondary efficacy analysis will not be performed 
(6) Analysis for the PMDA on the Japanese subset of participants will not be performed 
(7) Change from baseline will not be calculated for the following endpoints. Only item responses 
will be listed. 
• Change from Baseline in European Quality of Life-5 Dimension 5 Levels (EQ-5D-5L) item 
responses  
• Change from Baseline in Short form 36-item (SF-36) domain and composite scores 
• Change from Baseline in the ITP-PAQ V1 domain Scores (except for Symptoms score) 
• Change from Baseline in FATIGUE-PRO Physical Fatigue Score by visit  
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• Change from Baseline in Patient Global Impression of Severity (PGI-S) 
(8) Percent change from Baseline will not be calculated for the following endpoint. Titers will be 
listed. 
• Percent change from Baseline in vaccination titers against Streptococcus pneumoniae, 
Neisseria meningitidis, and Haemophilus influenzae in splenectomized study participants 
(9) Definition of PK-PPS changed to “A subset of the Safety Set, consisting of those study 
participants who received at least 1 dose and had at least 1 valid PK measurement and no 
important protocol deviations affecting the PK variable, as confirmed during a pre-analysis 
review of the data prior to database lock.” 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Handling of dropouts or missing data 
4.1.1 
Handling of missing data for the primary safety endpoints 
The primary safety analysis is based on a “treatment policy” estimand to allow for the inclusion 
of study participants that receive rescue medication. Regardless of a participant’s initial dosing 
regimen at the start of TP0004 (
 or
 dosing), missing safety values will not be 
imputed; all available data will be reported.  
4.1.2 
Handling missing data for the secondary endpoints 
Study participants who have not met the threshold for Stable Clinically Meaningful Response 
will be imputed as non-responders for the analysis. Missing platelet data at any visit will be 
considered "worst case" and set to zero ("no response") for that specific visit. Missing data for 
the ITP PAQ instrument will not be imputed.  
For the secondary efficacy analysis, participants with intercurrent events will be considered as 
non-responders unless otherwise stated. 
Missing data strategy for PRO related endpoints will follow instructions indicated in each 
instrument. 
4.1.3 
Missing Data due to COVID-19 
For the purpose of this SAP, study participants who have visits impacted by COVID-19 for any 
reason [e.g., confirmed coronavirus disease (COVID-19) infection (e.g., signs/symptoms such as 
fever, cough, shortness of breath), or known exposure sufficient to necessitate testing or self-
imposed quarantine] will be imputed as non-responders for the analysis at the corresponding 
visit. Missing platelet count data due to COVID-19 will be considered worst case and set to zero 
(“no response”) for that specific visit.  
4.1.4 
Dates and times 
Partial and completely missing dates may be imputed for the following reasons: 
• Classification of Adverse events (AEs) as treatment-emergent 
• Classification of medications as prior or concomitant 
• Duration of AEs. 
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Imputed dates will not be shown in listings.  All dates will be displayed as reported in the 
database. 
The following rules will be applied for partial start dates: 
• If only start month and year are specified and are not the same as month and year of first 
dosing, then use the 1st of the month.  
• 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 only the year is specified, and the year of dosing is not the same as the year of the start date 
then use 01 Jan of the year of the start date.  
• 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 01 Jan 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 01 Jan).  
• 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 01 Jan 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 01 Jan).  
Any medication with a start date on the first dosing date unknown, will be assumed to be 
concomitant. 
The following rules will be applied for partial stop dates: 
• If only the month and year are specified, then use the last day of the month 
• If only the year is specified, then use December 31 of the known year 
• If the stop date is completely unknown, do not impute the stop date, except for ITP 
medications where end date is missing and ongoing is ticked as “no”, which will be imputed 
as “Past” medications. 
Table 4‒1: 
Calculation rules for duration of AEs 
Data 
availability 
Onset date 
Outcome 
date 
Calculation rules 
Complete data 
Analysis 
Start Date 
(D1) 
Analysis 
End Date 
(D2) 
Duration = (D2 – D1) + 1  day 
Start date 
missing 
-- 
D2 
Duration ≤ (D2 – D0) + 1 day 
Note: D0 = imputed dose start date per partial stop dates.  
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Data 
availability 
Onset date 
Outcome 
date 
Calculation rules 
End date 
partially or 
completely 
missing 
D1 
-- 
If end date is completely missing, then: 
For ongoing AE: 
Duration ≥ (Discharge Day – D1) + 1 day OR 
Duration ≥ (Data cut-off day) – D1 + 1 day 
For resolved AE: 
Duration ≤ (Discharge Day – D1) + 1 day OR 
Duration ≤ (Data Cut-Off Day) – D1 day 
 
Note: Where discharge refers to the date when the 
participant rolls over to TP0009, or the date of the 
end of study visit for completed participants or the 
date of discontinuation for participants that were 
withdrawn. 
 
If end date is partially missing, then: 
Duration = (D3 – D1) + 1 day 
Note: D3 is the imputed end date using partial stop 
dates (see above). 
For any AEs with known start date, if the end date is 
missing, the date of last contact will be used as the 
discharge day. 
For participants still ongoing in the study at the time of 
the data cut-off, and for whom no discharge date is 
available, the date of the data cut-off will be used instead 
of the discharge date. 
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Data 
availability 
Onset date 
Outcome 
date 
Calculation rules 
Start and end 
date missing 
partially or 
completely 
missing 
-- 
-- 
For ongoing AE: 
Duration ≥ (Discharge Day – D0) + 1 day OR 
Duration ≥ (Data cut-off day – D0) + 1 day 
For resolved AE: 
Duration ≤ (Discharge Day – D0) + 1 day OR 
Duration ≤ (Data Cut-Off Day – D0) + 1 day 
 
For a participant in the SS, D0 is the date of first 
administration of IMP, and for participants excluded from 
the SS, D0 is the date of signing the informed consent. 
Note: Discharge refers to the date of the end of study 
visit or the date of discontinuation for participants 
that were withdrawn. 
For any AEs with known start date after the date of 
discontinuation, the date of last contact will be used as 
the discharge day. 
For participants still ongoing in the study at the time of 
the data cut-off, and for whom no discharge date is 
available, the date of the data cut-off will be used instead 
of the discharge date.  
4.2 
Handling of repeated and unscheduled measurements 
All repeated and unscheduled measurements will be presented in the listings, where applicable. 
The following general rules will apply to all repeated and unscheduled measurements: 
• For repeated or unscheduled measurements obtained prior to the first dose of IMP the latest 
non-missing value (scheduled or unscheduled) will be used in the calculation of descriptive 
statistics (ie, Screening and/or Baseline) 
• For repeated or unscheduled measurements obtained at the designated Baseline visit, the 
latest non-missing value (scheduled or unscheduled) will be defined as the Baseline record 
that occurred prior to the first dose of IMP 
• For any scheduled measurement obtained at any time point after the first dose of IMP is 
missing, unscheduled measurements will not be used for any missing assessment. 
• See Section 8.4 for the rules applied to ECG triplicate measurements.  
4.3 
Handling and definition of the Corticosteroid (CS) prednisone 
equivalent dose 
For the purposes of further analysis and tabulations, all corticosteroid doses (including both prior 
and concomitant corticosteroids taken for any indication) will be converted to prednisone 
equivalent doses. The conversion table for systemic corticosteroids is presented in Table 4-2. 
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Systemic corticosteroids are those with a route of administration of oral, intravenous, or 
intramuscular. All others (including topical, ocular, nasal, subcutaneous, intraarticular, etc.) will 
be considered non-systemic steroids which will have a prednisone equivalent dose = 0mg/day. 
Budenoside is considered non-systemic even if taken orally and will always be assigned a 
prednisone equivalent dose = 0mg/day.  
The prednisone equivalent dose will be included in the listing.  
For example, if the total daily dose of triamcinolone is 8mg, the equivalent total daily dose of 
prednisone will be 10mg. If a new corticosteroid is reported that is not in Table 4-2, the 
appropriate prednisone equivalent conversion will be determined and the prednisone equivalent 
dose will be included in a separate systemic corticosteroids concomitant medication listing. 
If medications are available in ATC 2 code 
 which are not in table below, then the dose 
equivalent to 5mg/day Prednisone will be provided by the physician for this new system CS and 
the TFL footnote will be updated with this information for the newly identified CS 
Table 4-2: 
Prednisone equivalent doses of systemic corticosteroids/steroids   
Corticosteroids /Steroids 
Dose equivalent to  
5mg/day Prednisone 
Cortisone  
25 
Hydrocortisone  
20 
Deflazacort  
6.5 
Prednisone  
5 
Prednisolone 
Methylprednisolone  
5 
4 
Triamcinolone  
4 
Dexamethasone  
0.75 
Betamethasone  
0.6 
Notes:  
− 
All non-systemic corticosteroids (including topical, ocular, nasal, subcutaneous, intra articular, etc.) will be 
assigned a prednisone equivalent dose = 0 mg/day.  
− 
 "CORTICOSTEROIDS FOR SYSTEMIC USE, 
" 
4.4 
Data Monitoring  
An external IDMC will be established to review the safety data at predefined intervals and ad 
hoc as needed should emerging safety concerns arise during the study.  
Details of the IDMC composition, processes, and responsibilities will be documented in the 
IDMC charter. The IDMC will be the same as used for the parent studies TP0003 and TP0006, 
but data from each study will be presented separately. Key safety data may be pooled at the 
discretion of the IDMC for protection of all study participants if warranted. The IDMC will 
oversee the safety of the study by reviewing safety data at periodic data reviews. The IDMC will 
consist of members independent from UCB. Study enrollment will not be halted during planned 
IDMC review of the safety and efficacy data. The objectives and procedures for the IDMC will 
be detailed in the IDMC Charter. 
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After parent studies are completed, TP0004 will not have its own IDMC but will fall under the 
program-independent DMC (PiDMC) instead.  
4.5 
Multicenter studies 
This is a multicenter study; however, individual center’s results will not be presented.  
4.6 
Examination of subgroups  
Subgroups will no longer be examined. 
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
The following outputs will be created.  
Summaries: 
− Reasons for ineligibility (as collected on the Eligibility Criteria CRF page) will be 
summarized using the ES for all study participants who failed to meet eligibility criteria 
for TP0004. 
− Disposition of Study Participants Enrolled will be summarized using the ES for 
overall, by region and by site. In this summary, the site number, principal investigator 
name, first subject in date, last subject out date, will be captured by each analysis set 
(ES, SS, PK-PPS).  
− Disposition of Analysis Sets: summary of disposition of study participants by analysis 
sets (ES, SS, PK-PPS) using the ES. 
− Disposition and Discontinuation Reasons, using the ES will contain the number and 
percentage of study participants who: 
o Started study and started each study period (Treatment Period and SFU Period) 
o Completed the study / study period 
o Discontinued study / study period 
▪ Primary Reason for discontinuation (premature study termination as 
collected in the Study Termination CRF).  
- 
Discontinuation due to AEs, using the ES to tabulate the total number of study 
participants who discontinued the study due to AEs and the categories: AE serious fatal, 
AE non-fatal and other (AE non-serious, fatal). 
- 
COVID-19 Disposition:  Disposition and discontinuation reasons using the ES will 
contain the number and percentage of study participants (overall and by dosing regimen) 
who started, completed and permanently discontinued Treatment Period / Safety Follow-
Up Period overall and by pre-, during and post- COVID-19 pandemic based on the start, 
completed and discontinuation date relative to the pandemic cut-off date (20 March 2020 
start date, no end date). The discontinuation reason in each period will also be 
summarized. Discontinuation due to COVID-19 pandemic will be listed as sub-category 
under “Other” reason. 
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5.2 
Protocol deviations 
Important Protocol deviations will be summarized using the ES to include: 
Number and percentage of participants with: 
a. No important protocol deviations 
b. At least one protocol deviation in the following categories 
− Inclusion criteria  
− Exclusion criteria  
− Withdrawal criteria  
− Prohibited concomitant medication use 
− Incorrect treatment or dose 
− Treatment non-compliance  
− Procedural non-compliance 
c. Number of Participants excluded from the PK-PPS (and all categories in item b above). 
A by-study participant listing of important protocol deviations will be provided using the ES. 
Note:  The criteria for exclusion of study participants and/or study data from the PK-PPS will be 
defined in the Protocol Deviation Specification document. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
Unless otherwise specified, all summaries will be based on the ES.  
6.1 
Demographics 
Demographic variables collected at Screening or Baseline Visit, or Week 25 (Visit 28) of 
TP0003 or TP0006, as applicable, will be summarized on the ES using descriptive statistics, by 
categories mentioned below.  
Categories for continuous variables (including n, mean, SD, Median, Min and Max): 
• Age (years) - at the time of study entry 
• Weight (kg) 
• Height (cm) 
• BMI (kg/m2) calculated as: 𝐵𝑀𝐼= 
Weight (kg)
(Height (m))2 
Categorical variables (using frequency counts and percentages): 
• Age (18 - < 65, 65 - < 85, ≥ 85 years) 
• Age (≤ 18, 19 - < 65, ≥ 65 years)  
• BMI (< 25, 25 - < 30, ≥ 30 kg/m2) 
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• Weight (< 50kg, 50kg - < 70 kg, 70 - < 100kg, ≥ 100kg) 
• Gender (Male, Female) 
• Race (American Indian or Alaska native, Asian, Black or African American, Native 
Hawaiian or Other Pacific Islander, White, Other/Mixed) 
• Ethnicity (Hispanic or Latino, Not Hispanic or Latino) 
• Region (North America, Europe, Asia [excluding Japan], Japan) 
• Country 
• Parent study Where Participant Originated From: TP0003 or TP0006 
• First Time Exposed to RLZ (Rozanolixizumab) (Yes/No) 
By-study participant listings of demographics will be provided.  
Childbearing potential will be listed for the ES. 
6.2 
Other Baseline characteristics 
6.2.1 
Baseline disease characteristics  
The following will be summarized using descriptive statistics at baseline of the parent study 
unless stated otherwise (using ES): 
• Age at first ITP diagnosis (years) 
• Time since first confirmed diagnosis of ITP (years) (as collected in the eCRF) 
• Splenectomy (Yes/No) 
• IgG level (g/L) for 
− Non-splenectomized participants 
− Splenectomized participants 
• Platelet count (x109/L) (as collected in the eCRF) 
• Degree of thrombocytopenia (platelet count < or ≥15x109/L) (using data collected in the 
eCRF)  
• ITP Duration (persistent or chronic primary ITP at time of enrolment into parent study, as 
defined in Section) 
• Total Number of Prior Unique ITP Medications (as collected in Parent study eCRF) 
• Total Number of Prior ITP Medications (as collected in Parent study eCRF) 
• Number of past ITP Medications (as collected in Parent study eCRF)(1, 2, and  ≥3)   
• Concomitant use of TPO-RAs (e.g., Eltrombopag and Avatrombopag) (Yes/No) 
Notes:  
− Persistent or chronic primary ITP as defined in Section 2.3 
− Data will be summarized using data captured or derived from eCRF. 
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− The duration of ITP for chronic ITP participants will be computed in years and it will 
be calculated as follows: 
Date of Screening – Date of Diagnosis
365.25
 , where Date of Screening is from the parent study, and 
the date of diagnosis will be obtained from the ITP history eCRF page. 
− The duration of ITP – for persistent ITP participants will be computed in months and it 
will be calculated as : 
Date of Screening – Date of Diagnosis
30.5
 , where Date of Screening is from the parent study, and 
the date of diagnosis will be obtained from the ITP history eCRF page.  
− Age at diagnosis (years) will be calculated as: 
Date of diagnosis − Date of birth
365.25
 
