Conditions: Healthy Study Participants
Keywords: Healthy Study Participants Phase 1 rozanolixizumab manual push syringe driver
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 32
Healthy volunteers: yes

Brief summary:
The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single subcutaneous (SC) dose of rozanolixizumab administered to healthy participants by manual push (MP) versus (vs) syringe driver.

Detailed description:

Arms:
arm 1: Study participants randomized to Cohort 1 will receive a single dose of rozanolixizumab (RLZ) or placebo (PBO) subcutaneously administered with a syringe driver. arm 2: Study participants randomized to Cohort 2 will receive a single dose of rozanolixizumab (RLZ) or placebo (PBO) subcutaneously administered by manual push. arm 3: Study participants randomized to Cohort 3 will receive a single dose of rozanolixizumab (RLZ) or placebo (PBO) subcutaneously administered with a syringe driver. arm 4: Study participants randomized to Cohort 4 will receive a single dose of rozanolixizumab (RLZ) or placebo (PBO) subcutaneously administered by manual push.

Interventions: intervention 1: rozanolixizumab intervention 2: Placebo
Intervention descriptions: intervention 1: Study participants will receive a single dose rozanolixizumab subcutaneously administered by manual push or a syringe driver. intervention 2: Study participants will receive a single dose placebo subcutaneously administered by manual push or a syringe driver.

Protocol document:
Prot_000.pdf: 
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PROTOCOL UP0106 AMENDMENT 2 
A RANDOMIZED, PARTICIPANT-BLIND, 
INVESTIGATOR-BLIND, PLACEBO-CONTROLLED STUDY TO 
EVALUATE THE SAFETY, TOLERABILITY, 
PHARMACOKINETICS, AND PHARMACODYNAMICS OF 
ROZANOLIXIZUMAB ADMINISTERED SUBCUTANEOUSLY 
VIA MANUAL PUSH VERSUS SYRINGE DRIVER TO HEALTHY 
PARTICIPANTS 
PHASE 1 
SHORT TITLE: 
A Phase 1 study comparing the safety, tolerability, pharmacokinetics, and pharmacodynamics of 
subcutaneous rozanolixizumab administered via manual push vs syringe driver to healthy 
participants 
Sponsor: 
UCB Pharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying number(s): 
Eudra CT Number: 
2020-005973-28 
NCT Number 
NCT04828343 
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 2 
03 Jun 2021 
Substantial 
Protocol Amendment 1 
16 Mar 2021 
Non-substantial 
Original protocol 
04 Feb 2021 
Not applicable 
Amendment 2 (03 Jun 2021) 
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. 
Overall Rationale for the Amendment 
The primary reason for this protocol amendment is to add 2 time points for the clinical chemistry 
assessment, at 6 hours and 12 hours after the start of infusion. Additionally, the minimum time 
period between COVID-19 vaccination and the Screening Visit has been clarified, and one 
exploratory endpoint has been updated. Other changes include the addition of respiratory rate to 
the list of vital signs and phosphate to the list of clinical chemistry parameters. Additional 
updates have been incorporated to provide further clarity on the protocol and/or to correct errors. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
3 Objectives and endpoints 
The exploratory endpoint/estimand 
“Exact volume of IMP 
administration, determined by 
syringe and infusion line weights” 
has been changed to “Volume of 
IMP administration.” 
To reflect the change in the method 
used to assess the volume of IMP 
administration. The volume of IMP 
infused will be based on the 
volume (mL) indicated by the 
graduations on the syringe. 
1.3 Schedule of activities  
Table 1-1: Added 2 time points for 
the clinical chemistry assessment, 
at 6 and 12 hours after the start of 
infusion. 
To ensure adequate monitoring of 
clinical chemistry parameters 
during the first 24 hours after the 
start of infusion.  
1.3 Schedule of activities 
8.9 Biomarkers 
10.2 Appendix 2: Clinical 
laboratory tests 
Table 1-1, Table 1-2, text in 
Section 8.9, and footnote d of 
Protocol-Required Safety 
Laboratory Assessments table have 
been updated.  
Corrected to clarify that 
complement and cytokine sampling 
are taken at 4 and 8 hours post 
event, only if an infusion reaction 
or AE of special monitoring is 
observed.  
1.3 Schedule of activities 
Table 1-1: Footnote i has been 
updated to clarify that vital signs 
are also assessed predose. 
Updated to be consistent with the 
study design.  
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Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of activities 
8.2.2 Vital signs 
9.4.1.3 Vital signs and 
electrocardiograms 
Table 1-1: Footnote i and text in 
Section 8.2.2 and Section 9.4.1.3 
have been updated to add 
respiratory rate to the list of vital 
signs. 
For consistency with the following 
other safety endpoint “Vital signs 
measurements (blood pressure, 
pulse rate, respiratory rate, and 
body temperature), 12-lead 
electrocardiogram, and local 
tolerability assessments at each 
scheduled assessment during the 
In-Clinic and SFU Periods.” 
1.3 Schedule of activities 
Table 1-1: Footnote i has been 
updated to remove “at the start of 
infusion.” 
There is no 12-lead ECG 
assessment at the start of infusion 
in this study.  
1.3 Schedule of activities 
8.2.5 Local tolerability 
Table 1-1: Footnote m and text in 
Section 8.2.5 have been updated to 
clarify that the assessment of local 
tolerability of SC infusion for the 
“0” time point will be completed 
predose. The time point “at the end 
of infusion” has also been added.  
Updated to be consistent with the 
study design.  
1.3 Schedule of activities 
8.9 Biomarkers 
Table 1-1: Footnote t and text in 
Section 8.9 have been updated to 
clarify that backup samples could 
be stored for later biomarker 
analyses (up to 20 years). 
Updated to provide further 
clarification.  
1.3 Schedule of activities 
Table 1-1: A new footnote has 
been added, Footnote u: 
Anti-rozanolixizumab antibodies 
will be assessed predose and on 
Days 10, 16, 22, and 57.  
Added to clarify the 
anti-rozanolixizumab antibodies 
sampling time points.  
2.3 Benefit/risk assessment The text has been updated to 
clarify the mechanism of action of 
rozanolixizumab with respect to 
COVID-19 vaccination.  
Added to clarify the potential 
interaction between COVID-19 
vaccine and the IMP.  
2.3 Benefit/risk assessment 
8.2.12 COVID-19 
precautions 
The text has been updated to 
clarify that the Screening Visit 
should not be scheduled before at 
least 2 weeks after the COVID-19 
vaccination. 
Added to clarify the minimum time 
period between COVID-19 
vaccination and the Screening 
Visit. 
6.5.2 Prohibited 
concomitant treatments 
(medications and 
therapies) 
The text has been updated to 
clarify that vitamins are permitted 
during the study. 
To clarify that vitamins are 
permitted during the study. 
10.2 Appendix 2: Clinical 
laboratory tests 
Phosphate has been added to the 
list of clinical chemistry 
parameters. 
For consistency with related 
studies.  
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Section # and Name 
Description of Change 
Brief Rationale 
Global 
Minor formatting changes have 
been made. 
Minor, therefore have not been 
summarized. 
 
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SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h) 
Fax 
Europe and Rest of the World: +32 238 66561 
Email 
PSRapidalert@ucb.com 
Phone 
UCB Study Physician: +44 (0) 1753 443 290 
24h Rapid Response Helpline: +44 808 164 0230 
 