− If the date of diagnosis is missing, the duration of disease and age at diagnosis will not 
be calculated. In the case of the start day being missing, the day will be imputed with 
the 1st of the month. In the case of the start day and month being missing, the date will 
be imputed with 01 January. 
The duration of ITP (years) will be calculated as follows, where Date of Screening is 
from the parent study, and the date of diagnosis will be obtained from the ITP history 
page of the eCRF:  
Date of screening – Date of Diagnosis
365.25
  
− The duration of ITP will be presented in the listings as follows: 
◦ 
In years to 1 decimal place for chronic primary ITP participants 
◦ 
In months (3-12) for persistent primary ITP participants 
− The definition of Past and Prior ITP medications for this summary refers to the 
definition outlined in Section 6.5. 
− Unique Prior ITP is derived as follows: 
◦ 
To derive prior ITP medications, see Section 6.5.   
◦ 
To derive unique: count all medications with ATC code 
 as one, count all 
medication with ATC code 
 as one, for remaining prior ITP medications count all 
unique standardized medication names (CMDECOD) 
6.2.2 
Lifestyle 
A listing of lifestyle for DILI CRFs (DILI patients only) data (alcohol use and illicit drug use in 
the past six months (yes/no)) will be created using the SS.  
6.3 
Previous and ongoing medical history  
Any medical conditions that were not reported in TP0003/TP0006 will be captured on eCRF of 
this study and listed using the ES. 
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6.4 
Procedure history and concomitant medical procedures 
Procedure history that was not reported in TP0003/TP0006, and concomitant medical procedures 
will be listed using the ES. 
6.5 
Concomitant medications  
Medications will be classified as follows based on imputed start and stop date & times as 
outlined in Section 4.1.3. For the following definitions, the first administration of IMP refers to 
first administration of IMP in TP0004, unless otherwise noted. 
Past Medications: defined as any medications that started and stopped before first 
administration of IMP. 
This includes medications reported in the following eCRF pages: 
- 
“ITP Treatment history”  
- 
“Prior and Concomitant Medications”, if end date before first IMP date 
- 
“Prior and Concomitant Medications ITP Treatment”, if end date before first IMP 
date. 
Prior Medications: defined as any medications that started before the first administration of 
IMP.  
This includes medications reported in the following eCRF pages: 
- 
“ITP Treatment History”,  
- 
“Prior and Concomitant Medications”, if start date before first IMP date. 
- 
“Prior and Concomitant Medications ITP Treatment”, if start date before first IMP 
date. 
Prior and Concomitant (Baseline) Medications: defined as any medications that started prior 
to first administration of IMP and stopped after the first administration of IMP (classified as 
prior and concomitant medications). This includes medications reported in the following eCRF 
pages: 
- 
“Prior and Concomitant Medications”, if start date before first IMP date and end date 
after first IMP date or ongoing 
- 
“Prior and Concomitant Medications ITP Treatment”, if start date before first IMP 
date and end date after first IMP date or ongoing 
Concomitant medications: defined as any medication that has been taken at least once after the 
first administration of IMP. 
This includes medications reported in the following eCRF pages: 
- 
“Prior and Concomitant Medications”, if end date after first IMP date or ongoing  
- 
“Prior and Concomitant Medications ITP Treatment”, if end date after first IMP date 
or ongoing 
Concomitant only medication: defined as any medication that started after first administration 
of IMP 
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This includes any medication reported in the following eCRF pages: 
- 
“Prior and Concomitant Medications”, if start date after first IMP date 
“Prior and Concomitant Medications ITP Treatment”, if start date after first IMP date. 
Table 6-1: Concomitant Medications Classificationbelow summarizes concomitant medication 
classification with details around medication start and finish. 
Table 6-1: Concomitant Medications Classification 
Medication Started 
Medication finished 
Classification 
Before 1st Dose IMP 
Before 1st Dose IMP 
Past 
Any time 
After 1st Dose IMP 
Concomitant  
After 1st Dose IMP 
After 1st Dose IMP 
Concomitant Only 
Before 1st Dose IMP 
After 1st Dose IMP 
Prior and Concomitant (Baseline) 
Before 1st Dose IMP     
Any time 
Prior Medications 
All the categories mentioned above will be summarized separately for ITP medications; Non-ITP 
medications will be listed only (using the ES) to display the number and percentage of 
participants in each category by Anatomical Therapeutic Chemical (ATC) class, presenting as 
Anatomical Main Group (ATC Level 1), Pharmacological Subgroup (ATC level 3), Preferred 
Term (PT). Concomitant and Concomitant Only medications will be summarized by dosing 
regimen. 
Any medications with missing dates and/or times will be handled as described in Section 4.1.2 to 
classify them as prior and/or concomitant. 
Listings for ITP and Non-ITP medications will be also produced using the ES. 
Note: WHODD Mar2021 will be used for ATC terms. 
6.5.1 
Assignment of medications to treatment period 
The following rules will be used to assign a concomitant medication to a study period: 
• Treatment Period: a medication is taken at least once between the first administration of 
IMP on Day 1 and 
 after the last dose of IMP (on Week 55) or the early withdrawal 
visit, for participants who were on 
 dosing at the end of the study. For participants 
who were on 
 dosing at the end of the study, the end date of the treatment period is  
 after the last dose of IMP, on Week 53. 
• Safety Follow-Up Period: A medication will be assigned to the Safety Follow-Up Period if 
it has been taken at least once from the day after the end of the Treatment Period up until the 
EOS visit. 
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6.6 
Prohibited concomitant medications and rescue medication 
6.6.1 
Prohibited concomitant medication 
All prohibited concomitant medication listed in Section 6.4.2 in the protocol, will be summarized 
using the number and percentage of study participants who received prohibited concomitant 
medication by ATC class, presenting ATC Level 1, ATC level 3, and PT, ordered alphabetically 
for the ATC class and in terms of decreasing frequency for PT within ATC class using the ES by 
dosing regimen and overall. In the event of ties, PT will be ordered alphabetically.  
6.6.2 
Rescue Therapy 
All rescue therapies mentioned in Section 6.4.3 in the protocol, identified if Rescue Medication 
is ticked as yes on eCRF, will be summarized using the ES.  
The number and percentage of study participants who received rescue medication will be 
displayed by ATC class, presenting ATC Level 1, ATC level 3, and PT (ordered alphabetically 
for the ATC class and in terms of decreasing frequency for PT within ATC class using the ES, 
overall and by dosing regimen. In the event of ties, PT will be ordered alphabetically. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
Not applicable. The number of infusions will be recorded as detailed in Section 8.6.  
8 
SAFETY ANALYSES 
All safety analyses will be presented separately using the SS, unless otherwise noted. Listings 
will be presented using the SS by participant; tabulations will be presented by Treatment and 
Safety Follow-Up Period (refer to Section 3.2.2 for study period definitions). Summaries by be 
presented by whether the assessment occurred while the participant was receiving 
 or 
 dosing of rozanolixizumab at the time of the event or assessment. Listings will include a 
flag indicating whether the the participant was receiving
 or 
 dosing of 
rozanolixizumab at the time of the event or assessment. Because some participants switched 
from 
 to 
 dosing, the N for all participants may differ from the sum of the Ns for 
 and 
 participants. 
For results disclosure on public registries (eg. ClinicalTrials.gov), treatment-emergent adverse 
events and treatment-emergent serious adverse events will be published. 
8.1 
Statistical analysis of the primary safety endpoints 
8.1.1 
Estimand Details and Attributes to be considered for the evaluation of the 
primary endpoints 
The following estimand attributes will be used for all participants: 
Treatment conditions: Fixed dose equivalent to 
 and approximately 
 either 
 or 
. Analyses will be split based on dosing regimen at the time 
of the event. 
1. 
Population: Adult Study Participants with Primary Immune Thrombocytopenia (ITP) 
who fulfill the inclusion / exclusion criteria according to the protocol  
2. 
Endpoints:  See Sections 8.2 for more details. 
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3. 
Intercurrent Events: See below. 
Table 8-1: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of the primary endpoint 
Intercurrent Events (ICE) 
ICE Strategy 
Missing Data Strategy 
a) Use of Rescue therapy from 
Baseline prior Week 54  
Treatment Policy. All data 
will be reported as obseved 
regardless of intercurrent 
event. 
All data available will be 
reported. Missing values will not 
be imputed or included in the 
analysis. 
b) Withdrawal from study due 
to TEAEs 
c) COVID-19* 
*COVID-19 Impact category: Temporary discontinuation of study drug, Permanent discontinuation of study drug, 
Termination of study participation and Relationship to COVID-19: confirmed, suspected, general or other as 
recorded in the COVID-19 impact eCRF form. 
4. 
Population Summary: All primary safety analyses will be based on the SS and will be 
summarized using descriptive statistics. Further details for adverse event summaries, 
laboratory evaluations, ECGs, and vital signs are elaborated in the sections below. 
8.2 
Adverse events 
8.2.1 
Data considerations 
Adverse events will be recorded from the time of informed consent until study completion. All 
AEs will be coded (Section 3.7). 
In addition, AEs will be classified according to the Common Terminology Criteria for Adverse 
Events (CTCAE) Version 5 or later for severity. For any AEs where it is not possible to provide 
a CTCAE grading, the events will be assessed using a standard severity classification (mild, 
moderate, and severe). For the purpose of the tabulations, all CTCAE toxicity classifications will 
be mapped to a mild/moderate/severe grade as described below:  
CTCAE Toxicity Grade: Severity  
− Grade 1: Mild 
− Grade 2: Moderate 
− Grade 3, 4, 5: Severe 
− Not gradable 
In summaries including intensity, the categories will be summarized according to the following: 
Grade: Intensity  
− Grade 1: Mild 
− Grade 2: Moderate 
− Grade 3: Severe 
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For AEs that were not classified according to the CTCAE Toxicity (Severity) criteria, the 
standard intensity Grade will be applied. In case there are mismatches between Severity and 
Intensity Grade, the worst case (i.e., the most severe grade) will be applied.  
Treatment-emergent AEs are defined as AEs starting after the time of first IMP administration up 
to and including 8 weeks (56 days) after the final dose. 
AEs before first dosing and AEs after 8 weeks (56 days) following the final dose will be 
combined in one category and listed. 
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent 
unless evidence exists that does not allow the AE to be treatment-emergent. Handling of missing 
dates for classification of AEs as TEAEs is described in Section 4.1.4 . 
A Persistent AE is defined as an unresolved AE that extends continuously from 
TP0003/TP0006 and does not worsen in intensity or severity following exposure to IMP in 
TP0004. Persistent AEs will be recorded in the TP0004 database. If the intensity or severity of a 
persistent AE worsens it will be considered a new event and reported using the rules detailed 
below. The following rules will be used to assign a TEAE to a study period:  
TEAE-Treatment Period: a TEAE will be assigned to the Treatment Period  for the tabulations 
if the start date of the event is on or after the date of the first administration of IMP up to 
 
following the final dose of IMP within the treatment period.  
TEAE-Safety Follow-Up Period: a TEAE will be assigned to the Safety Follow-Up Period for 
the tabulations if the start date of the event is greater than 
 after the date of the final dose 
of IMP 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 an AE leading to early withdrawal in the Treatment Period, a TEAE will be 
assigned to the Treatment Period based on the last received infusion plus 
 Subsequent 
TEAEs (up to 8 weeks post-last dose) will be assigned to the Safety Follow-Up Period. 
AEs will be presented as “number of participants (percentage of participants) [number of 
events]”.  In this style of output, “[number of events]” will include all cases of an AE including 
repeat occurrences in individual participants, while “number of participants” will count each 
participant only once.  
AE analysis will also be presented by the dosing regimen received at the start of the adverse 
event (either 
 or 
 dosing). 
8.2.2 
Adverse Event Summaries  
The number and percentage of participants who experience AEs will be summarized separately 
by dosing regimen using the SS.  
The following outputs will be created: 
1. Incidence of TEAEs (defined as the number and percentage of participants with at least 
one TEAE (incidence proportion) – Overview. The following categories will be included 
by dosing regimen (
 or 
):  
- 
Any TEAEs 
- 
AESMs 
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- 
AESIs 
- 
Serious TEAEs 
- 
TEAEs leading to Study Discontinuation 
- 
Permanent Withdrawal from IMP due to TEAEs 
- 
Treatment-related TEAEs 
- 
TEAEs with CTCAE Grade 3 and above [or rated as ‘severe’ for events with no 
CTCAE classification] 
- 
All Deaths (AEs leading to death) 
- 
All Deaths (TEAEs leading to death) 
- 
TEAEs leading to dose modification (defined as TEAEs with an action taken with 
study medication of "dose increased" or "dose decreased"). This excludes withdrawal 
of IMP  
- 
TEAEs resulting in temporary treatment interruption 
 
The following summaries will be created by SOC, HLT and PT by dosing regimen (
/
 using the SS, unless stated otherwise: 
 
2. 
Incidence of fatal TEAEs by relationship  
3. 
Incidence of Serious TEAEs by Relationship  
4. 
Incidence of TEAEs leading to Permanent discontinuation of IMP 
5. 
Incidence of Non-serious TEAEs Above Reporting Threshold of 5% of participants by 
System Organ Class and Preferred Term 
− AESIs are 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. 
− AESMs are severe headache, severe GI disturbance (i.e., diarrhea, abdominal pain, 
vomiting), opportunistic infections, arterial and venous thrombotic and thromboembolic 
events. 
− AESMs and AESIs will be identified based on the assessment by the Investigator as 
recorded in the CRF. An AE will be counted as an AESM if there is a ‘yes’ response to 
the question “Is this an event of Special Monitoring?” and ‘no’ otherwise. An AE will 
be counted as an AESI if there is a ‘yes’ response to the question “Adverse Event of 
Special Interest?” and ‘no’ otherwise. 
 
Listings will be presented by dosing regimen, most recent dose, and participant 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, most recent dose, 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), AESMs, and AESIs. Most 
recent dose and dosing regimen will also be included. 
AEs of Focus: 
AEs of Focus will be defined using Version 3.0 or later of “Adverse Events of Focus for the 
Rozanolixizumab program”. In addition, worsening thrombocytopenia and 
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haemorrhagic events will be included as AEOF as described in AEOF Version 1.4. The 
following AEs are defined in the Rozanolixizumab program as AEs of Focus (please see 
Appendix 13.1 for more details)  
− Headaches 
− Gastrointestinal Disturbances 
− Hypersensitivity Reactions 
− Anaphylactic Reactions 
− Injection Site Reactions 
− Infusion Reactions 
− Opportunistic Infections 
− Reductions in Albumin and Plasma Proteins 
− Effects on the Kidney 
− Drug Related Hepatic Disorders 
− Thromboembolic Events 
− Hemorrhagic Events 
− Worsening of Thrombocytopenia 
AEOFs will be listed only.  
8.3 
Vital Signs, Physical Findings, and Other Observations Related to 
Safety 
8.3.1 
Vital Signs and Physical Findings 
The following vital signs measurements will be obtained: 
− Pulse rate 
− Systolic and diastolic blood pressure 
− Temperature (oral, tympanic, or axillary) 
A summary of participants who met each of the Marked Abnormality (MA) Criteria (Appendix 
13.3 ) will be summarized separately by dosing regimen at each scheduled timepoint using the 
SS.  
A by-participant listing of all vital sign measurements (defined in Section 3.3 ) will be presented 
for SS by timepoint. The listing will include a flag for values identified as MA criteria 
(Appendix 13.3). Dosing regimen will be included in the listing. 
Repeated and unscheduled measurements will be handled as described in Section 4.2. 
8.4 
12-lead Electrocardiograms (ECG) 
12-Lead ECG data (measured values and changes from Baseline as defined in Section 3.3) will 
be listed only.  
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The following variables will be reported: 
− Heart rate 
− PR interval 
− RR 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) 
• A summary of participants who meet each of the Marked Abnormally (MA) criteria outlined 
in Appendix 13.4 will be summarized on the SS at each timepoint. Visits where triplicate 
ECGs were performed will be designated by a “*”. 
8.5 
Clinical Safety Laboratory Assessments  
Laboratory data (as specified in Table 10-1: Protocol-required safety laboratory assessments in 
the protocol) and changes from Baseline (if applicable) for numeric variables will be listed 
separately by participant and timepoint using the SS. Baseline will be the pre-dose value 
obtained at the Visit 1 (Week 1 Day 1) result. 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 Laboratory assessments – MA 
Criteria (Appendix 13.2 ). 
Measurements BLQ will be imputed with half of the LLOQ for the purpose of calculating 
change from Baseline. Measurements ALQ, if applicable, will be imputed to the upper 
quantification limit. These rules will be applied to all safety laboratory data including clinical 
chemistry and urinalysis. 
Descriptive statistics will be calculated if at most 1/3 of the individual data points at a time point 
are missing or are either not quantifiable (<LLOQ) or ALQ. Values that are BLQ will be 
replaced by the numerical value of the LLOQ/2 in this instance and values that are ALQ will be 
imputed to the value of the upper quantification limit. If more than one-third of the individual 
data points at a timepoint are missing or not quantifiable (BLQ and/or ALQ), no descriptive 
statistics will be calculated. 
The following summaries/tables will be created: 
− A summary of all participants who met each of the Laboratory assessments – MA 
criteria (Appendix 13.2 ) will be summarized by dosing regimen (using SS) at each 
timepoint. 
A listing for laboratory assessments will be also created using the SS. The listing will include 
dosing regimen. 
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8.5.1 
Potential Drug-Induced Liver Injury 
Data from subjects with any of the laboratory results meeting the criteria for potential drug-
induced liver injury (PDILI) (below) will be listed separately by participant and visit using the 
SS to include: 
− Subjects with at least one post-Baseline liver laboratory assessment 
− Incidence of potential hepatotoxicity with symptoms potentially associated with 
hepatitis or hypersensitivity, which will account for the number and percentage of 
subjects meeting laboratory criteria for pDILI for at least 1 visit and reporting at least 1 
symptom potentially associated with hepatitis or hypersensitivity according to the 
Investigator on the pDILI CRF) 
− Incidence of potential hepatotoxicity with no symptoms potentially associated with 
hepatitis or hypersensitivity, which will account for the number and percentage of 
subjects meeting laboratory criteria for pDILI for at least 1 visit and not reporting any 
symptom potentially related to hepatitis or hypersensitivity according to the 
Investigator on the pDILI CRF 
− Number and percentage of study participants who meet the Laboratory criteria for 
pDILI (see Table 8-2 below).  
Table 8-2: Laboratory criteria for pDILI  
Laboratory Criteria 
Comments 
(AST or ALT > 3 x ULN) and TBL > 1.5 x ULN 
- All values must be met at the same sample 
taken from the same visit 
(AST or ALT > 3 x ULN) and TBL > 2 x ULN 
(AST or ALT > 3 x ULN) and TBL > 2 x ULN 
and ALP < 2 x ULN  
- All values must be met at the same visit 
- To be counted as potential Hy’s Law, all 
criteria must be met at the same sample 
taken from the same visit. 
ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; TBL = total bilirubin; ULN = upper limit of 
normal range. 
A listing will be created of only visits for which at least one of the above criteria was fulfilled for 
a given participant and will display all results obtained at that visit for the specified parameters. 
The listing will specify AST, ALT, TBL, and ALP. 
8.6 
Extent of exposure 
The following summary will be created overall and for each dosing regimen using the SS 
separately: 
a) Study IMP duration and Subject-Years of Time at Risk using descriptive statistics, the 
total of IMP duration (subject-years, which is a subset of total time at risk excluding non-
treated periods) and total time at risk (subject-years). In all calculations, if the participant 
dies and the date of death is missing, the date of death can be imputed as the date of last 
infusion of the treatment the participant was taking. 
• The number of days on IMP (extent of exposure), will be summarized using 
descriptive statistics for the overall treatment period.   
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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 
The number of days on 
 dosing will be calculated as follows:   
Number of days on IMP = [(Date of Last 
 Dose Received) - 
(Date of First 
 Dose Received)] + 1 
The number of days on 
 dosing will be calculated as follows:   
Number of days on IMP = [(Date of Last 
 Dose Received) - 
(Date of First 
 Dose Received)] + 1 
In all calculations, if a patient dies and the date of death is missing, the date of 
death can be imputed as the date of last infusion of the treatment the participant 
was taking. 
• Subject-Years of Time at Risk:  
• For study participants who complete the study as planned and continue into 
the MAP (Managed Access Program), and therefore do not have the SFU visit 
in the parent study 
Date of last visit – Date of first dose + 1 
• For study participants who die prior to the final visit 
Date of death – Date of first dose + 1 
• For all other study participants, use the minimum of the following: 
Date of last dose – Date of first dose + 56 
Or 
Date of last clinical contact – Date of first dose + 1 
• This last group could include study participants who discontinue early or 
study participants who are ongoing in the SFU period at the time of the data 
snapshot.  
• Subject-Years of Time at Risk for 
 Dosing 
• For study participants who do not switch to 
 dosing, time at risk for 
 dosing is the same as total time at risk 
• For study participants who switch to 
 dosing, time at risk for 
 
dosing is  
Date of First 
 Dose Received - Date of First 
 Dose 
Received + 1 
• Subject-Years of Time at Risk for 
 Dosing 
• For study participants who do not switch to 
 dosing, time at risk for 
 dosing is zero days 
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• For study participants who complete the study as planned and continue into 
the MAP, and therefore do not have the SFU visit in the parent study 
Date of last visit – Date of first 
 dose + 1 
• For study participants who die prior to the final visit 
Date of death – Date of first 
 dose + 1 
• For all other study participants, use the minimum of the following: 
Date of last dose – Date of first 
 dose + 56 
Or 
Date of last clinical contact – Date of first 
 dose + 1 
• This last group could include study participants who discontinue early or 
study participants who are ongoing in the SFU period at the time of the data 
snapshot.  
 