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TABLE OF CONTENTS 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ...................................... 2 
1 
PROTOCOL SUMMARY ............................................................................................... 11 
1.1 
Synopsis ....................................................................................................................... 11 
1.2 
Schema ......................................................................................................................... 16 
1.3 
Schedule of activities ................................................................................................... 16 
2 
INTRODUCTION ........................................................................................................... 22 
2.1 
Study rationale ............................................................................................................. 23 
2.2 
Background .................................................................................................................. 24 
2.3 
Benefit/risk assessment ................................................................................................ 25 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 26 
4 
STUDY DESIGN ............................................................................................................. 29 
4.1 
Overall design .............................................................................................................. 29 
4.2 
Scientific rationale for study design ............................................................................ 30 
4.3 
Justification for dose .................................................................................................... 31 
4.4 
End of study definition................................................................................................. 31 
5 
STUDY POPULATION .................................................................................................. 31 
5.1 
Inclusion criteria .......................................................................................................... 31 
5.2 
Exclusion criteria ......................................................................................................... 32 
5.3 
Lifestyle restrictions..................................................................................................... 35 
5.3.1 
Meals and dietary restrictions .............................................................................. 35 
5.3.2 
Caffeine, alcohol, and tobacco ............................................................................. 36 
5.3.3 
Activity ................................................................................................................ 36 
5.4 
Screen failures .............................................................................................................. 36 
6 
STUDY TREATMENTS ................................................................................................. 36 
6.1 
Treatments administered .............................................................................................. 36 
6.1.1 
Administration methods ....................................................................................... 37 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 37 
6.2.1 
Drug accountability ............................................................................................. 38 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 38 
6.3.1 
Procedures for maintaining and breaking the treatment blind ............................. 39 
6.3.1.1 
Maintenance of study treatment blind ....................................................... 39 
6.3.1.2 
Breaking the treatment blind in an emergency situation ........................... 39 
6.4 
Treatment compliance .................................................................................................. 40 
6.5 
Concomitant medication(s)/treatment(s) ..................................................................... 40 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 40 
6.5.2 
Prohibited concomitant treatments (medications and therapies) ......................... 40 
6.5.3 
Rescue medication ............................................................................................... 40 
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6.6 
Dose modification ........................................................................................................ 40 
6.7 
Criteria for study hold or dosing stoppage ................................................................... 40 
6.7.1 
Stopping rules for all cohorts ............................................................................... 41 
6.8 
Treatment after the end of the study ............................................................................ 42 
7 
DISCONTINUATION OF STUDY MEDICATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 42 
7.1 
Discontinuation of study medication ........................................................................... 42 
7.1.1 
Hypersensitivity stopping criteria ........................................................................ 42 
7.1.2 
Liver chemistry stopping criteria ......................................................................... 42 
7.1.3 
QTc stopping criteria ........................................................................................... 43 
7.2 
Participant discontinuation/withdrawal from the study ............................................... 43 
7.3 
Lost to follow-up.......................................................................................................... 44 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 45 
8.1 
Efficacy assessments .................................................................................................... 45 
8.2 
Safety assessments ....................................................................................................... 45 
8.2.1 
Physical examination ........................................................................................... 45 
8.2.2 
Vital signs ............................................................................................................ 45 
8.2.3 
Electrocardiograms .............................................................................................. 46 
8.2.4 
Clinical safety laboratory assessments ................................................................ 46 
8.2.5 
Local tolerability .................................................................................................. 46 
8.2.6 
Self-injection assessment questionnaire .............................................................. 47 
8.2.7 
Injection site reaction questionnaire .................................................................... 47 
8.2.8 
Injection site pain visual analog scale.................................................................. 47 
8.2.9 
QuantiFERON Test ............................................................................................. 47 
8.2.10 
Tuberculosis signs and symptoms questionnaire ................................................. 47 
8.2.11 
Infusion site photographs ..................................................................................... 47 
8.2.12 
COVID-19 precautions ........................................................................................ 47 
8.3 
AEs and SAEs .............................................................................................................. 48 
8.3.1 
Time period and frequency for collecting AE and SAE information .................. 48 
8.3.2 
Method of detecting AEs and SAEs .................................................................... 49 
8.3.3 
Follow-up of AEs and SAEs ................................................................................ 49 
8.3.4 
Regulatory reporting requirements for SAEs ...................................................... 49 
8.3.5 
Pregnancy ............................................................................................................ 49 
8.3.6 
Adverse events of special interest ........................................................................ 50 
8.3.7 
Adverse events of special monitoring .................................................................. 50 
8.3.7.1 
Severe headache ........................................................................................ 50 
8.3.7.2 
Moderate or severe diarrhea ...................................................................... 51 
8.4 
Safety signal detection ................................................................................................. 51 
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8.5 
Treatment of overdose ................................................................................................. 52 
8.6 
Pharmacokinetics ......................................................................................................... 52 
8.7 
Genetics........................................................................................................................ 52 
8.8 
Pharmacodynamics ...................................................................................................... 53 
8.9 
Biomarkers ................................................................................................................... 53 
8.9.1 
Immunogenicity assessments ............................................................................... 53 
8.10 
Medical resource utilization and health economics ..................................................... 53 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 53 
9.1 
Definition of analysis sets ............................................................................................ 53 
9.2 
General statistical considerations ................................................................................. 54 
9.3 
Planned efficacy/outcome analyses ............................................................................. 54 
9.4 
Planned safety and other analyses................................................................................ 54 
9.4.1 
Safety analyses ..................................................................................................... 54 
9.4.1.1 
Adverse events .......................................................................................... 54 
9.4.1.2 
Clinical laboratory tests ............................................................................. 55 
9.4.1.3 
Vital signs and electrocardiograms ........................................................... 55 
9.4.1.4 
Physical examinations ............................................................................... 55 
9.4.2 
PK analyses .......................................................................................................... 55 
9.4.3 
PD analyses .......................................................................................................... 56 
9.4.4 
Other analyses ...................................................................................................... 56 
9.5 
Handling of protocol deviations................................................................................... 56 
9.6 
Handling of dropouts or missing data .......................................................................... 56 
9.7 
Planned interim analysis and data monitoring ............................................................. 56 
9.8 
Determination of sample size ....................................................................................... 57 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 58 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ......................... 58 
10.1.1 
Regulatory and ethical considerations ................................................................. 58 
10.1.2 
Financial disclosure ............................................................................................. 58 
10.1.3 
Informed consent process .................................................................................... 59 
10.1.4 
Data protection ..................................................................................................... 59 
10.1.5 
Committees structure ........................................................................................... 59 
10.1.6 
Data quality assurance ......................................................................................... 60 
10.1.6.1 
Electronic case report form completion .................................................... 60 
10.1.7 
Source documents ................................................................................................ 60 
10.1.8 
Study and site closure .......................................................................................... 61 
10.1.9 
Publication policy ................................................................................................ 61 
10.2 
Appendix 2: Clinical laboratory tests .......................................................................... 62 
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10.3 
Appendix 3: Adverse events – definitions and procedures for recording, evaluating, 
follow-up, and reporting .............................................................................................. 64 
10.3.1 
Definition of AE .................................................................................................. 64 
10.3.2 
Definition of SAE ................................................................................................ 65 
10.3.3 
Recording and follow-up of AE and/or SAE ....................................................... 66 
10.3.4 
Reporting of SAEs ............................................................................................... 68 
10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ......... 69 
10.4.1 
Definitions ........................................................................................................... 69 
10.4.1.1 
Woman of childbearing potential .............................................................. 69 
10.4.2 
Contraception guidance ....................................................................................... 69 
10.4.2.1 
Male participants ....................................................................................... 69 
10.4.2.2 
Pregnancy testing ...................................................................................... 71 
10.4.2.3 
Collection of pregnancy information......................................................... 72 
10.5 
Appendix 5: Genetics ................................................................................................... 73 
10.6 
Appendix 6: Liver safety – suggested actions and follow-up assessments ................. 74 
10.7 
Appendix 7: Medical device AEs, ADEs, SAEs, and device deficiencies: definition 
and procedures for recording, evaluating, follow-up, and reporting ........................... 77 
10.8 
Appendix 8: Rapid alert procedures ............................................................................ 78 
10.9 
Appendix 9: Country specific requirements ................................................................ 80 
10.10 Appendix 10: Abbreviations and trademarks .............................................................. 81 
10.11 Appendix 11: Protocol amendment history ................................................................. 83 
10.12 Appendix 12: Suggested management guidelines for infusion reactions .................... 85 
10.13 Appendix 13: Management of anaphylaxis ................................................................. 86 
11 REFERENCES ................................................................................................................ 87 
SPONSOR DECLARATION .................................................................................................. 88 
 
LIST OF TABLES 
Table 1-1: 
Schedule of activities ....................................................................................... 17 
Table 1-2: 
Additional study assessments .......................................................................... 21 
Table 3-1: 
Study objectives and endpoints ........................................................................ 26 
Table 6-1: 
Study treatments............................................................................................... 37 
Table 10-1: 
Highly effective contraceptive methodsa ......................................................... 71 
Table 10-2: 
Phase 1 liver chemistry stopping criteria and follow-up assessments ............. 75 
 
LIST OF FIGURES 
Figure 1-1: 
Study schematic ............................................................................................... 16 
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Figure 7-1: 
Liver chemistry stopping algorithm ................................................................. 43 
 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: 
A randomized, participant-blind, investigator-blind, placebo-controlled study to evaluate the 
safety, tolerability, pharmacokinetics, and pharmacodynamics of rozanolixizumab administered 
subcutaneously via manual push versus syringe driver to healthy participants 
Short Title: 
A Phase 1 study comparing the safety, tolerability, pharmacokinetics, and pharmacodynamics of 
subcutaneous rozanolixizumab administered via manual push vs syringe driver to healthy 
participants 
Rationale: 
For chronic diseases requiring long-term or life-long therapies, alternate modes of subcutaneous 
(SC) dosing broaden patient options for ease of use and flexibility in how they can conduct their 
drug by self-administration. The manual push (MP) technique (also referred to as "rapid push") 
is a well-established mode of self-administration of SC immunoglobulin G (IgG), which offers 
the advantages of independence from constant use of a syringe driver, reduced infusion times 
(median 
 for abdominal sites), as well as reduced material costs 
(Bienvenu et al, 2018). Currently, in clinical studies, SC administration of rozanolixizumab 
occurs via a programmable syringe driver at a targeted 
. To enable an 
alternative to SC dosing via a syringe driver, there is considerable clinical interest in the 
possibility of employing the MP method for rozanolixizumab, particularly in light of the 
relatively low volumes involved in rozanolixizumab therapy for adults as well as the low 
volumes involved in treating pediatric patients. The current study aims to generate and 
characterize safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles, 
including between-participant variability for the MP technique compared with the currently used 
programmable syringe driver, in the SC dosing of rozanolixizumab. 
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Objectives and Endpoints 
Objectives 
Endpoints/Estimands 
Primary 
• To evaluate the safety and tolerability of a 
 SC dose of rozanolixizumab 
administered to healthy participants by 
MP vs syringe driver 
• Incidence of TEAEs 
Secondary 
• To assess the PK and PD of a 
 SC 
dose of rozanolixizumab administered by 
MP vs syringe driver 
PK endpoints: 
• Cmax, tmax, AUC(0-t) 
PD endpoints: 
• Baseline-corrected area under the Total 
IgG-time curve 
• Rmin 
• tmin 
Exploratory 
• To compare the PK and PD of a 
 SC 
dose of rozanolixizumab administered by 
MP vs syringe driver 
• PK comparisons: Cmax, AUC(0-t) 
• PD comparison: Baseline-corrected Total 
IgG AUC 
• To evaluate the immunogenicity of 
rozanolixizumab following SC 
administration 
• Anti-rozanolixizumab antibody screening 
status (positive or negative screen), 
confirmatory status (positive or negative 
immunodepletion), and the titer for 
“positive immunodepletion” samples at 
each scheduled assessment during the 
In-Clinic and SFU Periods 
• To evaluate the effects of 
rozanolixizumab on the concentrations of 
IgG on tetanus, influenza A virus-specific 
IgG antibody, and COVID-19 
vaccinated/previously infected 
participants 
• Values and change from Baseline in 
serum IgG concentrations at each 
scheduled assessment during the In-Clinic 
and SFU Periods 
• Values and change from Baseline in 
tetanus, influenza A virus-specific IgG 
antibodies, and COVID-19 
vaccinated/previously infected 
participants during the In-Clinic and SFU 
Periods 
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Objectives 
Endpoints/Estimands 
• To assess total volume, total time, and 
infusion rate for MP and syringe driver 
• Volume of IMP administration 
• Time from start to completion and 
resultant infusion rate of IMP 
administration 
• Time of infusion setup for both modes of 
administration 
• To assess acceptability of SC 
rozanolixizumab administration by MP vs 
syringe driver 
• Postdose infusion site pain visual analog 
scale with IMP administration 
• To assess the experience with SC 
infusions 
• Pre- and postdose SIAQ for MP 
administration 
• Postdose ISRQ for syringe driver 
administration 
Other Safety 
• To evaluate changes from Baseline in 
vital signs, 12-lead electrocardiogram, 
and laboratory measurements following 
 doses of rozanolixizumab 
administered by SC MP vs syringe driver 
in healthy study participants 
• Vital signs measurements (blood pressure, 
pulse rate, respiratory rate, and body 
temperature), 12-lead electrocardiogram, 
and local tolerability assessments at each 
scheduled assessment during the In-Clinic 
and SFU Periods 
• Changes from Baseline in clinical 
laboratory assessments will consist of 
hematology including coagulation, clinical 
chemistry, and urinalysis at each 
scheduled assessment during the In-Clinic 
and SFU Periods 
• To further evaluate the safety and 
tolerability of a 
 SC dose of 
rozanolixizumab administered to healthy 
participants by MP vs syringe driver 
• Occurrence of serious TEAEs 
• Occurrence of treatment-related TEAEs 
• Occurrence of TEAEs leading to 
withdrawal 
• Occurrence of AEs of special monitoring 
• Comparison of TEAEs for MP vs syringe 
driver 
• Serum complement (C3, C4), and 
cytokines and plasma complement 
(C3a, C5a) 
AE=adverse event; AUC=area under the concentration-time curve; AUC(0-t)=area under the concentration-time 
curve from 0 to time t; Cmax=maximum plasma concentration; COVID-19=coronavirus disease-19; 
IgG=immunoglobulin G; IMP=investigational medicinal product; ISRQ=injection site reaction questionnaire; 
MP=manual push; ISRQ=injection site reaction questionnaire; PD=pharmacodynamic(s); 
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Objectives 
Endpoints/Estimands 
PK=pharmacokinetic(s); Rmin=maximum decrease in total plasma IgG; SC=subcutaneous(ly); SFU=Safety 
Follow-Up; SIAQ=self-injection assessment questionnaire; TEAE=treatment-emergent adverse event; tmax=time 
to maximum plasma concentration; tmin=time to minimum IgG level 
Overall Design 
This Phase 1 study is a randomized, participant-blind, investigator-blind, placebo-controlled 
safety/tolerability, PK, and PD evaluation of a 
 rozanolixizumab SC dose administered to 
healthy participants by either a programmed syringe driver or by MP via self-administration. As 
rozanolixizumab has not been administered SC to humans by MP, this study represents a 
preliminary assessment of the MP method prior to recommendation of this administration 
technique in the clinical dosing of rozanolixizumab. 
Participants will be divided into 2 body weight categories: ≥35 to <50kg and ≥50kg. Within the 
higher body weight category, 16 participants will be randomly allocated to syringe driver or MP 
cohorts and, subsequently, to rozanolixizumab or placebo. Due to the paucity of clinical data for 
 in the lower body weight range, the primary rozanolixizumab dose for assessment in this 
study is 
 as a dose level for adults weighing ≥35kg to 50kg. A 
 dose is also being 
assessed in low body weight participants to support future rozanolixizumab pediatric 
development programs. Within the lower body weight category, the first eight subjects will 
receive either 
 rozanolixizumab or placebo via syringe driver, and the following 8 subjects 
will receive either 
 rozanolixizumab or placebo via MP. 
The specific treatments administered to each cohort are described below. Two sentinel study 
participants (1 active + 1 placebo) will be incorporated into Cohort 1 and a Safety Monitoring 
Committee (SMC) will convene to evaluate all available safety and tolerability data following 
completion of the 72-hour evaluation period and prior to dosing of the remaining participants in 
Cohort 1. As a further precautionary step for Cohort 1, dosing of the 6 post-sentinel participants 
will be staggered such that no more than 2 participants will be dosed in a 72-hour period with a 
minimum of 48 hours between participants. In addition, the Rapid Alert process is in place 
throughout the study to ensure that exposure to the study medication is stopped if a reported 
event meets the stopping criteria (see Appendix 8 [Section 10.8]). 
Two sentinel study participants (1 active + 1 placebo) will also be incorporated into Cohorts 2 
and 4. Based on review of 48-hour post dose safety and tolerability data by the SMC, dosing will 
commence in remaining participants. Even if the stopping criteria, as outlined in Section 7, are 
not met, it is still at the discretion of the SMC not to proceed to the further dosing. More details 
will be provided in the SMC Charter. 
The eligibility of study participants will be determined during a Screening Period of up to 
4 weeks (Day -28 to Day -2). Once eligibility is confirmed, the study participant will be admitted 
to the site (at Day -1 or the evening of Day -2) and will enter an In-Clinic Period through Day 5. 
Each study participant will receive a 
 SC dose of rozanolixizumab on Day 1 and may be 
discharged beginning at Day 5 at the discretion of the investigator. Each participant will only 
receive  investigational medicinal product (IMP) administration. 
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Beginning at Day 6, study participants will be ambulant and will attend the clinical site for study 
visits through Day 57 to allow sufficient time for systemic IgG levels to return to Baseline and 
for the assessment of anti-drug antibodies. 
Number of Participants 
Approximately 32 participants will be randomly assigned to study medication such that at least 
6 evaluable participants per cohort are expected to complete the study. 
Treatment Groups and Duration 
The treatment groups are planned to be as follows: 
• Cohort 1 (participants with a body weight of ≥35kg to <50kg) is planned to have 
6 participants receive rozanolixizumab 
 and 2 participants receive placebo via syringe 
driver at a 
. 
• Cohort 2 (participants with a body weight of ≥35kg to <50kg) is planned to have 
6 participants receive rozanolixizumab 
 and 2 participants receive placebo via MP 
through self-administration at a 
. 
• Cohort 3 (participants with a body weight of ≥50kg) is planned to have 6 participants receive 
rozanolixizumab 
 and 2 participants receive placebo via syringe driver at a 
 