• The total time at risk is calculated as the sum of the person-time at risk (days) 
across all participants in the population divided by 365.25. 
As described in the protocol, fixed-unit doses across body weight tiers and dosing 
regimen will be employed in this study according to the following scheme, as presented 
in Table 8-3. 
Table 8-3: TP0004 dose levels and weight tiers of rozanolixizumab  
Dose eqv 
 
Bodyweight 
 
Dose level 1 
 
Dose level 2 
 
 Dose level 3 
>35 to <50kg 
 
 
No weight adjustment    
 
≥50 to <70kg 
 
 
≥70 to <100kg 
 
 
≥100kg 
 
 
eqv=equivalent 
If a study participant is in the lowest body weight tier (below 50kg) and is on the lowest dose 
level with a platelet count between >150×109/L and <400×109/L, the investigator might decide to 
temporarily stop treatment according to medical judgement based on the observation of platelet 
variability. If the platelet count increases above 400×109/L then treatment must be stopped 
anyway. 
A listing with all drug administration details including date, start and stop time of infusion, 
interruptions, discontinuations, dose, volume delivered, percent of planned dose and reasons for 
any interruptions or discontinuations will be created using the SS.  
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8.7 
Concentrations of Total Protein & Albumin  
Concentrations of total protein and albumin for each visit (as described in the schedule of events 
in the protocol) will be listed using the SS. 
8.8 
 Serum and Plasma Complement Levels 
Serum (C3 and C4) and plasma (C3a and C5a) complement variables will be listed by time point.  
Measurements below the limit of quantification (BLQ) will be imputed with half of the lower 
limit of quantification (LLOQ). Measurements above the limit of quantification (ALQ), if 
applicable, will be imputed to the upper limit of quantification. 
All analyses described in this section will be performed on the SS. 
8.9 
Other Safety Variables 
8.9.1 
Physical examination 
Results of physical examination abnormalities will be listed. 
8.9.2 
Pregnancy testing 
The pregnancy test will be a urine pregnancy test at all visits as per schedule of assessments. If 
the urine pregnancy test is positive, then a confirmatory serum pregnancy test is required. 
A by-participant listing of the pregnancy test data will be provided for the SS. 
8.9.3 
Childbearing potential 
Childbearing potential will be collected at Baseline. A by participant listing will be provided for 
all the participants enrolled. 
8.9.4 
Assessment and management of Tuberculosis 
Results of the interferon-gamma release assay tuberculosis (TB) test will be listed. 
Results of the chest X-ray for TB will be listed. 
Results of TB signs and symptoms questionnaire will be listed.  
8.9.5 
COVID-19 Impact 
A listing of impact of COVID-19 pandemic for any reason (including impact category and visit 
(timepoint)) by dosing regimen using the ES will be created. 
9 
EFFICACY ANALYSES 
Data will be listed, and for continuous variables, descriptive statistics will be generated for the 
observed values and changes from Baseline. For categorical variables, frequency counts and 
percentages will be presented.   
All summary outputs for the secondary efficacy endpoints will be presented by visit, and by the 
treatment received in the parent studies (TP0003/TP0006) . 
The following estimand attributes will be used for all participants 
1. Treatment conditions: Fixed dose equivalent to 
 and approximately 
 either 
 or 
 based on body weight tiers.  
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2. Population of Interest: Adult Study Participants with Primary Immune 
Thrombocytopenia (ITP) who fulfill the inclusion / exclusion criteria according to the 
protocol  
The remaining Estimand Attributes are presented below for each efficacy endpoint. 
9.1 
Statistical analysis of the secondary efficacy endpoints 
9.1.1 
Stable Clinically Meaningful Response 
The secondary efficacy endpoint will be analyzed according to the following Estimand 
Attributes: 
3. Endpoint:  Stable Clinically Meaningful Response, defined as Clinically Meaningful 
Response (ie, platelet count ≥50×109/L) without rescue therapy at ≥70% of the visits 
over the planned 52 week Treatment Period starting at Week 4  
4. Intercurrent Events: see below. 
Table 9-1: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of the secondary efficacy endpoint 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Use of Rescue therapy from 
Baseline prior Week 54 
A composite strategy   
Participants impacted by any 
ICE (a, b, c and d) will be 
considered as non-responders 
starting from the time of event. 
 
 
Not applicable 
b) Participants who experience any 
TEAEs leading to permanent 
treatment discontinuation 
c) Participants who discontinue 
prior to receiving IMP  
d) Participants who do not have 
any post-treatment assessment 
e) COVID-19* 
A composite strategy   
Participants impacted by ICE (e) 
will be considered as non-
responders at the time of event. 
* COVID-19 Impact category: Temporary discontinuation of study drug, Permanent discontinuation of study drug, 
Termination of study participation and Relationship to COVID-19: confirmed, suspected, general or other as 
recorded in the COVID-19 impact eCRF form. 
5. Population-level summary: Owing to early termination of the study, the population-
level summary will be provided using descriptive statistics. 
The following efficacy endpoints will be analyzed using the SS and will follow the same 
considerations for treatment condition and population of interest from Section 9.1 above. 
9.1.2 
Change from Baseline to Week 53 or 55 for ITP-PAQ Symptoms domain 
score 
3. Change in ITP-Patient Assessment Questionnaire (ITP-PAQ, see section 8.1.3.1 in the 
protocol for details) Symptom score will be calculated at week 53 or 55 relative to the 
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Baseline and will be limited to the participants with a Baseline ITP-PAQ score available. 
Please see Section 13.5 for details about ITP-PAQ scoring and ITP-PAQ scales. 
Summary will be by dosing regimen. Week 53 will be used for participants who finished 
the study on 
 dosing, and week 55 will be used for participants who finished the 
study on 
 dosing. The intercurrent event strategy is as follows: 
4. Intercurrent Events: see below. 
Table 9-2: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of Change from Baseline to Week 53 or 55 for 
ITP-PAQ Symptoms domain score 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Use of Rescue therapy from 
Baseline prior Week 53 or 55 
A composite strategy   
Participants impacted by any 
ICE (a, b, c and d) will be 
considered as non-responders 
starting from the time of event 
and change from baseline to 
week 53 or 55 will be set to 0. 
 
 
In case of missing ITP-
PAQ assessment at 
Baseline or week 53 or 
55, this endpoint will 
be set to blank  
b) Participants who experience any 
TEAEs leading to permanent 
treatment discontinuation 
c) Participants who discontinue 
prior to receiving IMP  
d) Participants who do not have 
any post-treatment assessment 
e) COVID-19* 
 
A composite strategy   
Participants impacted by ICE 
(e) will be considered as non-
responders at the time of event. 
If ICE occurs at week 53 or 55, 
change from baseline to week 
53 or 55 will be set to 0. 
5. Population-level summary: Owing to early termination of the study, the population-
level summary will be provided using descriptive statistics. 
9.2 
Statistical analysis of the other efficacy endpoints 
9.2.1 
Mean Change from Baseline in platelet count at each visit 
Mean Change from Baseline (as collected on TP0004 Visit 1/BL) in platelet count at each visit 
will be summarized separately on the SS using descriptive statistics at each timepoint. 
Summaries will be presented by treatment received during the parent study (TP0003/TP0006), 
either rozanolixizumab or placebo. Summary will be by dosing regimen. The ICE strategy will 
be as follows: 
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Table 9-3: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of Mean Change from Baseline in platelet 
count at each visit 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Use of Rescue therapy from 
Baseline prior Week 53 or 55  
A while-on-treatment strategy   
Participants impacted by the 
ICE (a) will be excluded from 
summaries and change in 
baseline starting from the time 
of the event. 
 
 
Not applicable 
9.2.2 
Clinically Meaningful Response at each visit 
Clinically meaningful response at each visit will be summarized on the SS at each timepoint. 
Summaries will be presented by treatment received during the parent study (TP0003/TP0006), 
either rozanolixizumab or placebo. Summary will be by dosing regimen. The ICE strategy will 
be as follows: 
Table 9-4: Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and Missing 
data Strategies for the analysis of Clinically Meaningful Response at each 
visit 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
b) Use of Rescue therapy from 
Baseline prior Week 53 or 55  
A while-on-treatment strategy   
Participants impacted by the 
ICE (a) will be excluded from 
summaries and change in 
baseline starting from the time 
of the event. 
 
 
Not applicable 
9.2.3 
ITP-BAT bleeding events and severity by visit 
ITP-BAT bleeding events and severity by visit, will be listed on the SS. Dosing regimen will be 
included in the listing. 
Table 9-5: ITP-specific Bleeding Assessment Tool (ITP-BAT) Domains and categories 
Skin 
Mucosal 
Organ 
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- Petechiae 
- Ecchymoses 
- Subcutaneous 
Hematomas 
- Bleeding from Minor 
Wounds 
- Epistaxis 
- Oral cavity [a] 
- Subconjunctival 
Hemorrhage 
- Gastrointestinal Bleeding Not 
Explained by Visible Mucosal Bleeding 
or Lesion 
- Lung Bleeding 
- Hematuria 
- Menorrhagia 
- Intramuscular Hematomas 
- Hemarthrosis 
- Ocular Bleeding 
- Intracranial Bleeding 
- Other Internal Bleedings 
[a] Includes gum bleeding, hemorrhagic bullae or blisters, bleeding after bites to lip & tongue or after deciduous 
teeth loss 
Notes:  
− Presence of bleeding will be indicated by a Mucosae or Organs Grade ≥1, or Skin Grade 
≥2.  
− Bleeding reported by the participant without medical documentation will be graded 1. 
− Fatal bleeding will be graded 5. 
− Within each domain, the same grade is assigned to bleeding manifestations of similar 
clinical impact.  
− The “worst” bleeding manifestation since the last visit will be graded, and the highest 
grade within each domain will be recorded. 
Please see Section 13.6  ITP bleeding score for more details. 
10 
PHARMACOKINETICS (PK) AND PHARMACODYNAMICS 
(PD) 
10.1 
Pharmacokinetic endpoints 
10.1.1 
Plasma Concentration of Rozanolixizumab  
Individual plasma concentration of Rozanolixizumab will be summarized by scheduled sampling 
day for the PK-PPS using n, arithmetic mean, median, SD, minimum, maximum, geometric 
mean (geomean), geometric coefficient of variation (geoCV) and 95% CI (assuming log-
normally distributed data) overall. The following sample exclusions will be applied in the 
summary: 
1. If dose is missed – the next predose PK sample 2 weeks after would be impacted and is 
excluded.  
2. If dose is given >=3 days out of allowed window (that would be 5 days out in total as 
visit window is typically ±2 days) after what it should be given – the current predose PK 
sample if it is also delayed and the next predose sample if taken at the per protocol 
planned time and it is not readjusted based on dosing, could be impacted and thus we 
would exclude it. 
3. If dose is given >=3 days out of window (that would be 5 days out in total) before what it 
should be given – the PK predose sample of the impacted dosing visit and the next 
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predose PK sample if taken at the per protocol planned time and it is not readjusted based 
on dosing, could be impacted and thus we would exclude it. 
4. If dose is given at the right time but next PK visit is impacted by >=3 days out of the 
window, then the next PK visit is the one impacted and excluded 
5. For weeks 13 and 23 if a postdose PK sample 1 to 5 days is taken, if the postdose sample 
is not taken within 1 to 5 days post actual dose, then it would need to be excluded. 
6. For PK samples on Day 3, Day 5, and Day8, if outside window then exclude from table. 
The following rules will apply for PK data listings and summaries: 
• Values below the LLOQ will be reported as below the limit of quantification (BLQ) 
• Descriptive statistics of concentrations will be calculated if at most 1/3 of the individual data 
points at a timepoint are missing or are not quantifiable (<LLOQ). Values that are BLQ will 
be replaced by the numerical value of the LLOQ/2 in this instance.  
• The 95% CI lower and 95% CI upper should be left blank if the SD (or equivalently, the 
geoCV) is 0 
• The geoCV will be calculated using the following formula where SD is the standard 
deviation from the log-transformed data 
geoCV (%) = sqrt[(exp (SD^2) – 1)] x 100   
Individual concentrations of rozanolixizumab will be listed for the RS for each individual with 
the actual time and will include the equivalent dose and actual dose being administered previous 
to the pk sample, the sampling time in days relative to the previous dose, the IgG observed at the 
same visit, the ADA titer observed for the binding assay and the NAb titer for the same visit and 
platelet count for the corresponding visit.   
10.2 
Antidrug Antibodies (ADA) 
The immunogenicity analysis will be done on the SS.  
Anti-rozanolixizumab antibodies will be measured using a three-tiered assay approach: screening 
assay, confirmatory assay and titration assay. Samples will first be evaluated in the screening 
assay (reported as ‘negative screen’ or ‘positive screen’), followed by analysis of screened 
positive samples in the confirmatory assay to confirm the true positivity of the samples (reported 
as ‘negative immuno-depletion’ or ‘positive immuno-depletion’). Samples that are confirmed as 
positive in the confirmatory assay will be evaluated in a titration assay to quantify the ADA level 
and will be reported as titer (reciprocal dilution factor including minimum required dilution 
(MRD)). Any sample confirmed positive for ADA within the confirmatory assay will be further 
evaluated for the presence of neutralizing anti-rozanolixizumab antibodies.  
Screening, confirmatory, and titer cut points of the respective assays will be determined by the 
bioanalytical laboratory. The relevant statistical reports will be provided as part of the 
bioanalytical reports. Rozanolixizumab has the potential to interfere with the antibody assay at 
concentrations above the drug tolerance limit (DTL); therefore, an integrated evaluation of anti-
rozanolixizumab antibody results and rozanolixizumab plasma concentration will be used to 
enable the interpretation of immunogenicity results. The ADA sample status will be determined 
for each visit where samples were taken for ADA analysis:  
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• Sample values that are either ‘negative screen’ or the combination of ‘positive screen’ and 
‘negative immunodepletion’, will be defined as ADA negative if corresponding 
rozanolixizumab concentrations are equal or below the validated drug tolerance limit of the 
ADA assay 
rozanolixizumab) allowing detection of 100ng/mL ADA 
• Sample values that are either ‘negative screen’ or the combination of ‘positive screen’ and 
‘negative immuno-depletion’, but with corresponding rozanolixizumab concentrations above 
the validated drug tolerance limit of the ADA assay, will be defined as ADA inconclusive  
• Sample values that are ‘positive screen’ and ‘positive immunodepletion’ will be defined as 
ADA positive 
• Samples that could not be tested for ADA status due to inadequate sample volume, 
mishandling, or errors in sample collection, processing, storage, etc., will be defined as 
Missing  
• Neutralizing antibody (NAb) sample status (positive/negative/missing) will be determined 
for ADA positive samples. Samples that are NAb positive will be evaluated in a titration 
assay to quantify the NAb level and will be reported as titer. 
The ADA participant status will be classified on individual and group level as outlined below 
(Shankar et al. 2014; Rup et al, 2015). Individual study participants will be assessed for ADA 
participant status, composed of 6 categories: ADA negative, inconclusive, and ADA positive, 
whereby a positive participant’s status is determined as originating from a treatment-induced, 
boosted, reduced or unaffected ADA response. 
Study participants who are identified as being treatment-induced or treatment-boosted ADA-
positive will be grouped as treatment emergent (TE)-ADA positive participants. Study 
participants who are identified as being treatment-reduced or treatment-unaffected ADA-positive 
will be grouped as non-TE-ADA positive participants. Both TE-ADA positive and non-TE–ADA 
positive participants will be further classified as NAb negative or NAb positive. 
The individual and combined ADA participant categories will be summarized overall through the 
SFU sample if applicable (timepoint of interest). The ADA categories are defined in Table 10-1. 
Notes: 
− The ADA sample status should be determined for each visit where samples were taken 
for ADA analysis. 
ADA Baseline 
By default, the Day 1 of the parent study will be the Baseline value if the ADA status at 
screening (from parent study) is ADA negative or missing. If the ADA status at screening of the 
parent study is ADA positive and ADA status at Day 1 of parent study is ADA negative or 
missing, the screening will be the Baseline value. If the ADA status at screening and Day 1 (of 
the parent study) are same, Day 1 will be the Baseline value.  For participants stratified to 
placebo in the parent study the Baseline value from TP0004 will be used. 
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Table 10-1: Terms and Definitions for ADA Status Evaluation in Study Participants 
Term 
Definition 
Category 
Individual participant categories 
Pre-ADA negative – treatment induced 
ADA negative (ADA-NEG) 
Study participants who have an ADA negative sample 
at Baseline and at all sampling points post-Baseline up 
to the timepoint of interest.  
1 
Inconclusive 
Study participants who have an ADA positive or 
negative Baseline sample and some post-Baseline 
samples are missing or inconclusive, while other post-
Baseline samples are ADA negative up to the 
timepoint of interest.  
2 
Pre-ADA negative – treatment induced 
ADA positive (TI-POS) 
Study participants who have an ADA negative sample 
at Baseline and at least one ADA positive sample at 
any sampling point post-Baseline up to the timepoint 
of interest  
3 
Pre-ADA positive – treatment boosted 
ADA positive (TB-POS) 
Study participants who have an ADA positive sample 
at Baseline and at least one ADA positive sample at 
any sampling point post-Baseline up to the timepoint 
of interest, with increased titer values compared to 
Baseline (greater than a predefined fold difference 
increase from Baseline value which will be defined 
within the validation of the assay ie MSR of the 
assay1)  
4 
Pre-ADA positive – treatment reduced 
ADA positive (TR-POS) 
Study participants with an ADA positive sample at 
Baseline, and ADA negative samples at all sampling 
points post-Baseline up to the timepoint of interest  
5 
Pre-ADA positive – treatment unaffected 
ADA positive (TU-POS) 
Study participants with an ADA positive sample at 
Baseline and an ADA positive sample at any sampling 
point post-Baseline up to the timepoint of interest, 
with titer values of the same magnitude as Baseline 
(less than a predefined fold difference from the 
Baseline value which will be defined within the 
validation of the assay, ie MSR of the assay1) 
6 
Combined participant categories 
Treatment emergent ADA positive (TE-
POS) 
Includes study participants who are treatment induced 
ADA positive (category 3) or treatment boosted ADA 
positive (category 4). 
7 
Non-treatment emergent ADA positive 
(Non-TE-POS) 
Includes study participants who are treatment reduced 
ADA positive (category 5) or treatment unaffected 
ADA positive (category 6). 
8 
Treatment emergent ADA positive – 
NAb positive (TE-POS, NAb-POS) 
Includes study participants who are treatment 
emergent positive (category 7) and have at least one 
NAb positive sample 
9 
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Table 10-1: Terms and Definitions for ADA Status Evaluation in Study Participants 
Term 
Definition 
Category 
Treatment emergent ADA positive – 
NAb negative (TE-POS, NAb-NEG) 
Includes study participants who are treatment 
emergent positive (category 7) and have no NAb 
positive samples 
10 
Non-treatment emergent ADA positive - 
NAb positive (Non-TE-POS, NAb-POS) 
Includes study participants who are non-treatment 
emergent positive (category 8) and have at least one 
NAb positive sample 
11 
Non-treatment emergent ADA positive - 
NAb negative (Non-TE-POS, NAb-
NEG) 
Includes study participants who are non-treatment 
emergent positive (category 8) and have no NAb 
positive samples 
12 
1 The fold difference increase from baseline value, ie, the minimum significant ratio (MSR) determined during assay 
validation, will be reported in the relevant tables, listings and figures. It reflects the fold difference in titer level that 
considered higher than the assay variation in titer determination. The MSR is equal to 1.86. 
The following outputs will be created: 
Summaries by dosing regimen, using SS: 
Tables: 
• Number and percentage of participants with positive, negative, inconclusive, or missing  
sample ADA status at the time of each visit and will be summarized overall. Denominator is 
the number of study participants having a non-missing result at that visit. Summary will be 
by dosing regimen. 
• Number and percentage of participants in each of the ADA participant individual categories 
(1 to 6) and combined (7-12) presented above will be summarized overall. Denominator will 
be the total number of study participants having an individual ADA participant category 
defined 
• Summary tables displaying the total prevalence of pre-existing ADA and NAb, and persistent 
ADA positivity, as defined below: 
- 
Total prevalence of pre-existing ADA and NAb: number and percentage of participants 
having an ADA positive sample status at baseline of the parent study, with the 
denominator being the total number of study participants having a non-missing sample 
result at baseline, by treatment group in the parent study and overall. The same will be 
repeated for NAb. 
- 
Persistent ADA positivity: Number and percentage of study participants with treatment-
induced ADA positive samples detected at 2 or more sequential sampling time points 
during the treatment (including observation and off-treatment periods), where the first 
and last ADA positive samples are separated by at least 16 weeks (equal to 5 half-lives of 
human IgG [22 days], as per Rup et al., 2015), by treatment group in the parent study and 
overall. 
Listings: 
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Listings by timepoint by dosing regimen using the SS will be created. The following datapoints 
will be included: 
- 
Rozanolixizumab concentration 
- 
Total IgG, and absolute platelet counts  
- 
ADA screening results (with the confirmatory result, the ADA titer result if applicable 
and the ADA sample status)  
- 
NAb result titer (when performed) 
- 
Time since administration of IMP (in days) 
- 
Individual ADA participant classification that apply (as defined above) 
- 
Previous visit actual dose (mg/kg equivalent) and actual dose (mg)  
- 
By-subject listing of all TEAEs, including the time of onset, the ADA and NAb sample 
status and ADA and NAb titers at the closest sampling time point prior to and subsequent 
to the TEAE, and time since last administration of IMP (in days). 
10.3 
Pharmacodynamic endpoints 
The following pharmacodynamic endpoints will be summarized separately on the SS.  
10.3.1 
Change from Baseline in Total Serum IgG concentration over time 
Total serum IgG concentrations will be summarized and listed on the SS by time point for 
absolute values, change from Baseline, and percentage change from Baseline. Dosing regimen 
will be included in the listing. 
10.3.2 
Change from Baseline in IgG subclasses concentration over time  
IgG subclasses will be listed on the SS by time point for absolute values, change from Baseline, 
and percentage change from Baseline overall and stratified by body weight tier. Stratification by 
region may be also performed. Dosing regimen will be included in the listing. 
10.3.3 
Serum IG concentrations (IgA, IgE, IgM) over time  
Immunoglobulins (IgE, IgA and IgM) will no longer be summarized; IgE, IgA and IgM 
concentrations will be listed only. Dosing regimen will be included in the listing. 
10.4 
Influence of Rozanolixizumab on vaccination titers 
10.4.1 
Vaccination titers against Streptococcus pneumoniae, Neisseria meningitidis, 
and Haemophilus influenzae in splenectomized study participants 
Vaccine specific antibodies concentrations will be listed to capture absolute values in vaccination 
titers against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in 
splenectomized study participants by visit using the SS. 
10.5 
Effect of Rozanolixizumab on post-vaccination biomarker(s) in 
study participants who received COVID-19 Vaccine 
For study participants who receive the COVID-19 vaccination, post-vaccination biomarkers will 
be listed (using the SS) for vaccination samples in those study participants that were vaccinated 
by all pertaining visits.    
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11 
OTHER ANALYSES 
11.1 
Statistical analysis of other endpoints 
11.1.1 
Effect of Rozanolixizumab on study participant perceived symptoms 
11.1.1.1 
 ITP-PAQ V1 Domain Score 
The ITP-PAQ V1 consists of 44 items that comprise 10 scales. Each of the 10 scales is scored 0 
to 100, with higher scores indicating better quality of life. Four of the scales measure physical 
health: Symptoms, Bother, Fatigue, and Activity. Two of the scales measure emotional health: 
Fear and Psychological Health. The remaining four scales measure other aspects of QOL: 
Work QOL, Social QOL, Women’s Reproductive QOL, and Overall QOL. 
A by-subject listing of the ITP-PAQ V1 questionnaire, ITP-PAQ V1 item responses will be 
provided for using the SS. The listing will include dosing regimen.  
11.1.2 
Reduction in use of steroids in study participants  
11.1.2.1 
Percent change in oral steroid dose over time  
The oral steroid dose will be listed at each timepoint from Week 1 to Week 53 or 55 as available 
depending under which protocol version the patient completed the study. Only one steroid dose 
should be selected between each dose; the start date should be before the timepoint, and the end 
date should be the same day or later than the timepoint.  
11.1.2.2 
Change in dose and/or frequency of concomitant ITP medications 
Dose of permitted concomitant ITP medications (as defined in Protocol Table 6-2) from Week 1 
to Week 52 will be listed as available. 
11.2 
Statistical analysis of other exploratory endpoints 
All exploratory variables will be listed by visit unless otherwise stated. No inferential 
assessments or confirmatory statistical tests will be performed. Descriptive statistics will be 
generated for the observed values and the change from Baseline for all continuous outcomes. For 
categorical variables, frequency counts and percentages will be presented. Dosing regimen will 
be included in all listings. 
11.2.1 
Effect of Rozanolixizumab on Patient Reported Outcomes (PRO)  
11.2.1.1 
FATIGUE-PRO physical fatigue score  
The Fatigue Patient Reported Outcome (PRO) physical fatigue instrument consists of 9 items. 
The scale is 1 out of the 3 scales composing the broader Fatigue instrument developed by UCB. 
Items are rated within a 7-day recall period on a 5-point Likert frequency scale ranging from 
“none of the time” to “all of the time.” 
A by-subject listing of the FATIGUE-PRO items will be provided using the SS for all 
participants.  
11.2.1.2 
Patient Global Impression of Severity (PGI-S) 
The PGI-S consists of a single-state, self-report measure that rates a study participant's severity 
of specific condition, depicting a study participant's rating of overall symptoms (“none” , “mild”, 
“moderate”, “severe”, or “very severe”). 
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A by-subject listing of PGI-S will be provided using the SS for all participants. Dosing regimen 
will be included in the listing. 
11.2.1.3 
Patient Global Impression of Change (PGI-C) 
The PGI-C is a single-state, self-report measure that reflects a study participant's belief about the 
efficacy of treatment for a specific condition, on a 7-point scale depicting a study participant's 
rating of overall improvement (“very much improved”, or “much improved”, “minimally 
improved” , “no change”,  “minimally worse”, “much worse”, or “very much worse”). Dosing 
regimen will be included in the listing. 
A by-subject listing of PGI-C will be provided using the SS for all participants . Dosing regimen 
will be included in the listing. 
11.2.2 
Effect of Rozanolixizumab on Health-Related Quality of Life (HRQoL) 
11.2.2.1 
European Quality of Life-5 Dimensions, 5 Levels Assessment (EQ-5D-5L)  
As described in section 8.5.3.4 in the protocol, the EQ-5D-5L health questionnaire consists of 2 
pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). 
The descriptive system comprises five dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight 
problems, moderate problems, severe problems, and extreme problems. The patient is asked to 
indicate his/her health state by ticking the box next to the most appropriate statement in each of 
the five dimensions. This decision results in a 1-digit number that expresses the level selected for 
that dimension. The digits for the five dimensions can be combined into a 5-digit number that 
describes the patient’s health state. 
The EQ VAS records the patient’s self-rated health on a vertical visual analogue scale, where the 
endpoints are labelled ‘The best health you can imagine’ and ‘The worst health you can 
imagine’. The VAS can be used as a quantitative measure of health outcome that reflect the 
patient’s own judgement. 
Observed values in the European Quality of Life 5 Dimension 5 Levels (EQ 5D 5L) item 
responses and VAS scores will be listed only.  Dosing regimen will be included in the listing. 
11.2.2.2 
Short form 36-item (SF-36) domain and composite scores  
The SF-36v2, standard recall, measures the following eight health domains as rated by the 
subjects over the past four weeks: Physical Functioning, Role Physical, Bodily Pain, General 
Health, Vitality, Social Functioning, Role Emotional, and Mental Health. The classification of 
the questionnaire items to the health domains is shown in Section 13.7. 
The SF-36 PCS and MCS scores are used to measure the two broad components, or aspects, of 
health-physical and mental. PCS and MCS are based on the aggregate of the eight health 
concepts described above and all of the eight health domain scales are used to score both 
components summary measures. 
One additional item asks responders about health change over the past year. 
The SF-36 will be used using QualityMetric’s Health Outcomes™ Scoring Software. The 
software uses updated 2009 U.S. population norms and applies a Full Missing Score Estimation 
(Full MSE) method as follows: 
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• A health domain score (except the PF domain) will be estimated provided that at least one 
non-missing response is available within that domain 
• For the PF domain item, response theory will be used to develop a model for estimates of the 
missing score 
• Regression methods are then applied to estimate the PCS and the MCS on the basis of the 
available domains. 
A by-subject listing of the SF-36 item responses will be provided using the SS for all participants 
by dosing regimen. Dosing regimen will be included in the listing. 
11.2.3 
Resource Utilization 
A listing for the number and length of hospitalizations will be also produced using the ES by 
dosing regimen. 
The number of Infusion Center Admissions will be summarized and listed in a similar manner. 
11.2.4 
Experience with the Subcutaneous self-administration 
PRE-Self Injection Assessment Questionnaire (SIAQ) (Infusion version) domains scores before 
the first sc self-administration will be listed for participants that self-administer. POST-SIAQ 
(Infusion version) domains scores will also be listed at each available visit in participants by 
dosing regimen that self-administer. The SS will be used. 
11.3 
Specific analyses for Pharmaceuticals and Medical Devices Agency 
(PMDA) 
Separate listings or summaries will not be presented for Japanese participants. 
11.4 
Headache Questionnaire 
The results of the “Symptoms and Frequency of Severe Headache” questionnaire will be listed 
for each participant. No summary tabulations will be provided for these assessments. The SS will 
be used. 
12 
REFERENCES 
Levey et al. A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2009; 
150: 604-612. 
Nehring, S.M.; Goyal, A.; Patel, B.C. (2020). StatPearls Publishing, web link: 
https://www.ncbi.nlm.nih.gov/books/NBK441843/. 
Rup et al (2015). Clin Exp Immunol. 181:385 – 400. 
Shankar et al (2014). AAPS 16:4. DOI:10.1208/s12248-014-9599-2. 
United States Department of Health and Human Services, National Cancer Institute. Common 
Terminology for Adverse Events (CTCAE), Version 5.0, November 17, 2017. 
 