. 
• Cohort 4 (participants with a body weight of ≥50kg) is planned to have 6 participants receive 
rozanolixizumab 
 and 2 participants receive placebo via MP through 
self-administration at a 
. 
The total maximum study duration per study participant is up to 12 weeks. This includes a 
4-week Screening Period, a 5-day In-Clinic Period, and an ambulatory Safety Follow-Up Period 
from Day 6 through Day 57. 
 
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1.2 
Schema 
A schematic diagram of the study is provided in Figure 1-1. 
Figure 1-1: Study schematic 
 
PBO=placebo; RLZ=rozanolixizumab 
Note: * Includes 2 sentinel participants (1 RLZ + 1 PBO). 
1.3 
Schedule of activities 
The Schedule of Activities is presented in Table 1-1. 
 
Safety 
Follow-up 
Day 57 ± 2 
Ambulatory Days 6 to 57 
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Table 1-1: 
Schedule of activities 
Assessments 
Screening 
Period 
In-Clinic Period 
Ambulatory Period 
 
SFU/WD 
Admission 
Dosing 
Weeks 
-4 to -1 
0 
1 
1 
2 
2 
3 
3 
4 
5 
7 
8 
Days 
-28 to -2 
-1a 
1 
2 
3 
4 
5b 
7 
10 
13 
16 
19 
22 
29 
43 
57 
Hours 
 
 
0 
4 
6 
8 
12 
24 
48 
72 
96 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomizationc 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP administrationd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SARS-CoV-2 testing (PCR) 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
Influenza, tetanus, and 
SARS-CoV-2 antibody 
assessment 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
Study participant carde 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/procedure history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationf 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
Pregnancy testg 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Serum FSH levelh 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tuberculosis test and 
questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol urine test and urine 
drug screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 1-1: 
Schedule of activities 
Assessments 
Screening 
Period 
In-Clinic Period 
Ambulatory Period 
 
SFU/WD 
Admission 
Dosing 
Weeks 
-4 to -1 
0 
1 
1 
2 
2 
3 
3 
4 
5 
7 
8 
Days 
-28 to -2 
-1a 
1 
2 
3 
4 
5b 
7 
10 
13 
16 
19 
22 
29 
43 
57 
Hours 
 
 
0 
4 
6 
8 
12 
24 
48 
72 
96 
 
 
 
 
 
 
 
 
 
Vital signsi 
X 
X 
Xi 
Xi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
X 
Body weight and height 
(height once at Screening) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
 
 
X 
 
 
 
 
 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serologyj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology (including 
coagulation) 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
X 
 
 
 
 
 
 
X 
Clinical chemistry 
X 
X 
 
 
X 
 
X 
X 
 
 
X 
 
X 
 
 
 
 
 
 
X 
PK samplingk 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Total IgG 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis (dipstick)l 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
X 
 
 
 
 
 
 
X 
Local tolerability of SC 
infusionm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infusion Questionnaire 
(SIAQ) 
 
 
Xn 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Injection Site Reaction 
Questionnaire (ISRQ) 
 
 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Injection site pain VAS 
 
 
Xp 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infusion site photograph 
 
 
Xq 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 1-1: 
Schedule of activities 
Assessments 
Screening 
Period 
In-Clinic Period 
Ambulatory Period 
 
SFU/WD 
Admission 
Dosing 
Weeks 
-4 to -1 
0 
1 
1 
2 
2 
3 
3 
4 
5 
7 
8 
Days 
-28 to -2 
-1a 
1 
2 
3 
4 
5b 
7 
10 
13 
16 
19 
22 
29 
43 
57 
Hours 
 
 
0 
4 
6 
8 
12 
24 
48 
72 
96 
 
 
 
 
 
 
 
 
 
Anti-rozanolixizumab 
antibodiesu 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
 
X 
Headache questionnairer 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Neurological assessments 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Serum complement (C3, C4), 
and cytokines and plasma 
complement (C3a, C5a)t  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE=adverse event; CSF=cerebrospinal fluid; CT=computed tomography; ECG=electrocardiogram; FSH=follicle-stimulating hormone; IgG=immunoglobulin G; 
IMP=investigational medicinal product; ISRQ=injection site reaction questionnaire; MP=manual push; PCR=polymerase chain reaction; 
PK=pharmacokinetic(s); SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; SC=subcutaneous(ly); SFU=Safety Follow-Up; SIAQ=self-injection 
assessment questionnaire; VAS=visual analog scale; WD=withdrawal 
a Participants may be admitted into the clinic in the evening of Day -2 for the In-Clinic Period. 
b Participants discharged during Day 5 at the discretion of principal investigator. 
c Randomization should be performed on Day 1 before dosing and after all predose assessments and procedures have been completed. 
d Rozanolixizumab will be administered as an SC infusion by syringe driver at a 
 or by MP through self-administration at a 
 
 
e This card is an emergency contact card and will be given to the participant when he/she is randomized in the clinical study (Day 1). 
f A full physical examination will be performed at the Screening Visit, Day -1, and SFU. A brief symptom-led physical examination should be performed on 
Day 5. 
g Serum pregnancy tests will be performed at the Screening Visit and on Day -1 and 29 and at the SFU Visit for all women with childbearing potential. 
h Only for postmenopausal women (for at least 1 year post-menopause before the Screening Visit) not using hormonal contraception or hormonal replacement 
therapy. 
i Vital signs will be measured predose and at 1, 2, 3, and 4 hours after the start of infusion and then prior to each PK sampling. Measurements will include blood 
pressure, pulse rate, respiratory rate, and tympanic body temperature. Vital signs and ECGs should be measured/taken before PK sampling, where applicable. 
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Single 12-lead ECGs will be taken at Screening, Admission, predose, at 4, 12, and 24 hours after the start of infusion, and once a day on Days 3, 4, and 5 until 
discharge. All ECG recordings should be taken with the study participant resting in the supine position for at least 5 minutes before the recording. 
j Serology panel: Hepatitis B surface antigen, hepatitis B core antibody (both IgG and immunoglobulin M), hepatitis C virus antibody, and human 
immunodeficiency virus 1 and 2 antibody. 
k The PK sampling time points will be: predose, immediately at the end of infusion, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after start of infusion, and on Days 7, 
10, 13, and 16. 
l Dipstick urinalysis includes: pH, protein, glucose, ketone, urobilinogen, bilirubin, blood, nitrite, leukocytes; urine spot collections for albumin:creatinine ratio, 
total protein, albumin, creatinine, alpha-1 microglobulin, and beta-2 microglobulin; specific gravity; and microscopic examination (if blood or protein is 
abnormal). 
m Assessment of local tolerability of SC infusion (by the investigator or designee) will be completed predose, at the end of infusion, and 4, 6, 8, 12, 24, 36, 48, 
72, and 96 hours after the start of infusion. 
n The SIAQ will be completed predose and 30 minutes to 1 hour postdose by study participants (MP cohorts only). 
o The ISRQ will be completed 30 minutes to 1 hour postdose by participants (syringe driver cohorts only). 
p Injection site pain VAS will be completed by all cohorts 30 minutes to 1 hour postdose. 
q Photographs of IMP injection site to be taken predose and 30 minutes after the end of the IMP administration, and additionally upon occurrence of any 
injection site reaction. An additional photograph will be taken if an injection site reaction occurs. 
r Applicable only to participants experiencing severe and/or serious headache(s). The Headache Questionnaire will be performed daily until resolution (ie, if 
headache becomes moderate or mild, normal collection of AEs should apply). Headache Questionnaire should be assessed after Day 5 (at the investigator's 
discretion) if participants are kept longer in the unit for severe headache. 
s A neurological assessment is to be performed by the investigator or designee for those participants who experience severe and/or serious headaches with a 
frequency as clinically indicated. This assessment will include: 
 
1) General appearance, including posture, motor activity, vital signs, and meningeal signs, if indicated;  
 
2) Cranial nerves;  
 
3) Motor system, including muscle tone and power and sensory system – light touch;  
 
4) Reflexes, including deep tendon reflexes;  
 
5) Coordination, gait (if possible);  
 
6) Fundoscopy.  
The neurological assessment may be performed after Day 5 (to the investigator's discretion) if headache continues. The neurological assessment may be 
repeated if headache continues and it is clinically indicated and at the discretion of the investigator. In study participants who report severe headache, other 
diagnostic procedures including a CT scan (if indicated, and at the discretion of the investigator) and lumbar puncture for CSF collection (if clinically indicated, 
and at the discretion of the investigator) should be performed (see Section 8.3.7.1.3 and Section 8.3.7.1.4, respectively). 
t Complement and cytokine sampling taken predose for all participants and at 4 and 8 hours post event only if an infusion reaction or AE of special monitoring is 
observed. Backup samples could be stored for later biomarker analyses (up to 20 years). 
u Anti-rozanolixizumab antibodies will be assessed predose and on Days 10, 16, 22, and 57. 
 
 
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In addition to those detailed in Table 1-1, the assessments in Table 1-2 may be required in case 
of infusion reactions or adverse events (AEs) of special monitoring (severe headache, severe 
gastrointestinal disorders [eg, diarrhea, abdominal pain, vomiting]). Note that additional vital 
sign measurements may be taken based on the timing of the assessments. 
Table 1-2: 
Additional study assessments 
Assessment 
When applicable 
For study participants who experience infusion reactions (excluding local injection site reactions): 
Complement and 
cytokines 
In study participants who experience an infusion reaction within the first 4 hours after 
dosing, a sample should be taken at 4 and 8 hours post event. Additionally, sampling 
is taken in case of a suspected hypersensitivity event or any clinical indication of an 
unexpected immune response. 
For study participants who experience an AE of special monitoring, including severe headache, 
moderate to severe diarrhea, moderate to severe abdominal pain, or moderate to severe vomiting: 
If the AE is initially reported during a telephone call, the study participant should be reviewed at the study 
site as soon as is practically possible for further investigation. 
Complement and 
cytokines/Explor
atory biomarkers 
In study participants who experience an AE of special monitoring (as defined in 
Section 8.3.6) within the first 4 hours after dosing, a sample should be taken at 4 and 
8 hours post event. 
For study participants who experience severe and/or serious headache, the following should be 
conducted: 
Headache 
Questionnaire 
In study participants who report severe and/or serious headache, this assessment 
should be performed daily until resolution (ie, if headache becomes moderate or mild, 
normal collection of AEs should apply) (see Section 8.3.7.1). The Headache 
Questionnaire may be repeated if clinically indicated and at the discretion of the 
investigator. 
Full neurological 
examination 
In study participants who report severe and/or serious headache, a full neurological 
examination (including fundoscopy) should be performed (see Section 8.3.7.1.2). This 
assessment should include general appearance (including posture, motor activity, vital 
signs, and meningeal signs, if indicated), cranial nerves, motor system (including 
muscle tone/power and sensory system), reflexes (including deep tendon reflexes), 
coordination (gait, if possible), and fundoscopy. The neurological assessment may be 
repeated if headache continues and it is clinically indicated and at the discretion of the 
investigator. 
CT scan and 
lumbar puncture 
for CSF 
collection 
In study participants who report severe and/or serious headache, other diagnostic 
procedures including a CT scan (if indicated, and at the discretion of the investigator) 
and lumbar puncture for CSF collection (if clinically indicated, and at the discretion of 
the investigator) should be performed (see Section 8.3.7.1.3 and Section 8.3.7.1.4, 
respectively). 
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Table 1-2: 
Additional study assessments 
Assessment 
When applicable 
For study participants who experience moderate or severe diarrhea, stool should be collected: 
Stool sample 
assessment 
In study participants who report moderate or severe diarrhea, stool collection and 
analysis should be performed (1 sample per episode of diarrhea). The frequency of 
stool sampling should be as clinically indicated in the opinion of the investigator. 
Analysis of stool samples will be performed locally (see Section 8.3.7.2.1). 
AE=adverse event; CSF=cerebrospinal fluid; CT=computed tomography 
2 
INTRODUCTION 
Rozanolixizumab is a humanized IgG4 monoclonal antibody that is being developed as an 
inhibitor of the activity of the neonatal Fc receptor (FcRn) for IgG. 
By blocking the activity 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. 
Multiple 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). The FcRn 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. Therefore, it is 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 myasthenia gravis (MG), pemphigus vulgaris, immune 
thrombocytopenia (ITP), Goodpasture’s syndrome, neuromyelitis optica, Guillain-Barré 
Syndrome, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). 
As individual disease entities, IgG autoantibody-mediated conditions are relatively rare. 
Treatment of these disorders remains a difficult clinical problem, with many of these conditions 
requiring the long-term use of corticosteroids alone or combined with cytotoxic agents. These 
therapeutic approaches are not effective in all patients and conditions and have broad 
immunosuppressive effects, which cause considerable toxicity and treatment-related morbidity. 
Treatments aimed at reducing the quantity of circulating IgG autoantibodies, including 
plasmapheresis, immunoadsorption, or high-dose intravenous immunoglobulin, are being used 
for primary and secondary therapy of autoimmune disease, particularly where 
corticosteroid-based immune suppression is not or no longer effective (eg, ITP, MG, 
Guillain-Barré Syndrome, pemphigus vulgaris). 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. 
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Therefore, specific 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 latest version 
of the Investigator’s Brochure (IB). 
For chronic diseases requiring long-term or life-long therapies, alternate modes of subcutaneous 
(SC) dosing broaden patient options for ease of use and flexibility in how they conduct their drug 
self-administration. The manual push (MP) technique is a well-established mode of 
self-administration of SC IgG, which offers the advantages of independence from a syringe 
driver, reduced infusion times, and reduced material costs. The current study aims to generate 
and characterize the safety, tolerability, PK, and PD profile for the MP technique compared with 
the currently used programmable syringe driver, for the SC dosing of rozanolixizumab in healthy 
participants. 
The MP method for SC injection of rozanolixizumab appears to be feasible because the injection 
volumes of SC rozanolixizumab administered in the clinical program are typically smaller than 
for SC IgG products (
 [HIZENTRA, GAMMANORM]), and the 
formulation viscosities are comparable (12.0mPa.s vs 14.7mPa.s for Hizentra [Maeder, 2011] 
and 8.7mPa.s for Gammanorm [Gardulf, 2016]). 
The MP technique involves the manual syringing of an investigational medicinal product (IMP) 
SC with a butterfly needle (eg, 23-25G) (Jolles, 2013). A retrospective analysis of 104 patients 
self-administering SC IgG found that for push administration using a syringe, volumes of 
 
(Shapiro, 2010). More than 80% of patients using the MP technique used only 1 infusion site per 
session, with 
 as the most common (67.3% of patients) total volume infused. In particular 
in the pediatric population, MP was preferred in the patient groups of <2 years of age and 
>10 years of age and has been shown to be a safe and convenient alternative to the pump 
infusion in children with primary immune deficiency (Shapiro, 2013). Recently, another 
comparative study switching patients from intravenous IgG infusions to SC IgG infusions 
demonstrated that the manual push method was similar in tolerability and safety profile 
(Milota et al, 2019). 
2.1 
Study rationale 
For chronic diseases requiring long-term or life-long therapies, alternate modes of SC dosing 
broaden patient options for ease of use and flexibility in how they conduct their drug self-
administration. The MP technique (also referred to as "rapid push") is a well-established mode of 
self-administration of SC IgG, which offers the advantages of independence from constant use of 
a syringe driver, reduced infusion times (median 
 for abdominal sites), 
and reduced material costs (Bienvenu et al, 2018). Currently, SC administration of 
rozanolixizumab occurs via programmable syringe drivers at a targeted 
. 
To enable an alternative to SC dosing via a syringe driver, there is considerable clinical interest 
in the possibility of employing the MP method for rozanolixizumab, particularly in light of the 
relatively low volumes involved in rozanolixizumab therapy. The current study aims to generate 
and characterize the safety, tolerability, PK, and PD profile, including between-participant 
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variability, for the MP technique compared with the currently used programmable syringe driver, 
for the SC dosing of rozanolixizumab in healthy participants. 
2.2 
Background 
Clinical experience with rozanolixizumab is as follows: a completed first-in-human study in 
healthy participants (UP0018), a completed Phase 2 study in MG (MG0002), a completed 
Phase 2 study (TP0001) and ongoing Phase 3 studies (TP0003, TP0006, and TP0004) in primary 
ITP, a completed Phase 1 study in healthy Japanese, Chinese, and Caucasian participants 
(UP0060), ongoing Phase 3 studies in MG (MG0003, MG0004, and MG0007), and ongoing 
Phase 2 studies in CIDP (CIDP01/CIDP04). All clinical dosing of rozanolixizumab has been via 
the SC route using a syringe driver, except for the evaluation of several escalating intravenous 
doses in UP0018. 
In UP0018, a Phase 1 study in Caucasian healthy study participants, rozanolixizumab was 
tolerated with an acceptable safety profile after 
 administration of up to 
 
intravenous and 
 SC doses. The most frequently reported treatment-emergent adverse 
events (TEAEs) considered related to IMP per investigator in the rozanolixizumab total SC 
group were headache (27.8%) and diarrhea (16.7%). Consistent with rozanolixizumab's 
mechanism of action, plasma IgG concentrations in UP0018 were found to decrease in a 
dose-dependent fashion, with a maximum percentage change from Baseline of 
 