 
 
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13 
APPENDICES 
13.1 
AE of focus for the Rozanolixizumab Program 
The purpose of this appendix is to detail the approach to identifying TEAEs meeting criteria for 
AEs of focus (AEOF) for the rozanolixizumab program.  
Table 13-1: Following Events are Adverse Event of focus For Rozimab for All Indications 
and for ITP-specific Events: 
 
No 
Event (also included in 
Title of TFL output) 
Selection criteria 
1 
Headache 
(Note: also included in 
AESM if severe) 
TEAE with HLGT=’Headaches’ 
2 
Gastrointestinal disturbances 
(Note: also included in 
AESM if severe) 
TEAE with  
HLT=‘Gastrointestinal and abdominal pains (excl oral and 
throat)’ or  
HLT=‘Gastrointestinal signs and symptoms NEC’ or   
HLT=‘Nausea and vomiting symptoms’ or 
HLT=‘Diarrhoea (excl infective)‘ or 
HLT=‘Gastritis (excl infective)’ 
3 
Hypersensitivity reactions  
 
SMQ=’Hypersensitivity’ 
4 
Anaphylactic reactions 
SMQ=‘Anaphylactic reaction’ and  
TEAEs that either emerged on the same day as when a study 
medication injection reaction was received, or that emerged one 
day after a study medication injection was received, and which 
fulfill any of the following 3 criteria should be included in the 
summary table: 
 
1. If a subject reports any TEAE which codes to a PT included 
in Category A, then the event will be flagged as an 
anaphylactic reaction. 
 
2. If a subject reports any TEAE which codes to a PT included 
in Category B AND reports any TEAE which codes to a PT 
included in Category C, and both TEAEs have the same 
start date, then both events will be flagged as anaphylactic 
reactions.  
 
3. If a subject reports any TEAE which codes to a PT included 
in Category D AND reports (either a TEAE which codes to 
a PT included in Category B OR a TEAE which codes to a 
PT included in Category C), and both TEAEs have the 
same start date, then both events will be flagged as 
anaphylactic reactions. 
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5 
Injection site reactions 
TEAE with 
HLT=’Injection site reactions’ or 
HLT=’Infusion site reactions’ or 
HLT=’Administration site reactions NEC’ 
6 
Infusion Reactions  
Infusion reaction marked on AE CRF page 
(based on the assessment by the Investigator) 
7 
Infections 
TEAE with SOC =”Infections and infestations”  
Note: This was added as a reminder for safety that infections 
are considered as AE of focus and require assessment. No 
programming of this topic is required as TEAEs can be found in 
general AE Tables.  
8 
Opportunistic infections 
(Note: also included in 
AESM) 
Opportunistic infections (including tuberculosis) will be 
summarized in a stand-alone table using UCB-defined search 
criteria. Opportunistic infections are identified in two steps 
using the attached spreadsheet 
for MedDRA v24.0: 
OI_MedDRA24_0.xls
x
 
 
Step 1: Refer to column B of the spreadsheet which identifies 
the Preferred Terms (PTs) to be classified as opportunistic 
infections using either a single ‘x’ or a double ‘xx’. 
• TEAEs which code to a PT flagged with a single ‘x’ 
need to also be serious in order to be considered an 
opportunistic infection.  
• All TEAEs which code to a PT flagged with a double 
‘xx’ are considered to be an opportunistic infection, 
regardless of seriousness.  
All serious TEAEs in the study database which code to a PT 
flagged with a single ‘x’ and all TEAEs in the study database 
which code to a PT flagged with a double ‘xx’ will be 
summarized as an opportunistic infection in the stand-alone 
table. [CQ97NAM= ’Opportunistic Infection - Automatic’] 
 
Step 2: Refer to column C of the spreadsheet which identifies 
the PTs that need to be evaluated on a case-by-case basis by the 
study physician and safety physician in order to determine 
whether it is a true opportunistic infection or not. The process 
for physician review is as follows: 
1. Study programming team creates a spreadsheet which 
lists all of the subjects with a TEAE present in the 
database which codes to a PT identified as case-by-case. 
[CQ98NAM= Opportunistic Infection - Manual Review 
Candidate]  
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Information from the AE dataset to be included in the 
spreadsheet: Subject ID, AE verbatim term, System 
Organ Class (SOC), High Level Term (HLT), Lower 
Level Term (LLT), PT, AE start date, AE end date, 
seriousness, severity, relationship to study medication, 
action taken. Additionally, a column will be included 
where the study physician/safety physician can 
document their decision on the case. 
2. Study physician/safety physician (SPs) reviews the cases 
in the spreadsheet separately and reconciles final 
decision, and indicates in the additional column which 
AEs are confirmed to be opportunistic infections via a 
single ‘x’. 
3. Study programming team incorporates these decisions 
into the AE dataset by merging the SPs decisions for 
individual subjects / PTs and flagging both the 
automatic and the confirmed opportunistic infections as 
such in the dataset. 
 [CQ99NAM= ‘Opportunistic Infection – Adjudicated’] 
 
The SPs reviews the context of all of a subject’s data (AEs and 
possibly other) and concludes individually.   
Indicators of relevant cases may be e.g. repetitive occurrences, 
conjunction of other events or findings considered relevant.  
All subjects with a case-by-case PT reported that has been 
confirmed by the SPs to be an OI will be summarized as such in 
the stand-alone table, along with all of the events identified in 
Step 1 of this process.  
[CQ99NAM= ‘Opportunistic Infection – Adjudicated’]  
The timing and frequency of Step 2 should be outlined and 
agreed to by the study team at the beginning of the study. It is 
suggested that this process be executed multiple times 
throughout the course of the study, more frequently in the 
weeks leading up to database lock, and one final time 
immediately prior to database lock.   
 Following the initial physician review of case-by-case events, 
subsequent reviews will be based on the cumulative set of case-
by-case events present in the database at each time point of 
spreadsheet creation.   
  
Physician decisions from previous runs should be retained in 
each subsequent run. The final run of the spreadsheet, with all 
SP decisions on the full set of case-by-case events, will be 
archived at the conclusion of the study analysis prepared for 
agency submission. 
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9 
Reductions in albumin and 
plasma proteins 
TEAEs with 
PT=’Blood albumin decreased’ or 
PT=’Protein albumin ratio’ or 
LLT=’Plasma protein abnormal’ or 
LLT=’Proteins serum plasma low’ 
10 
Effects on the kidney 
TEAEs in  
SMQ= ‘Acute renal failure’ 
11 
Drug related hepatic 
disorders  
TEAEs in  
SMQ=’Drug related hepatic disorders - comprehensive search’ 
12 
Effect on lipids 
TEAEs with  
PT= ‘Blood cholesterol increased’ or  
PT= ‘Low density lipoprotein increased’ or  
PT= ‘Blood triglycerides increased’ or  
PT= ‘Hypercholesterolaemia’ or  
PT= ‘Hypertriglyceridaemia’ or  
PT= ‘Hyperlipidaemia’ or  
PT= ‘Dyslipidaemia’ or  
PT= ‘Lipids increased’ 
13 
Thromboembolic events 
Embolic and thrombotic events (SMQ) 
14 
Worsening 
thrombocytopenia * 
Haematopoietic thrombocytopenia (SMQ) 
15 
Haemorrhagic events * 
Haemorrhages (SMQ) 
*  Data will be summarized by period and listed after adjudication of those events have been properly investigated 
13.2 
Laboratory assessments – Marked abnormality criteria 
The following criteria will be applied in the determination of marked abnormalities for 
laboratory assessment values. They are based on Version 5 of the CTCAE grade 3 or higher 
criteria. If both high and low criteria are shown for a parameter, the criteria should be 
summarized separately in tabular or graphical data summaries.  
13.2.1 
Hematology 
Table 13-2: Hematology Parameters 
PARAMETER 
UNIT 
(conventiona
l) 
UNIT 
(standard) 
MARKED ABNORMALITY 
CRITERIA 
Hemoglobin  
g/dL 
 
g/L 
<8.0 g/dL; <80 g/L  
WBC (Leukocytes)1 
109/L 
109/L  
Low: <2.0 x 109/L  
High:  >30 x 109/L  
Lymphocytes Absolute 
109/L 
109/L  
Low:  <0.5 x 109/L  
High: >20 x 109/L 
Neutrophils Absolute  
109/L 
109/L  
 <1.0 x 109/L   
Platelets2 
109/L 
109/L  
<50.0 x 109/L  
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1WBC (Leukocytes) markedly abnormal high criterion is not based on Version 5 CTCAE Grade 3 or 
higher criteria. Due to the mechanism of action of RLZ, the safety alert is related to infection risk which 
would be identified by a lower cut-point than the standard which is related to acute leukemias. A 
markedly abnormal high cut-point >30 x 109/L is applied to flag leukocytosis (George 2012). 
2For ITP protocols, platelets will not be assessed for TEMA because this parameter is 
expected to be abnormally low due to the participant population and entry criteria.  
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13.2.2 
Chemistry 
Table 13-3: Chemistry Parameters 
PARAMETER 
UNIT 
(conventional) 
UNIT 
(standard) 
MARKED ABNORMALITY 
CRITERIA 
AST (SGOT) 
U/L 
U/L 
>5.0 x ULN  
ALT (SGPT) 
U/L 
U/L 
>5.0 x ULN  
ALP (Alkaline 
Phosphatase) 
U/L 
U/L 
>5.0 x ULN  
Bilirubin 
(Total) 
mg/dL 
umol/L 
>3.0 x ULN if Baseline value is normal; 
>3.0 x Baseline value if Baseline is 
abnormal  
Albumin 
g/dL 
g/L 
<2 g/dL; <20 g/L  
Creatinine 
mg/dL 
umol/L 
>3.0 x ULN 
Estimate 
glomerular 
filtrate rate 
(eGFR)1 
mL/min/1.73 
m2 
mL/min/1.73 
m2 
eGFR <29 mL/min/1.73 m2 
C reactive 
protein (CRP)2 
mg/L 
mg/L 
>10 mg/dL 
Corrected 
Calcium3 
mg/dL 
mmol/L 
Low: Corrected serum calcium of <7.0 
mg/dL; <1.75 mmol/L 
High: Corrected serum calcium of >12.5 
mg/dL; >3.1 mmol/L 
Potassium 
mmol/L 
mmol/L 
Low: <2.5 mmol/L 
High: >6.0 mmol/L 
Sodium 
mmol/L 
mmol/L 
Low: <125 mmol/L  
High: >155 mmol/L 
Glucose 
mg/dL 
mmol/L 
<40 mg/dL; <2.2 mmol/L  
High: > 250 mg/dL; >13.9 mmol/L 
Total 
Cholesterol 
mg/dL 
mmol/L 
>400 /dl; >10.34 mmol/L  
Triglycerides 
mg/dL 
mmol/L 
>500 mg/dl; >5.7 mmol/L 
Abbreviations: ALT= alanine aminotransferase; AST = aspartate aminotransferase; dL = deciliter; GGT: gamma-
glutamyltransferase; L = liter; mg = milligram; mmol = millimoles; μg = microgram; U = unit; ULN = upper limit of 
normal 
Note: Marked abnormality criteria are defined by Grade 3 or higher events according to the Common Terminology 
for Adverse Events (CTCAE), Version 5.0, November 17, 2017 unless otherwise noted.  
1eGFR is calculated using the Chronic Kidney Disease Epidemiology Collaboration or CKD-EPI formula which is 
eGFR = 141 * min(Scr/κ,1)α * max(Scr/κ, 1)-1.209 * 0.993Age * 1.018 [if female] * 1.159 [if black];  where Scr is 
serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min 
indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. 
2Includes CRP and High Sensitivity (HS) CRP. Reference for marked abnormality criteria: Nehring, S.M.; Goyal, 
A.; Patel, B.C. (2020). StatPearls Publishing, web link: https://www.ncbi.nlm.nih.gov/books/NBK441843/. 
y8 
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3Corrected Calcium is calculated using the formula: Corrected Calcium(mmol/L) =0.02 * (40 – Alb(g/L)) + 
ca(mmol/L). Note that the normal Albumin level is typically assumed to be equal to 40 g/L. 
13.3 
Vital sign assessments - abnormal 
Abnormality criteria to be applied in the assessment of vital signs parameter values are given 
below. 
Table 13-4: Vital Sign Parameters 
PARAMETER 
ABNORMALITY CRITERIA 
Pulse Rate (beats/minute) 
 