 for 
 SC, respectively. Following SC dosing in UP0018, no plasma samples 
had detectable rozanolixizumab concentrations at a dose of 
 and only 2 study participants 
had detectable concentrations at 
. The only calculable maximum and total 
rozanolixizumab exposures by the SC route were for the 
 dose (maximum plasma 
concentration [Cmax]: 12.41μg/mL and area under the concentration-time curve from 0 to time t 
[AUC(0-t)]: 643.3h*μg/mL). As no 
 dose is planned in UP0106 participants, information 
regarding redosing at the same infusion site is not necessary. 
In UP0060, 
-dose SC administration of rozanolixizumab to healthy Japanese, Chinese, and 
Caucasian study participants was generally well tolerated with an acceptable safety profile after 
 SC administration of 
 doses. Overall, patterns in the 
incidence of TEAEs observed in Japanese and Chinese study participants were generally 
comparable to those observed in Caucasian participants. In all study participants, a numerically 
higher incidence of TEAEs was reported for study participants receiving rozanolixizumab 
(38 participants [77.6%] reported 115 TEAEs) compared with placebo (10 participants [62.5%] 
reported 23 TEAEs). Among participants receiving rozanolixizumab, there was a trend towards 
increased incidence of TEAEs with higher doses (55.6%, 75.0%, and 90.0% of participants in the 
rozanolixizumab 
 dose groups, respectively). Three participants 
(6.1%) reported 4 TEAEs of special monitoring (diarrhea [2 events], abdominal pain [1 event], 
and vomiting [1 event]) in the 
 cohort, all of moderate intensity. The 
 dose was 
concluded by the investigator to be not well tolerated by 1 Caucasian volunteer who reported 
moderate headache. Dose-dependent reductions in IgG and IgG subclasses, similar to that 
observed in UP0018, were seen following administration of rozanolixizumab in all 3 ethnicities. 
Tetanus- and influenza A virus-specific IgG concentrations over time were similar to total IgG 
following the administration of rozanolixizumab, generally reaching the lowest levels around 
Day 10 and returning close to Baseline by Day 57; the geometric mean concentrations for 
tetanus- and influenza A virus-specific antibodies generally remained at acceptable levels for 
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protection time in all ethnic and dose groups. Overall, the mean value of albumin remained 
within the normal range over time, and no clinically relevant changes from Baseline were 
observed. All injection site reactions observed for rozanolixizumab were self-limiting, 
short-term, and of mild intensity. 
2.3 
Benefit/risk assessment 
The healthy study participants included in this study will receive no medical benefit from 
participation. The risks from taking part in the study will be minimized through the selection of 
appropriate dose levels, selection of appropriate study participants defined by the 
inclusion/exclusion criteria, and safety monitoring. In UP0106, safety and tolerability of 
rozanolixizumab will be monitored through the use of sentinel pair dosing (Section 4.1 and 
Section 4.2), and predefined stopping rules will apply to all cohorts (see Section 6.7). Safety will 
be reviewed by a Safety Monitoring Committee (SMC) (Section 9.7). In addition, the Rapid 
Alert process will be in place throughout the study to ensure that exposure to the study 
medication is stopped if a reported event meets the stopping criteria (see Appendix 8 
[Section 10.8]). 
To date, human clinical data available for rozanolixizumab are derived from completed Phase 1 
studies (UP0018 and UP0060) in healthy study participants and completed Phase 2 studies in 
study participants with primary ITP (TP0001) and generalized MG (MG0002). Based on other 
observations from the current nonclinical and clinical studies with rozanolixizumab and clinical 
studies with other IgG antibodies in humans, the potential adverse effects that may be anticipated 
include gastrointestinal disturbances, headaches, infusion and hypersensitivity reactions, local 
tolerability and injection site reactions, and effects on vaccination response. 
Clinical development for rozanolixizumab is proceeding with dosing via the SC route of 
administration only. The Reference Safety Information provided in the current IB is therefore 
based on the safety experience with SC dosing and is the Reference Safety Information for all 
ongoing and planned clinical studies with rozanolixizumab. It will be used to perform the event 
expectedness assessments for expedited reporting and annual safety reporting. 
Vaccinations, including coronavirus disease-19 (COVID-19) vaccination, are not allowed during 
the study (Section 6.5.2). Restrictions on use of live vaccines have been identified in the 
exclusion criterion #29. If vaccination with non-live vaccines (including current available 
COVID-19 vaccines) is considered necessary, the degree of protection afforded by vaccination 
under treatment may be compromised during and after treatment with rozanolixizumab.  
Based on its mechanism of action, rozanolixizumab will reduce total IgG levels including 
vaccine-specific IgG. However, it is unlikely that the immune response to the vaccine will be 
compromised by FcRn inhibition, particularly after administration of a 
dose of 
rozanolixizumab. 
In order to keep potential confounding of safety variables to a minimum and to allow 
differentiation of safety profiles of the IMP and COVID-19 vaccine, the Screening Visit should 
not be scheduled before at least 2 weeks after the COVID-19 vaccination (Section 8.2.12). 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of rozanolixizumab may be found in the IB. The current IB 
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reflects the safety profile of SC rozanolixizumab as it is known and may change with the 
accumulation of additional data. 
3 
OBJECTIVES AND ENDPOINTS 
The objectives and corresponding endpoints for this study are presented in Table 3-1. 
Table 3-1: 
Study objectives and endpoints 
Objectives 
Endpoints/Estimands 
Primary 
• To evaluate the safety and tolerability of a 
 SC dose of rozanolixizumab 
administered to healthy participants by 
MP vs syringe driver 
• Incidence of TEAEs 
Secondary 
• To assess the PK and PD of a 
SC 
dose of rozanolixizumab administered by 
MP vs syringe driver 
PK endpoints: 
• Cmax, tmax, AUC(0-t) 
PD endpoints: 
• Baseline-corrected area under the Total 
IgG-time curve 
• Rmin 
• tmin 
Exploratory 
• To compare the PK and PD of a 
 SC 
dose of rozanolixizumab administered by 
MP vs syringe driver 
• PK comparisons: Cmax, AUC(0-t) 
• PD comparison: Baseline-corrected Total 
IgG AUC 
• To evaluate the immunogenicity of 
rozanolixizumab following SC 
administration 
• Anti-rozanolixizumab antibody screening 
status (positive or negative screen), 
confirmatory status (positive or negative 
immunodepletion), and the titer for 
“positive immunodepletion” samples at 
each scheduled assessment during the 
In-Clinic and SFU Periods 
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Table 3-1: 
Study objectives and endpoints 
Objectives 
Endpoints/Estimands 
• To evaluate the effects of 
rozanolixizumab on the concentrations of 
IgG on tetanus, influenza A virus-specific 
IgG antibody, and COVID-19 
vaccinated/previously infected 
participants 
• Values and change from Baseline in serum 
IgG concentrations at each scheduled 
assessment during the In-Clinic and SFU 
Periods 
• Values and change from Baseline in 
tetanus, influenza A virus-specific IgG 
antibodies, and COVID-19 
vaccinated/previously infected participants 
during the In-Clinic and SFU Periods 
• To assess total volume, total time, and 
infusion rate for MP and syringe driver 
• Volume of IMP administration 
• Time from start to completion and 
resultant infusion rate of IMP 
administration 
• Time of infusion setup for both modes of 
administration 
• To assess acceptability of SC 
rozanolixizumab administration by MP vs 
syringe driver 
• Postdose infusion site pain visual analog 
scale with IMP administration 
• To assess the experience with SC 
infusions 
• Pre- and postdose SIAQ for MP 
administration 
• Postdose ISRQ for syringe driver 
administration 
Other Safety 
• To evaluate changes from Baseline in 
vital signs, 12-lead electrocardiogram, 
and laboratory measurements following 
 doses of rozanolixizumab 
administered by SC MP vs syringe driver 
in healthy study participants 
• Vital signs measurements (blood pressure, 
pulse rate, respiratory rate, and body 
temperature), 12-lead electrocardiogram, 
and local tolerability assessments at each 
scheduled assessment during the In-Clinic 
and SFU Periods 
• Changes from Baseline in clinical 
laboratory assessments will consist of 
hematology including coagulation, clinical 
chemistry, and urinalysis at each 
scheduled assessment during the In-Clinic 
and SFU Periods 
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Table 3-1: 
Study objectives and endpoints 
Objectives 
Endpoints/Estimands 
• To further evaluate the safety and 
tolerability of a 
 SC dose of 
rozanolixizumab administered to healthy 
participants by MP vs syringe driver 
• Occurrence of serious TEAEs 
• Occurrence of treatment-related TEAEs 
• Occurrence of TEAEs leading to 
withdrawal 
• Occurrence of AEs of special monitoring 
• Comparison of TEAEs for MP vs syringe 
driver 
• Serum complement (C3, C4), and 
cytokines and plasma complement 
(C3a, C5a) 
AE=adverse event; AUC=area under the concentration-time curve; AUC(0-t)=area under the concentration-time curve 
from 0 to time t; Cmax=maximum plasma concentration; COVID-19=coronavirus disease-19; 
IgG=immunoglobulin G; IMP=investigational medicinal product; MP=manual push; ISRQ=injection site reaction 
questionnaire; PD=pharmacodynamic(s); PK=pharmacokinetic(s); Rmin=maximum decrease in total plasma IgG; 
SC=subcutaneous(ly); SFU=Safety Follow-Up; SIAQ=self-injection assessment questionnaire; 
TEAE=treatment-emergent adverse event; tmax=time to maximum plasma concentration; tmin=time to minimum 
IgG level 
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4 
STUDY DESIGN 
4.1 
Overall design 
This Phase 1 study is a randomized, participant-blind, investigator-blind, placebo-controlled 
safety/tolerability, PK, and PD evaluation of a 
 rozanolixizumab SC dose administered to 
healthy participants by either a programmed syringe driver or by MP via self-administration. As 
rozanolixizumab has not been administered SC to humans by MP, this study represents a 
preliminary assessment of the MP method prior to recommendation of this administration 
technique in the clinical dosing of rozanolixizumab. 
Participants will be divided into 2 body weight categories: ≥35 to <50kg and ≥50kg. Within the 
higher body weight category, 16 participants will be randomly allocated to syringe driver or MP 
cohorts and, subsequently, to rozanolixizumab (6 participants total) or placebo (2 participants 
total) (Figure 1-1). Participants of lighter body weights between ≥35 to <50kg are being 
investigated to a) support the newly recommended rozanolixizumab dosing with a fixed dose of 
 in adults of ≥35kg to 50kg (via syringe driver administration) and (b) to assess the MP 
method for a 
 IMP volume. 
Within the lower body weight category, the allocation to either syringe driver or MP will be 
determined by order of recruitment rather than randomization. The first 8 participants will be 
allocated to the syringe driver cohort and randomly allocated to receive either rozanolixizumab 
 (6 participants total) or placebo (2 participants total). The subsequent 8 participants will 
be allocated to the MP cohort and randomly allocated to receive either rozanolixizumab 
 
(6 participants total) or placebo (2 participants total). 
The treatment groups are planned to be as follows: 
• Cohort 1 (participants with a body weight of ≥35kg to <50kg) is planned to have 
6 participants receive rozanolixizumab 
 and 2 participants receive placebo via syringe 
driver at a 
. 
• Cohort 2 (participants with a body weight of ≥35kg to <50kg) is planned to have 
6 participants receive rozanolixizumab 
 and 2 participants receive placebo via MP 
through self-administration at a 
. 
• Cohort 3 (participants with a body weight of ≥50kg) is planned to have 6 participants receive 
rozanolixizumab 
 and 2 participants receive placebo via syringe driver at a 
 
. 
• Cohort 4 (participants with a body weight of ≥50kg) is planned to have 6 participants receive 
rozanolixizumab 
 and 2 participants receive placebo via MP through 
self-administration at a 
. 
Since a 
 rozanolixizumab fixed dose has not been investigated thus far in lower weight 
(35 to 50kg) healthy participants, 2 sentinel study participants (1 active + 1 placebo) will be 
incorporated into Cohort 1 in order to collect safety and tolerability data over a 72-hour period. 
The SMC will convene to evaluate all available safety and tolerability data following completion 
of a 72-hour evaluation period and prior to staggered dosing of remaining participants in 
Cohort 1. As a further precautionary step for Cohort 1, dosing of the 6 post-sentinel participants 
will be staggered such that no more than 2 participants will be dosed in a 72-hour period with a 
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minimum of 48 hours between participants. In addition, the Rapid Alert process is in place 
throughout the study to ensure that exposure to the study medication is stopped if a reported 
event meets the stopping criteria (see Appendix 8 [Section 10.8]). Cohorts are not obliged to run 
in numerical sequence (ie, cohorts could run in parallel). 
Since MP IMP administrations in this study will likely be at higher infusion rates than the 
 SC rate undertaken in all rozanolixizumab clinical studies to date, 2 sentinel study 
participants (1 active + 1 placebo) will be incorporated into Cohorts 2 and 4. Review of 48-hour 
postdose safety data by the SMC will enable dosing of the remaining participants (see  
Section 9.7 and Appendix 8 [Section 10.8]). 
The eligibility of study participants will be determined during a Screening Period of up to 
4 weeks (Day -28 to Day -2). Once eligibility is confirmed, the study participant will be admitted 
to the site (at Day -1 or the evening of Day -2) and will enter an In-Clinic Period through Day 5. 
Each study participant will receive a 
SC dose of rozanolixizumab on Day 1 and may be 
discharged beginning at Day 5 at the discretion of the investigator. Each participant will only 
receive  IMP administration. 
Beginning at Day 6, study participants will enter the Ambulatory Period and will attend the 
clinical site for study visits through Day 57 to allow sufficient time for systemic IgG levels to 
return to Baseline and for the assessment of anti-drug antibodies (ADAs). 
The total maximum study duration per study participant is up to 12 weeks. This includes a 
4-week Screening Period, 5-day In-Clinic Period, and the Ambulatory Period from Day 7 
through Day 57. 
Photographs of the infusion site will be taken, without participant personal or facial 
identification, for all participants prior to start and 30 minutes after the end of the IMP 
administration, and additionally upon occurrence of any injection site reaction. 
4.2 
Scientific rationale for study design 
Rozanolixizumab dosing in this study is supported by the results of UP0018 and UP0060, where 
rozanolixizumab was found to be well tolerated with an acceptable safety profile (see Section 2.2 
for further information). Dosing in some of the recently initiated rozanolixizumab clinical 
development program has been changed from a body weight-tiered mg/kg to a fixed (mg) basis 
(see Section 4.3), with the intention of simplifying rozanolixizumab dosing to be more 
convenient to patients and prescribers. 
As described in Section 4.1, since a 
 rozanolixizumab dose has not been investigated in 
lower weight (35 to 50kg) healthy participants, the study will initially dose 2 sentinel study 
participants (1 active + 1 placebo) in Cohort 1 to confirm safety and tolerability over a 72-hour 
period before proceeding further. Additionally, the remaining 6 participants after the sentinels 
have been dosed in Cohort 1 will be staggered such that no more than 2 participants are dosed in 
a 72-hour period, within a minimum 48 hours between participants. 
Rozanolixizumab dose equivalents of 
 and 
 have previously been investigated in 
healthy participants in UP0018 and UP0060, with highest unit SC rozanolixizumab doses being 
 (81kg participant) in UP0018 and 
 (88.5kg participant) in UP0060. Since UP0018 
and UP0060 investigated body weight-adjusted (mg/kg), rather than fixed (mg) dosing, the 
lowest body weight participants in these previous 2 studies received SC rozanolixizumab doses 
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of 
 (60.0kg and 60.3kg participants, respectively) in UP0018 and 
 
(46.2kg participant) in UP0060. Accordingly, a 
 rozanolixizumab dose has not been 
administered to healthy participants weighing <50kg to date. The specific rozanolixizumab 
formulation being used is similar to that of the formulation used in UP0060. 
4.3 
Justification for dose 
The planned dose of rozanolixizumab for this study is 
, consistent with the primary 
recommended rozanolixizumab dose of 
 
 SC in future clinical dosing of 
rozanolixizumab in MG and ITP. Simulations from a population PK/PD analysis of clinical 
rozanolixizumab data demonstrated comparable systemic rozanolixizumab exposure and IgG 
response for a 
 fixed dose and 
 and 
 doses (both these latter doses being 
clinically effective in Phase 2 studies) for adults weighing ≥35kg. The dose of 
 is identical 
to a weight-tiered dose of 
 for participants weighing ≥70kg, a weight-tiered dose of 
 for participants weighing 50kg to <70kg, and a weight-tiered dose of 
 for 
participants weighing 35kg to <50kg. A 
 dose is also being assessed in low body weight 
participants to support future rozanolixizumab pediatric development programs. 
4.4 
End of study definition 
A participant is considered to have completed the study if he/she has completed all phases of the 
study including the Safety Follow-Up Visit (Day 57). 
The end of the study is defined as the date of the last visit (the Safety Follow-Up Visit, Day 57) 
of the last study participant in the clinical study. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion criteria 
Study participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Study participant must be 18 to 65 years of age, inclusive, at the time of signing the informed 
consent. 
Type of participant 
2. Study participants who are overtly healthy in the opinion of the investigator as determined by 
medical evaluation including medical history, a general clinical examination, including 
physical examination and laboratory tests, and cardiac monitoring. 
3. Study participant must be considered reliable and capable of adhering to the protocol, 
according to the judgment of the investigator, and are able to communicate satisfactorily with 
the investigator and comply with all clinical study requirements. 
4. Study participant has blood pressure (BP) and pulse within normal range in a supine position 
after 5 minutes of rest (systolic BP: 90 to 140mmHg, diastolic BP: 50 to 90mmHg, pulse: 
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40 to 90bpm). If the study participant has results outside the stated range, repeat 
measurement may be allowed once at the discretion of the investigator. 
5. Study participant has clinical laboratory test results within the reference ranges of the testing 
laboratory or not clinically significant if outside the specified ranges, in the opinion of the 
investigator. If the study participant has results outside the stated range, repeat measurement 
may be allowed once at the discretion of the investigator. 
6. Study participant has a body temperature between 35.0°C and 37.5°C, inclusive. 
7. Study participant’s electrocardiogram (ECG) is considered “normal” or “abnormal but 
clinically nonsignificant” (as interpreted by the investigator). If the study participant has test 
results outside the specific range that are deemed potentially clinically significant, repeat of 
the investigation may be allowed once at the discretion of the investigator. 
Sex 
8.  Study participants may be male or female: 
(a) A male participant must agree to use contraception as detailed in Appendix 4 
(Section 10.4) for at least 90 days after the end of the study and refrain from donating 
sperm up to 3 months after the end of the study. 
(b) A female participant is eligible to participate if she is not pregnant (see Appendix 4 
Section 10.4), not breastfeeding, and at least 1 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) for at least 90 days after the final IMP dose. 
Weight 
9. Participant has a body mass index of 18 to 32kg/m2, with a minimum body weight of 35kg. 
Informed consent 
10. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1), which 
includes compliance with the requirements and restrictions listed in the informed consent 
form (ICF) and this protocol. 
5.2 
Exclusion criteria 
Study participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
1. History or presence of/significant history of or current cardiovascular, respiratory, hepatic, 
renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of 
significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk 
when taking the study intervention; or interfering with the interpretation of data. Study 
participant has active neoplastic disease or history of neoplastic disease within the previous 
5 years of entry in the clinical study (except for basal or squamous cell carcinoma of the skin 
or carcinoma in situ that has been definitively treated with standard of care approaches). 
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Study participant has a history of a major organ transplant or hematopoietic stem cell/marrow 
transplant. 
2. Any medical (acute or chronic illness) or psychiatric condition that, in the opinion of the 
investigator, could harm the study participant or would compromise the study participant’s 
ability to participate in this study. 
3. Abnormal BP, as determined by the investigator. 
4. Symptomatic herpes zoster within 3 months prior to Screening. 
5. Allergies to humanized monoclonal antibodies. 
6. Female who is pregnant or lactating. 
7. Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, 
or severe posttreatment hypersensitivity reactions (including, but not limited to, erythema 
multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, and 
exfoliative dermatitis). 
8. Participant has a known hypersensitivity to any components of the study medication or to any 
components of the licensed device. 
9. Evidence of active or latent tuberculosis (TB) as documented by medical history and 
examination, TB testing via a positive (not indeterminate) QuantiFERON TB Gold test, and 
responses to the TB Signs and Symptoms Questionnaire. 
10. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the 
exception of Gilbert's syndrome or asymptomatic gallstones). 
For randomized participants with a Baseline result greater than the upper limit of normal 
(ULN) for total bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful 
elevation must be understood and recorded in the electronic Case Report form (eCRF). 
11. Bilirubin >1.0×ULN (isolated bilirubin <1.5×ULN is acceptable if bilirubin is fractionated 
and direct bilirubin <35%). Tests that result above the exclusion limit may be repeated once 
for confirmation. 
12. Alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase 
(ALP) >1.0×ULN. Tests that result in ALT, AST, or ALP up to 25% above the exclusion 
limit may be repeated once for confirmation. This includes rescreening. If the repeat values 
are below the ULN, the study participant will not be considered to have met the exclusion 
criteria. 
13. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or 
squamous epithelial carcinomas of the skin that have been resected with no evidence of 
metastatic disease for 3 years. 
14. Breast cancer within the past 10 years. 
15. Absolute neutrophil count <1.5×109/L and/or lymphocyte count <1.0×109/L. 
16. Corrected serum calcium of >11.5mg/dL (>2.9mmol/L) or <8.0mg/dL (<2.0mmol/L). 
17. Predicted inability to comply with being free of caffeine and ethanol from 72 hours prior to 
clinic admission and during the In-Clinic Period of the study. 
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18. Known hypersensitivity to oral paracetamol (acetaminophen). 
19. History of known inflammatory bowel disease, active diverticular disease, or a history of 
confirmed duodenal, gastric, or esophageal ulceration in the previous 6 months. 
20. History of hyperprolinemia, since L-proline is a constituent of rozanolixizumab. 
21. Twelve-lead ECG with abnormalities considered to be clinically significant upon medical 
review: male study participants with QT interval corrected for heart rate using Fridericia’s 
formula (QTcF) >450msec and female study participants with QTcF >470msec, left bundle 
branch block, or evidence of myocardial ischemia. 
22. Renal impairment, defined as a creatinine concentration in serum of ≥1.4mg/dL 
(≥123μmol/L) for female participants and ≥1.5mg/dL (≥132μmol/L) for male participants. 
23. Known viral hepatitis (B and C) (positive serology test for hepatitis B surface antigen, 
hepatitis B core antibodies [both IgG and immunoglobulin M], hepatitis C virus antibodies) 
or human immunodeficiency virus 1/2 antibodies or has a past medical history or family 
history of primary immunodeficiency or antibodies to human immunodeficiency virus type 1 
and/or type 2 at Screening. 
24. Participant has a positive test result for severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) in reverse transcriptase-polymerase chain reaction on admission to the unit. 
25. Participant has clinical signs and symptoms consistent with SARS-CoV-2 (eg, fever, dry 
cough, dyspnea, sore throat, fatigue) or confirmed infection by appropriate laboratory test 
within the previous 14 days prior to Screening or on admission. 
26. Participant has active infection or is symptomatic with SARS-CoV-2 or is currently in 
quarantine (has been in contact with a SARS-CoV-2 positive individual in the last 14 days). 
27. Participant has had a severe course of SARS-CoV-2 (eg, requiring extracorporeal membrane 
oxygenation, mechanical ventilation, or hospitalization). 
Prior/concurrent therapy 
28. Past or intended use of over-the-counter or prescription medication (including herbal 
medications) within 14 days prior to dosing until Day 57 (specific medications listed in 
Section 6.5.1 are allowed). 
29. Live vaccine(s) within 8 weeks prior to Screening or plans to receive such vaccines during 
the study or is within a dosing cycle to receive a second dose of a coronavirus disease-19 
(COVID-19) vaccine. 
30. Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) 
within 3 months or 5 half-lives (whichever is longer) prior to dosing. 
Prior/concurrent clinical study experience 
31. Exposure to more than 3 new chemical entities within 12 months prior to dosing. 
32. Has previously been assigned to treatment in a clinical study of rozanolixizumab. 
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33. Participated in another study of an IMP (or a medical device) within the previous 90 days or 
5 half-lives prior to Day -1 (whichever is longer) or is currently participating in another study 
of an IMP (or a medical device). 
Diagnostic assessments 
34. Presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to 
dosing. 
35. Positive hepatitis C antibody test result at Screening or within 3 months prior to starting 
study intervention. NOTE: Participants with positive Hepatitis C antibody due to prior 
resolved disease can be enrolled if a confirmatory negative hepatitis C ribonucleic acid test is 
obtained. 
36. Positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of 
study medication. NOTE: Test is optional and participants with negative Hepatitis C 
antibody test are not required to also undergo Hepatitis C RNA testing. 
37. Presence of the hepatitis B core antibody (HBcAb) even if HBsAg is negative. 
38. Immunoglobulin G <7g/L or >16g/L at the Screening Visit. 
39. Positive pre-study drug/alcohol screen. 
Other exclusions 
40. Participant is splenectomized or has had an active clinically significant infection within the 
last 6 weeks. 
41. Donated or lost >500mL of blood or blood products in the 3 months preceding the start of 
dosing or plans to donate blood during the clinical study. 
42. Employee or direct relative of an employee of the contract research organization (CRO) or 
UCB. 
43. History of alcohol and/or drug abuse up to 12 months before Screening. Alcohol abuse is 
defined as follows: study participant has an alcohol consumption of more than 21 units for 
males and 14 units for females per week (1 unit of alcohol is equivalent to 10mL ethanol; for 
example, 330mL of 5% alcohol by volume beer=1.7 units; 125mL of 12% wine=1.5 units; 
50mL of spirits=2 units). 
44. Smoked on average >5 cigarettes/day (or equivalent) during the last 3 months and is not able 
to stop smoking during the In-Clinic Period. 
45. Excessive consumption of beverages or food containing xanthine bases (including 
caffeinated drinks, coffee, chocolate, etc.), equating to >400mg caffeine per day. 
5.3 
Lifestyle restrictions 
5.3.1 
Meals and dietary restrictions 
None. 
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5.3.2 
Caffeine, alcohol, and tobacco 
Participants will abstain from alcohol from the start of dosing until after collection of the final 
PK and/or PD sample. Study participants who drink alcohol will be instructed that alcohol will 
not be permitted while they are in the clinic. Study participants who use tobacco products will be 
instructed that use of nicotine-containing products (including nicotine patches) will not be 
permitted while they are in the clinic. Caffeine and alcohol use are prohibited for 72 hours prior 
to clinic admission (Day -1). 
5.3.3 
Activity 
Study participants will abstain from strenuous exercise for 48 hours before each blood collection 
for clinical laboratory tests. Study participants may participate in light recreational activities 
during the study. 
5.4 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered into the study. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants to meet the Consolidated Standards 
of Reporting Trials (CONSORT) publishing requirements and to respond to queries from 
regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE). 
Study participants may be rescreened once under conditions such as the following: 
• Study participant falls outside the Screening Period 
• If a study participant does not meet the inclusion criteria at Screening or on Day -1 due to an 
out-of-range laboratory result or a minor illness, he/she can be rescreened once at the 
discretion of the investigator. Provided all inclusion criteria are met at the second Screening, 
the study participant can be included. The repeat visit should be planned within the time 
frame of 28 days between the initial screening day and Day 1. In case study participants 
missed the 28 days window, the full screening assessments should be repeated. 
Study participants may be included if the repeat values for the laboratory screening criteria are 
within normal ranges and/or if repeat values show normalization of the out-of-range safety 
laboratory values, and/or after the study participant makes a complete recovery from the mild or 
moderate illness and if all other screening criteria are met. 
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes rescreening. 
6 
STUDY TREATMENTS 
Study treatment is defined as any investigational treatment(s), marketed product(s), or placebo or 
medical devices intended to be administered to a study participant according to the study 
protocol. 
6.1 
Treatments administered 
 