<50 and a decrease from Baseline of ≥15 
>120 and an increase from Baseline of ≥15 
Systolic Blood Pressure (mmHg) 
≤90 and a decrease from Baseline of ≥20 
≥180 and an increase from Baseline of ≥20 
Diastolic Blood Pressure (mmHg) 
<50 and a decrease from Baseline of ≥15 
>105 and an increase from Baseline of ≥15 
Temperature 
>101 0F (38.3 0C) 
Body Weight 
 ≥10% decrease from Baseline 
≥10% increase from Baseline 
13.4 
Electrocardiogram (ECG) – Abnormal 
Abnormality criteria to be applied in the assessment of ECG parameter values are given below: 
Table 13-5: ECG Parameters 
Parameter 
Abnormality Criteria 
QT interval (ms) 
≥500ms 
≥60ms increase from Baseline 
QTc(F) (ms) 
>500ms (Corrected) 
>60ms increase from Baseline 
PR interval (ms) 
Treatment-emergent value >200ms 
QRS interval (ms) 
Treatment-emergent value >100ms 
Heart rate (bpm) 
<50bpm 
>120bpm 
Abbreviations: BL= Baseline, bpm = beats per minute; ms = milliseconds; QTc(F) = Fridericia corrected QT 
interval;  
Note: Treatment-emergent is defined as meeting the criteria at any post-Baseline visit during the Treatment Period 
(including unscheduled visits) and not meeting the same criteria during Baseline 
13.5 
ITP-PAQ Scoring 
13.5.1 ITP-PAQ Scales 
Please see below for the items associated for each scale and the number of points in the 
Likert Scale that will be used per scale where higher numbers mean better health status. 
 
Table 13-6: ITP Questions 
Question 
Scale 
Response Categories 
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1 
Physical Health: symptoms  
0-4 
2 
3 
  
4 
  
5 
  
6 
  
7 
Physical Health: fatigue 
0-4 
8 
  
9 
  
10 
  
11 
Physical Health: bother 
0-4 
12 
0-6 
13 
0-6 
14 
Physical Health: activity 
0-4 
15 
0-4 
16 
Emotional Health: psychological 
0-4 
17 
0-4 
18 
0-4 
19 
0-4 
20 
0-4 
21 
Emotional Health: fear 
0-4 
22 
0-4 
23 
0-4 
24 
0-4 
25 
0-4 
26 
Overall QoL 
0-6 
27 
0-6 
28 
0-3 
29 
0-3 
30 
0-3 
31 
Social Activity 
0-4 
32 
0-4 
33 
0-4 
34 
0-4 
35 
Women’s reproductive health 
0-4 
36 
0-4 
37 
0-4 
38 
0-4 
39 
0-4 
40 
0-4 
41 
Work 
0-5 
42 
0-5 
43 
0-5 
44 
0-5 
 
The ITP-PAQ domain scores will be obtained by transforming the raw sum of the item 
responses to a 0-100 scale. This can be obtained using the following formula: 
 
ITP-PAQ score = Sum of  item scores within the scale
raw sum range
∗100 
 
ITP-PAQ domain 
Raw sum range 
Symptoms 
24 
Fatigue 
16 
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Bother 
16 
Activity 
8 
Psychological health 
20 
Fear 
20 
Work 
20 
Social activity 
16 
Women’s reproductive health 
24 
Overall Quality of Life 
21 
 
Missing data: 
A domain score is not calculated if more than half of the items of this domain are missing. 
If 50% or more of the items are available, missing items are imputed using the mean of non-
missing items. For domains that include items with a different number of categories, the imputed 
response for missing items has to be transformed on the range of the response scale of the 
missing item. 
13.6 
ITP bleeding score 
The ITP-BAT tool version 1.0 consists of the following domains: 
− Skin (S) 
− Visible mucosae (M) 
− Organs (O) 
The domain for skin comprises the following bleeding types: 
− Petechiae 
− Ecchymoses 
− Subcutaneous hematomas 
− Bleeding from minor wounds 
The domain for visible mucosae comprises the following bleeding types: 
− Epistaxis 
− Oral cavity- gum bleeding 
− Oral cavity – hemorrhagic bullae or blisters 
− Oral cavity – bleeding from bites to lips and tongue or after deciduous teeth loss 
− Subconjunctival hemorrhage (not due to conjunctival disease) 
The domain for organs comprises the following bleeding types: 
− Gastrointestinal bleeding not explained by visible mucosal bleeding or lesion 
− Lung bleeding 
− Hematuria 
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− Menorrhagia 
− Intramuscular hematomas 
− Hemarthrosis 
− Ocular bleeding 
− Intracranial bleeding 
− Other internal bleeding 
The grading for each bleeding type within each domain is presented in Table 13-7. Each bleeding 
type is graded based on the worst manifestation that occurred during the most recent observation 
period (since the previous visit). The grade for each domain is then taken as the worst (most 
severe) grade across all bleeding types within that domain. 
Missing data will not be imputed. In the case that data for one or more bleeding types are 
missing within a given domain, the grade for that domain will be evaluated based on the 
available data. In the case that no data are available within a given domain, the score for that 
domain will not be evaluated at the specific visit. 
Table 13-7: ITP-BAT scoring  
Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
SKIN 
 
 
 
 
 
Petechiae 
(does not 
include 
steroid–
induced or 
senile 
purpura)  
 No 
 
 Less than 
or equal to 10 
in a patient’s 
palm-sized 
area3 in the 
most affected 
body area4 
 
 More than 
10 in a 
patient’s palm-
sized area or 
more than 5 in 
at least 2 
patient’s palm-
sized areas 
located in at 
least 2 different 
body areas4, 
one above and 
one below the 
belt (in the 
most affected 
body areas) 4 
 
 More 
than 50, if 
scattered 
both above 
and below 
the belt  
 
 
Ecchymoses  
 None or 
up to 2 in the 
same body 
area4, but 
 3 or more 
in the same 
body area4, 
but all smaller 
 From 1 to 5 
larger than a 
patient’s 
palm-sized 
 More 
than 5 larger 
than a 
patient’s 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
smaller than 
a patient’s 
palm-sized 
area, if 
a) 
spontaneous 
or b) 
disproportio
nate to 
trauma/const
riction5 
 
than a 
patient’s 
palm-sized 
area, if 
a) 
spontaneous 
or  
b) 
disproportiona
te to 
trauma/constri
ction5 
 At least 2 
in two 
different body 
areas4, smaller 
than a 
patient’s 
palm-sized 
area, if 
a) 
spontaneous 
or  
b) 
disproportiona
te to 
trauma/constri
ction5 
 Any 
number and 
size if 
reported by 
the patient  
area, if 
a) spontaneous 
or  
b) 
disproportionat
e to 
trauma/constric
tion5 
with or without 
smaller ones 
 
 
palm-sized 
area, if 
a) 
spontaneous 
or  
b) 
disproportio
nate to 
trauma/ 
constriction5 
 
Subcutaneou
s hematomas 
 
 No 
 
 1 smaller 
than a 
patient’s 
palm-sized 
area 
 Any 
number and 
size if 
 2 smaller 
than a patient’s 
palm-sized 
area, 
spontaneous  
 2 smaller 
than a patient’s 
palm-sized 
 More 
than 2 
smaller or at 
least 1 
larger than a 
patient’s 
palm-sized 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
reported by 
the patient 
 
area, 
disproportionat
e to trauma5 
 
area, 
spontaneous  
 More 
than 2 
smaller or at 
least 1 
larger than a 
patient’s 
palm-sized 
area, 
disproportio
nate to 
trauma5 
Bleeding 
from minor 
wounds6  
 No 
 
 Lasting 
<=5 min 
 Any 
episode if 
reported by 
the patient  
 
 Lasting >5 
min or 
interfering with 
daily activities  
 
 
Requiring 
protracted 
medical 
observation 
at the time 
of this visit  
 Medical 
report 
describing 
patient’s 
evaluation 
by a 
physician  
 
MUCOSAL 
 
 
 
 
 
Epistaxis7 
 
 No 
 
 Lasting 
<=5 min 
 Any 
episode if 
reported by 
the patient  
 
 Lasting >5 
min or 
interfering with 
daily activities  
 
 Packing 
or 
cauterizatio
n or 
in-hospital 
evaluation 
at the time 
of this visit  
 Medical 
report 
describing 
packing or 
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
cauterizatio
n or in-
hospital 
evaluation 
Oral cavity – 
gum 
bleeding7 
 No  
 
 
 Lasting 
<=5 min 
 Any 
episode if 
reported by 
the patient 
 
 Lasting >5 
min or 
interfering with 
daily activities  
 
 
Requiring 
protracted 
medical 
observation 
at the time 
of this visit  
 Medical 
report 
describing 
patient’s 
evaluation 
by a 
physician 
 
Oral cavity – 
hemorrhagic 
bullae or 
blisters  
 No 
 
 Less than 
3 
 Any 
number if 
reported by 
the patient 
 
 From 3 to 
10 but no 
difficulty with 
mastication  
 
 More 
than 10 or 
more than 5 
if difficulty 
with 
mastication 
 
Oral cavity - 
bleeding 
from bites to 
lips & tongue 
or after 
deciduous 
teeth loss 
 No 
 
 Lasting 
<=5 min 
 Any 
episode if 
reported by 
the patient  
 
 Lasting >5 
min or 
interfering with 
daily activities 
 
 
 
Intervention
s to ensure 
hemostasis 
or in-
hospital 
evaluation 
at the time 
of this visit 
 Medical 
report 
describing 
intervention
s to ensure 
hemostasis 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
or in-
hospital 
evaluation 
Subconjuncti
val 
hemorrhage  
(not due to 
conjunctival 
disease) 
 No 
 
 Petechiae/ 
hemorrhage 
partially 
involving one 
eye 
 Any 
episode if 
reported by 
the patient  
 
 Petechiae/ 
hemorrhage 
partially 
involving both 
eyes, or diffuse 
hemorrhage in 
one eye  
 
 
 Diffuse 
hemorrhage 
in both eyes 
 
 
ORGAN (and 
internal 
mucosae) 
 
 
 
 
 
 
Gastrointesti
nal bleeding 
not explained 
by visible 
mucosal 
bleeding or 
lesion: 
Hematemesis, 
Melena, 
Hematochezia
, 
Rectorrhagia 
 No 
 
 Any 
episode if 
reported by 
the patient 
  
 Present at 
the visit  
 Described 
in a medical 
report  
 
 
Requiring 
endoscopy8 
or other 
therapeutic 
procedures 
or in-
hospital 
evaluation 
at the time 
of this visit 
 
 Medical 
report 
prescribing 
endoscopy8 
or other 
therapeutic 
procedures 
or in-
hospital 
evaluation 
 
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
Lung 
bleeding 
Hemoptysis 
Tracheobronc
hial bleeding 
 No 
 
 Any 
episode if 
reported by 
the patient 
 
 Present at 
this visit 
 Described 
in a medical 
report  
 
 
Requiring 
bronchosco
py8 or other 
therapeutic 
procedures 
or in-
hospital 
evaluation 
at the time 
of this visit  
 An 
equivalent 
episode if 
described in 
a medical 
report  
 
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
 
Hematuria  
 No 
 
 Any 
episode if 
reported by 
the patient 
 
Microscopic 
(lab analysis 
exhibited) 
 
 
 
Macroscopic 
(lab analysis 
exhibited) 
 
 Described 
in a medical 
report  
 
 
Macroscopi
c, and 
requiring 
cystoscopy8 
or other 
therapeutic 
procedures 
or in-
hospital 
evaluation 
at the time 
of this visit 
 An 
equivalent 
episode if 
described in 
a medical 
report  
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
Menorrhagia 
(compared to 
pre-ITP or to 
 No 
  