 
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Study treatment details are presented in Table 6-1. 
Table 6-1: 
Study treatments 
Study 
Treatment 
Name: 
Rozanolixizumab 
Placebo 
Syringe Driver 
Manual Push 
Syringe Driver 
Manual Push 
Dosage 
formulation: 
Solution for injection 
Solution for injection 
Unit dose 
strength: 
 
Not applicable 
Dose level 
 (MP or Syringe 
Driver)  
Not applicable 
Volume 
 
 
 
 
Route of 
Administration  
Subcutaneous infusion 
Subcutaneous infusion 
Use 
Investigational 
Placebo 
Infusion site: 
Abdomen 
Abdomen 
Infusion rate: 
 
 
Unspecified 
(individually 
variable) 
 
 
Unspecified 
(individually 
variable) 
Expected 
Duration of 
infusion: 
 
Unspecified 
(individually 
variable) 
 
Unspecified 
(individually 
variable) 
MP=manual push 
6.1.1 
Administration methods 
For details, please refer to the IMP handling manual. 
6.2 
Preparation, handling, storage, and accountability requirements 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study medication received and any discrepancies are reported 
and resolved before use of the study medication. 
Only participants enrolled in the study may receive study medication and only authorized site 
staff may supply or administer study medication. All study medication must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
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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 study medication accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
In case an out-of-range temperature is noted for longer than 15 minutes, it must be immediately 
reported as per instructions contained in the IMP Handling Manual. 
Further guidance and information for the final disposition of unused study medication are 
provided in the IMP Handling Manual. 
6.2.1 
Drug accountability 
The Drug Accountability form will be used to record study medication dispensing and return 
information on a by-participant basis and will serve as source documentation during the course 
of the study. Details of any study medication lost, damaged (due to breakage or wastage), not 
used, partially used, disposed of at the study site, or returned to the sponsor or designee must also 
be recorded on the appropriate forms. All supplies and pharmacy documentation must be made 
available throughout the study for UCB (or designee) to review. 
The investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of study medication until locally destroyed. 
The investigator may assign some of the investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The investigator must ensure that the study medication is used only in accordance with the 
protocol. 
6.3 
Measures to minimize bias: randomization and blinding 
A CRO (ie, ICON) randomization biostatistician will create the program to generate the 
randomization list and code break envelopes. The randomization biostatistician will be 
independent of the study. A dummy randomization list will be prepared by the randomization 
biostatistician following the documented and approved design in the randomization plan. The 
dummy randomization list will be reviewed and approved by the Clinical Study Biostatistician to 
ensure that the code meets the study requirements. 
After finalization of the dummy code, the randomization program will be run with a different 
seed number to create the final randomization list. The generation of the randomization list will 
occur in a secure environment. The final randomization list will be released to the appropriate 
unblinded contacts stated in the randomization plan. Electronic files will be password protected, 
and instructions will be supplied on how to obtain the password. 
The final randomization list will be retained by ICON in a secure location until the end of the 
study (ie, until after database lock). 
All study participants and investigational site staff involved in the study will be blinded to the 
IMP assignment throughout the study, with the exception of unblinded site pharmacy staff 
members involved in IMP preparation, dispensing, and dosing staff. 
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Copies of the randomization lists will be sent before the start of the study in a secure fashion 
directly from the contracted CRO to the following: 
• Sponsor Patient Safety staff for SAE reporting 
• Bioanalytical staff (to identify samples to be measured) 
• Unblinded member of pharmacy involved in IMP preparation and dispensing 
• Independent Biostatistician/Statistical Programmer 
 
 
 