 Doubling 
nr. of pads or 
tampons in 
last cycle 
 Changing 
pads more 
frequently than 
every 2 hrs. or 
 Acute 
menorrhagia 
requiring 
hospital 
 RBC 
transfusion 
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Statistical Analysis Plan                            Rozanolixizumab                                                           
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
a phase of 
disease with 
normal 
platelet 
count)9 
 
compared to 
pre-ITP or to 
a phase of 
disease with 
normal 
platelet count 
 Score 
>100 using 
PBAC in the 
last cycle, if 
normal score 
in pre-ITP 
cycles or in a 
phase of 
disease with 
normal 
platelet count 
clot and 
flooding 
 
 Requiring 
combined 
treatment with 
antifibrinolytic
s and hormonal 
therapy or 
gynecological 
investigation 
(either at this 
visit or 
described in a 
medical report)  
admission 
or 
endometrial 
ablation 
(either at 
this visit or 
described in 
a medical 
report)  
 
  
or Hb drop 
>2g/dL  
 
 
Intramuscula
r hematomas 
(only if 
diagnosed by 
a physician 
with an 
objective 
method)  
 
 No 
 
 
 Post 
trauma, 
diagnosed at 
this visit, if 
judged 
disproportiona
te to trauma 
 An 
equivalent 
episode if 
described in a 
medical report  
 
 
Spontaneous, 
diagnosed at 
this visit  
 
 An 
equivalent 
episode if 
described in a 
medical report  
 
 
Spontaneou
s or post 
trauma (if 
judged 
disproportio
nate to 
trauma) 
diagnosed at 
this visit 
and 
requiring 
hospital 
admission 
or surgical 
intervention 
 An 
equivalent 
episode if 
described in 
a medical 
report  
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
 
  
 
Hemarthrosis  
 No  
 
 Post 
trauma, 
 
Spontaneous, 
 
Spontaneou
 
Spontaneou
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
(only if 
diagnosed by 
a physician 
with an 
objective 
method) 
diagnosed at 
this visit, 
function 
conserved or 
minimally 
impaired, if 
judged 
disproportiona
te to trauma 
 An 
equivalent 
episode if 
described in a 
medical report 
diagnosed at 
this visit, 
function 
conserved or 
minimally 
impaired 
 
 An 
equivalent 
episode if 
described in a 
medical report  
 
 
s or post 
trauma (if 
judged 
disproportio
nate to 
trauma), 
diagnosed at 
this visit 
and 
requiring 
immobilizat
ion or joint 
aspiration 
 An 
equivalent 
episode if 
described in 
a medical 
report 
s or post 
trauma (if 
judged 
disproportio
nate to 
trauma) 
diagnosed 
at this visit 
and 
requiring 
surgical 
intervention 
 An 
equivalent 
episode if 
described in 
a medical 
report  
Ocular 
bleeding 
(only if 
diagnosed by 
a physician 
with an 
objective 
method) 
 No 
 
 
 
 
 Any post 
trauma vitreous 
or retinal 
hemorrhage 
involving one 
or both eyes 
with or without 
impaired/blurre
d vision present 
at this visit if 
judged 
disproportionat
e to trauma 
 An 
equivalent 
episode if 
described in a 
medical report  
 
Spontaneou
s vitreous or 
retinal 
hemorrhage 
involving 
one or both 
eyes with 
impaired/bl
urred vision 
present at 
this visit 
 An 
equivalent 
episode if 
described in 
a medical 
report  
 
 
Spontaneou
s vitreous or 
retinal 
hemorrhage 
with loss of 
vision in 
one or both 
eyes present 
at this visit 
 An 
equivalent 
episode if 
described in 
a medical 
report  
 
Intracranial 
bleeding10: 
 No 
 
 
 
 Any post 
trauma event 
 Any 
spontaneous 
event 
 Any 
spontaneous 
event 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
intracerebral, 
intraventricula
r, 
subarachnoida
l, subdural, 
extradural  
(only if 
diagnosed 
with an 
objective 
method at the 
visit or 
described in 
a medical 
report 
provided by 
the patient)  
requiring 
hospitalization  
 
requiring 
hospitalizati
on in 
presence of 
an 
underlying 
intracranial 
lesion 
  
requiring 
hospitalizati
on without 
an 
underlying 
intracranial 
lesion 
 
Other 
internal 
bleeding: 
hemoperitone
um 
hemopericardi
um 
hemothorax 
retroperitoneal 
bleeding 
hepatic and 
splenic 
peliosis with 
organ rupture 
retroorbital 
bleeding 
metrorrhagia 
etc. 
(only if 
diagnosed 
with an 
objective 
method at the 
 No 
 
 
 
 Any 
event 
requiring 
hospitalizati
on <48 hrs. 
 
 Any 
event 
requiring 
hospitalizati
on >48 hrs. 
or RBC 
transfusion 
or Hb drop 
>2g/dL  
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
visit or 
described in 
a medical 
report 
provided by 
the patient)  
Grading is based on physical examination at the time of the visit by the physician or expert nurse or on patient’s 
history supplemented by available medical reports. Bleeding manifestations reported by the patient but not visible at 
the time of data collection are graded 1. Grade 5 is assigned to fatal bleeding. 
To receive a grade >1, all non-overt skin and non-overt mucosal bleeding (petechiae, ecchymoses, subcutaneous 
hematomas, vesicles/bullae subconjunctival bleeding) should be visible at the time of visit for grading by the 
physician or expert nurse taking the history.  
For bleeding from minor wounds and overt-mucosal bleeding (epistaxis, gum, bleeding from bites to lips & tongue 
or after deciduous teeth loss/extraction) and all organ bleeding, a medical record describing the symptom or 
indicating a specific intervention/prescription should be also taken into account for grading.  
Requirement for ITP-specific treatments and anti-fibrinolytics (apart from menorrhagia) was not considered for 
grading, due to their subjective nature and their adoption not only to control actual bleeding but also to reduce the 
“risk” of impendent or future bleeding.  
1 In case of patients examined for the first time, all types of bleeding occurring at the visit and in the 15 days 
preceding the visit should be considered.  
2 Each type of bleeding should be graded based on the worst bleeding manifestation that occurred during each 
observation period or in the 15 days preceding the first visit. 
3 Patient’s own palm size is commonly considered to be proportional to body surface area. Palm = the inner 
surface of the hand stretching between the distal crease of the wrist and the bases of the fingers (fingers surface 
excluded). 
4 Body areas include: face, neck, right and left upper limbs (considered separately), right and left lower limbs 
(considered separately), trunk, abdomen, and recumbent areas (for the ambulatory patient means the area below 
the knees).  
5 Bleedings considered proportionate to trauma/constriction on a clinical ground should not be reported for skin 
domain. 
6 Minor wound means superficial skin cuts (eg, by shaving razor, knife, or scissors). 
7 Epistaxis and gum bleeding are also reported in some normal subjects. Thus, a critical judgment is required in 
grading these manifestations; they should be reported only if judged more severe when compared with pre-ITP 
bleeding, if any. 
8 Any endoscopic investigations should be considered for grading only if performed for therapeutic purpose and 
not solely for diagnostic purpose. 
9 In girls at menarche grade 1 cannot be assigned, lacking comparison with previous cycles. 
10 Intracranial bleeding should always be reported, irrespective of its grade. For example, if a woman had S2 
(subcutaneous hematoma) M2 (epistaxis) O3 (menorrhagia) and an intracranial bleeding grade 2 (post trauma, 
requiring hospitalization), the SMOG index is S2M2O3 (intracranial 2). If the same patient also had intracranial 
bleeding grade 3, the SMOG index is S2M2O3 (intracranial 3). 
 
 
 
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13.7 
Classification of the SF-36v2 questionnaire 
Table 13-8: SF-36V2 Questions 
Scales 
Physical Functioning 
Role-Physical 
Bodily Pain 
General Health 
Vitality 
Social Functioning 
Role-Emotional 
Mental Health 
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Page 73 of 76 
14 
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN 
(SAP) 
14.1 
AMENDMENT 1 
 Rationale for the amendment 
The primary reason for this SAP amendment is to incorporate the changes from Protocol 
Amendment 4 and the reduced scope of analyses following sponsor’s decision to terminate the 
study early. 
Table 14-1: Modifications and changes 
Section # and Name 
Description of Change 
Brief Rationale 
2.1.3 
Removed objective “To evaluate the 
effects of rozanolixizumab on exploratory 
biomarkers” 
Updated to align with 
Protocol Amendment 4 
2.1.3 
Added objective “To assess the effect of 
rozanolixizumab on response to 
vaccination in study participants who 
received COVID-19 vaccine” 
2.2.2.4 
Removed “Including all intermediate 
timepoints” from ITP-PAQ endpoint 
2.2.3.4 
Changed text of IgG, IgA, IgE and IgM 
endpoints 
2.2.3.5 
Removed ITP-specific autoantibodies 
endpoint 
2.2.3.7 
Removed several exploratory endpoints 
2.2.3.7 
Added COVID-19 vaccination endpoint 
2.2.1.2 
Removed α-globulin, and β-globulin 
endpoints 
2.2.1.2 
Removed Cytokines endpoint 
2.3 
Removed the exploratory arm 
2.3 
Dosing is
 instead of
 
2.3 
Various other changes to study design that 
do not have a direct impact on analysis 
3.2.4 
Definition of dosing regimen groups 
(
 and 
 
Need to define subsets of 
protocol-defined analysis 
sets which will be used for 
analysis 
3.5.4 
Change complete infusion to sufficient 
infusion 
Requested by FDA 
3.7 
Updated to MedDRA version 24 dictionary 
New version available 
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Section # and Name 
Description of Change 
Brief Rationale 
3.7 
Updated to WHODD, Mar 2021 version  
New version available 
3.8 
Text added to describe analysis omitted 
because of early termination of study.  
Sponsor decision to 
terminate study early. 
4.1 
Text referring to sensitivity analysis and 
MI MAR analysis removed. 
Analysis no longer 
required. 
4.1.3 
Changed intercurrent event strategy for 
COVID-19 to composite strategy and 
platelet data set to 0 
Requested by FDA 
6.5.1 
Modification to assignment of medications 
to treatment period 
Be consistent with the 
definition of treatment 
period 
 
9.1.1 
 
Analysis has been removed. 
Owing to the sponsor’s 
decision to terminate this 
study the analysis is no 
longer required. 
 
9.2.2 – 9.2.4, 9.2.6 – 9.2.7 
Analysis has been removed. 
9.3 
Analysis has been removed. 
9.4 
Analysis has been removed. 
 
9.2.1 
 
All formal statistical analysis has been 
removed  
11.2.1 
Text modified to reflect that item responses 
will be listed only, no derived scores will 
be calculated, and no change from baseline 
will be computed. 
11.2.2 
Text added to reflect that item responses 
will be listed only, no derived scores will 
be calculated, and no change from baseline 
will be computed. 
10.2 
Updated the analysis for antidrug 
antibodies 
Owing to the sponsor’s 
decision to terminate this 
study the majority of the 
analysis is no longer 
required. 
10.3.1 – 10.3.3 
Changed text of IgG, IgA, IgE and IgM 
endpoints 
Updated to align with 
Protocol Amendment 4 
10.3.2, 10.4.3 
Removed ITP-specific autoantibodies 
endpoint 
10.5 
Removed several exploratory endpoints 
8.6 
Clarified definition for time at risk 
Align with TP0003/6 
definition 
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Section # and Name 
Description of Change 
Brief Rationale 
 
8.2 
Clarified definitions of severity and 
intensity for adverse events 
Clarify how severe adverse 
events will be summarized 
8.2.2 
Add AESIs and TEAEs leading to study 
discontinuation to overview 
Categories in overview 
should match categories in 
adverse event tables 
8.2.2 
Removed some adverse event tables 
No longer needed 
8.2.2 
Added AEs of focus: hemorrhagic events, 
worsening thrombocytopenia and effect on 
lipids 
These were added to the 
AE of Focus document 3.0, 
or they were removed from 
the document but were still 
considered relevant for ITP 
8.5.1 
Added “All values must be met at the same 
sample taken from the same visit” 
Clarified how PDILI is 
defined 
8.5.1 
Added the components of the Hy’s law 
definition presented separately in a 
stepwise fashion to the table 
Provide more information 
about the components of 
PDILI 
8.7 
Removed α-globulin, and β-globulin 
endpoints 
Updated to align with 
Protocol Amendment 3 
8.8 
Removed change from baseline for 
Complement endpoint 
Owing to the sponsor’s 
decision to terminate this 
study the analysis is no 
longer required. 
8.9 
Removed Cytokines endpoint 
Updated to align with 
Protocol Amendment 3 
Throughout 
Minor editorial and formatting changes 
have been made. 
Minor, therefore have not 
been summarized. 
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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:
tp0004-sap-amend-1
Version:
1. 0
Document Number:
CLIN-000184838
Title:
TP0004 SAP Amendment 1
Approved Date:
21 Oct 2022
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 21-Oct-2022 21:02:16 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 21-Oct-2022 21:23:55 GMT+0000
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