No stratification factors will be used in the randomization process. 
At the Screening Visit, each study participant will be assigned a unique 5-digit participant 
number (randomization number) from a range of numbers supplied by Global Biometry 
Standards. 
Once the investigator determines that the study participant is eligible for the study, and before 
IMP administration, a central person in charge of issuing the randomization numbers will 
manually allocate the next randomization number on the list to the study participant. Each 
specific randomization number will be linked to the treatment regimen on the randomization 
schedule, which will be dispensed by the 
. The randomization numbers 
will also be recorded in the eCRF. 
6.3.1 
Procedures for maintaining and breaking the treatment blind 
6.3.1.1 
Maintenance of study treatment blind 
All study participant treatment details (cohort and treatment) will be allocated and maintained 
with randomization lists and emergency envelopes (or equivalent). 
6.3.1.2 
Breaking the treatment blind in an emergency situation 
In the event of an emergency, it will be possible to determine to which treatment arm and dose 
the study participant has been allocated using emergency envelopes (or equivalent) which should 
be stored in a secure area and can be accessed immediately by investigators. The responsibility to 
break the treatment code resides solely with the study investigators. 
An emergency envelope (or equivalent) containing the treatment allocation will be printed for 
each study participant and must not be broken, except for emergency situations. In case of a 
medical emergency with a study participant that is managed at an external medical facility, 
unblinding of the study treatment may also be requested, if considered medically appropriate. 
Study participant unblinding from an external medical facility can be requested using the contact 
details provided on the Subject Identification Card (ie, via a phone call to the Principal 
investigator, Study Physician or the Study Unit operating 24/7). 
The Clinical Project Manager must be informed immediately when a code is broken. Any 
unblinding of the IMP performed by the investigator must be recorded in the source documents 
and on the Study Termination eCRF page. 
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6.4 
Treatment compliance 
Designated site personnel will ensure treatment compliance by overseeing SC infusion of the 
IMP by the participant. Drug accountability must be recorded on the Drug Accountability form. 
Any incomplete administration of IMP will require documentation of how much was infused 
(including start and stop times). 
6.5 
Concomitant medication(s)/treatment(s) 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
The following concomitant medications are permitted during the study: 
• With approval from the investigator, paracetamol is permitted for the treatment of mild 
symptoms (eg, headache or pain), given at most 
, not exceeding 2g/day, 
and with a total of no more than 10g per 
. 
• Hormonal contraceptives, implants, patches, intrauterine hormone-releasing system, or 
intrauterine devices delivering progesterone or postmenopausal hormonal replacement 
therapy (HRT) are allowed in female participants. 
6.5.2 
Prohibited concomitant treatments (medications and therapies) 
With the exception of vitamins and the permitted concomitant treatments noted in Section 6.5.1, 
all prescription medication (including herbal medications) or over-the-counter medicines are 
prohibited from 14 days prior to dosing until follow-up (Day 57), unless required to treat an AE, 
including pretreatment. Vaccinations are not allowed during the study. 
6.5.3 
Rescue medication 
In the case of prolonged hypogammaglobulinemia, the study participant will be considered for 
treatment with prophylactic antimicrobial therapy and, where appropriate, a commercially 
available intravenous immunoglobulin. Study participants will be followed up until 
immunoglobulin levels return to within the normal range. The date and time of rescue 
medication administration as well as the name and dosage regimen of the rescue medication must 
be recorded. 
6.6 
Dose modification 
No dose modifications are allowed during the study for an individual study participant. 
6.7 
Criteria for study hold or dosing stoppage 
A rapid response procedure (Rapid Alert) for communicating serious and/or severe AEs or any 
other safety findings as described below will be operational during the study. A description of 
Rapid Alert procedures and how they may be used to facilitate prompt decision making 
regarding stopping exposure to study medication/procedures is provided in Appendix 8 
(Section 10.8). The Rapid Alert Process should occur for any SAE or any severe AEs, regardless 
of relatedness to IMP that occurs during the study period. Detailed procedures for reporting 
SAEs and other safety events that may meet study hold criteria are provided in Appendix 3 
(Section 10.3) and Appendix 8 (Section 10.8). 
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6.7.1 
Stopping rules for all cohorts 
If any of the following stopping criteria are met in any of the study cohorts, further dosing will 
be placed on hold: 
• One study participant in the cohort has an SAE considered related to the IMP as judged by 
the investigator. 
• One study participant in the cohort has anaphylaxis considered related to the IMP as judged 
by the investigator (Appendix 12 [Section 10.12]). 
• More than one study participant within the same cohort has a severe nonserious AE 
considered related to the IMP as judged by the investigator. 
If any of the stopping criteria has been met, further dosing will be suspended in all cohorts until 
further information is collected to assess the relationship with IMP. If additional information 
shows there is no relationship with IMP (eg, study participant was on placebo after unblinding), 
dosing can continue as planned. If it is deemed appropriate to restart dosing, a request to restart 
dosing with pertinent data will then be submitted as a request for a substantial amendment. 
All safety and tolerability data (including serious and nonserious AEs) will be reviewed on a 
rolling basis by the investigator and sponsor’s Study and Safety Physician (or designee). Safety 
evaluation of all available information across all cohorts will be completed by the SMC, 
including all serious AEs considered related to the IMP. In case of a safety signal, the SMC can 
recommend at any time to hold further dosing in a cohort. Restart of dosing within a cohort can 
be decided by the SMC if, after proper investigation, the safety signal is deemed to be not 
clinically relevant and when the below stopping criteria are not met. 
Following case review to confirm causality and seriousness and/or severity of reported events, 
UCB will halt further dosing if during the study there is an SAE or 2 severe or clinically 
significant AEs considered to be at least possibly related to the IMP. A severe AE is defined as a 
Common Terminology Criteria for Adverse Events grade ≥3. If following an internal safety 
review, it is appropriate to restart the study, a substantial amendment will be submitted to the 
regulatory authority and independent ethics committee (IEC). The study will not restart until the 
amendment has been approved by the regulatory authority and IEC. 
If no further dosing is planned due to the stopping criteria described above, previously 
randomized and dosed study participants will continue the study as planned. Safety assessments 
will be performed per the protocol. Pharmacokinetic and PD assessments will be performed if 
deemed to be relevant and agreed by the investigator and sponsor without compromising the 
safety of a study participant. 
Other reasons for stopping and terminating the study will be: 
• A pattern of AEs occurs that, in the opinion of the investigator and/or SMC, contraindicates 
further dosing of enrolled/additional study participants. 
• If the sponsor or its designee judges it necessary for medical, safety, regulatory, or any other 
reasons consistent with applicable laws, regulations, and Good Clinical Practice (GCP). 
• The sponsor decides to terminate the study, and no further dosing will be scheduled. 
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6.8 
Treatment after the end of the study 
Not applicable. This is a Phase 1 study in healthy participants; therefore, no treatment will be 
provided after the end of the study. 
7 
DISCONTINUATION OF STUDY MEDICATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study medication 
Events that may lead to discontinuation of study medication are described in Section 7.1.1 
through Section 7.1.3. 
7.1.1 
Hypersensitivity stopping criteria 
During the study, study participants will receive a 
 dose of investigational medicinal 
product (IMP) administered SC via a programmed syringe driver or by MP. 
This will be performed under close and continued attention of the investigator or designee. In 
case of any signs of an infusion reaction or anaphylaxis, the infusion will be stopped 
immediately, and appropriate treatment will be initiated, as necessary, at the discretion of the 
investigator. This includes the use of antihistamines for urticaria and appropriate management in 
case of potentially life-threatening events such as anaphylaxis. Infusion may be restarted in mild 
reactions only if clinically appropriate. The study participant should be followed until resolution 
of the event. Rapid Alert procedure (Appendix 8 [Section 10.8]) should be followed, if indicated. 
See Appendix 12 (Section 10.12) and Appendix 13 (Section 10.13) for procedures to follow in 
the instance of infusion reactions and anaphylaxis, respectively. 
7.1.2 
Liver chemistry stopping criteria 
The following liver chemistry stopping criteria for discontinuation of study medication do not 
apply (Figure 7-1). See Appendix 6 (Section 10.6) for procedures to follow in the instance of 
elevated liver function tests. 
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Figure 7-1: Liver chemistry stopping algorithm 
 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; INR=international normalized ratio; SAE=serious 
adverse event; ULN=upper limit of normal 
Note: Suggested assessments and follow-up actions for potential drug-induced liver injury are provided in 
Appendix 6 (Section 10.6). 
7.1.3 
QTc stopping criteria 
A participant who meets either bulleted criterion based on the ECG reading will be withdrawn 
from the study: 
• QTcF >500msec 
• Change from Baseline: QTcF >60msec 
If a clinically significant finding is identified (including, but not limited to, changes from 
Baseline in QTcF interval 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 significant finding should be reported as an AE. 
See Table 1-1 for data to be collected at the time of treatment discontinuation and follow up and 
for any further evaluations that need to be completed. 
7.2 
Participant discontinuation/withdrawal from the study 
Participants are free to withdraw from the study at any time, without prejudice to their continued 
care. The study is designed to collect data on 24 participants that receive rozanolixizumab (6 per 
cohort). If study participants discontinue before the end of the safety evaluation period, 
replacement participants may be considered at the discretion of the sponsor, depending on how 
the discontinuation affects the study’s ability to collect sufficient data to support the study 
Continue Study Treatment 
Discontinue Study Treatment 
ALT ≥3xULN 
No
Yes
Refer to the Liver Safety Required Actions and Follow-up Assessments section in 
Appendix 6. 
Report as an SAE if possible Hy’s Law case: AST/ALT ≥3xULN and Bilirubin 
≥2xULN (>35% direct) or INR>1.5, if measured 
(Note: INR value not applicable to participants on anticoagulants) 
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objectives. For each case of participant discontinuation, the decision on whether to recruit a 
replacement and the reason behind the decision will be documented. 
If the 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 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. Participants who 
withdraw from the study will be encouraged to return to the clinic to complete the Withdrawal 
Visit (see Table 1-1). 
See Table 1-1 for data to be collected at the time of study discontinuation and follow-up and for 
any further evaluations that need to be completed. 
Participants should be withdrawn from the study if any of the following events occur: 
1. Participant develops an illness that would interfere with his/her continued participation. 
2. Participant is noncompliant with the study procedures or medications in the opinion of the 
investigator. 
3. Participant takes prohibited concomitant medications as defined in this protocol that might 
interfere with the outcome of the study or might be an increased risk to the study participant. 
4. Participant withdraws his/her consent. 
5. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test. 
6. The sponsor or a regulatory agency requests withdrawal of the participant. 
7.3 
Lost to follow-up 
A 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) to complete the final evaluation. All results 
of these evaluations and observations, together with a narrative description of the reason(s) 
for removing the participant, must be recorded in the source documents. The eCRF must 
document the primary reason for withdrawal. 
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. 
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8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in Table 1-1. 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study medication. 
Adherence to the study design requirements, including those specified in Table 1-1, is essential 
and required for study conduct. 
All Screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator will maintain a Screening log to record details of all 
participants screened and to confirm eligibility or record reasons for Screening failure, as 
applicable. 
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 Screening or Baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in Table 1-1. 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 500mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the sponsor 
and site study files. A protocol amendment will be considered as appropriate. The IEC will be 
informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICF. 
8.1 
Efficacy assessments 
As this is a Phase 1 study in healthy study participants; efficacy will not be assessed. 
8.2 
Safety assessments 
Planned time points for all safety assessments are provided in Table 1-1. The acceptable 
deviation times for study procedures will be included in a separate manual. 
8.2.1 
Physical examination 
A complete physical examination will include: general appearance; head, ears, eyes, nose and 
throat; thyroid; lymph nodes; back and neck; heart; chest; lungs; abdomen; skin; and extremities; 
and musculoskeletal and neurological systems will be assessed. 
A brief symptom-led physical examination will be carried out on Day 5. Investigators should pay 
special attention to clinical signs related to previous serious illnesses. 
Clinically relevant findings or worsening of previous findings will be recorded as AEs. 
8.2.2 
Vital signs 
Vital signs will be measured in a supine position after 5 minutes rest and will include tympanic 
body temperature, respiratory rate, systolic and diastolic BP, and pulse rate. 
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All vital signs should be taken before any blood sampling (except at the end of infusion) and 
with the study participant resting in the supine position for at least 5 minutes before the 
recording. 
Blood pressure and pulse measurements will be assessed with a completely automated device. 
Manual techniques will be used only if an automated device is not available. 
Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 pulse, 
1 respiratory rate, and 3 BP measurements (3 consecutive BP readings will be recorded at 
intervals of at least 1 minute). The average of the 3 BP readings will be recorded on the eCRF. 
8.2.3 
Electrocardiograms 
Twelve-lead ECGs will be obtained as outlined in Table 1-1 using an ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Refer to 
Section 7.1.3 for QTcF withdrawal criteria and any additional QTcF readings that may be 
necessary. 
All ECG recordings should be taken before any blood sampling (except at the end of infusion) 
and with the study participant resting in the supine position for at least 5 minutes before the 
recording. 
8.2.4 
Clinical safety laboratory assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and 
Table 1-1 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. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study until the final follow-up visit should be repeated until the values return to normal or 
Baseline or are no longer considered clinically significant by the investigator or Study Physician. 
If such values do not return to normal/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 Table 1-1. 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the eCRF. 
8.2.5 
Local tolerability 
Assessment of local tolerability of SC infusion via syringe driver and MP (by the investigator or 
designee) will be completed predose, at the end of infusion, and 4, 6, 8, 12, 24, 36, 48, 72, and 
96 hours after the start of infusion. Injection site reaction, ie, any pain, burning, erythema, 
itching, and/or swelling at the injection site, will be assessed. 
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8.2.6 
Self-injection assessment questionnaire 
The self-injection assessment questionnaire (SIAQ) measures the overall experience with SC 
self-injection and will be assessed predose and 30 minutes to 1 hour postdose by participants in 
the MP cohorts only. 
8.2.7 
Injection site reaction questionnaire 
The ISRQ will be assessed 30 minutes to 1 hour postdose by participants in the syringe driver 
cohorts only. For participants with an injection site reaction, the questionnaire will be performed 
at any time that they have an injection site reaction. 
8.2.8 
Injection site pain visual analog scale 
The injection site pain visual analog scale will be assessed 30 minutes to 1 hour postdose by 
participants in both the syringe driver and MP cohorts. 
8.2.9 
QuantiFERON Test 
A QuantiFERON-TB GOLD test will be performed at the Screening Visit to identify those 
participants who have had TB or may have active or latent TB. Results of this test will be 
reported as positive, negative, or indeterminate. Participants with a positive test result will not be 
included in the study. If the result is reported as indeterminate, then the test can be repeated once. 
If the repeat test result is reported as indeterminate, then the participant will not be included in 
the study. 
8.2.10 
Tuberculosis signs and symptoms questionnaire 
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will assist with the identification of study participants who 
may require therapy for TB. A study participant who answers “Yes” to the question “Has the 
participant been in close contact with an individual with active TB, or an individual who has 
recently been treated for TB?” at Screening is excluded. A “Yes” response to any of the other 
questions within the questionnaire at Screening should trigger further careful assessment to 
determine if study participant has latent or active TB (see Section 5.2; exclusion criterion #9). 
8.2.11 
Infusion site photographs 
Photographs of the IMP injection site are be taken prior to start and 30 minutes after the end of 
the IMP administration, and additionally upon occurrence of any injection site reaction. The 
photographs are for all participants and no facial identification will appear in the photos. 
8.2.12 
COVID-19 precautions 
This clinical study is likely to run during the ongoing COVID-19 pandemic. It will be done in 
accordance with the clinical study center COVID-19 risk mitigation policy, which documents the 
clinical study center’s COVID-19 virus testing strategy for study participants and staff, social 
distancing measures, and management of COVID-19-like symptoms. The risk to study 
participants will be re-evaluated by the Sponsor throughout the COVID-19 pandemic if deemed 
necessary by emerging events. 
Study participants who are invited to receive their COVID-19 vaccination must not schedule the 
Screening Visit for UP0106 before at least 2 weeks after having received their vaccination to not 
confound the Screening Baseline results for safety parameters with potential transient changes 
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due to the COVID-19 vaccine. This time period will also result into an approximately 4-week 
time period between the COVID-19 vaccination and IMP dosing allowing clear differentiation of 
the safety profile of the IMP and the vaccine. 
Study participants will be closely monitored for any signs and symptoms of COVID-19 (ie, 
fever, dysgeusia [taste loss/change], dysosmia [loss or distortion/change of smell], or persistent 
cough) throughout the study. If symptoms and/or clinical signs of infection are identified, the 
investigator will decide whether these findings will be handled as suspected or confirmed 
COVID-19. The use of testing for SARS-CoV-2 will be determined by reference to the 
regulatory and healthcare guidance in place locally at the time. In the case that COVID-19 is 
suspected or confirmed, the investigator will determine in discussion with the UCB Study 
Physician how soon the participant may be discharged from the clinical study center and whether 
this will be to their home or another healthcare facility. 
8.3 
AEs and SAEs 
The definitions of device-related safety events, adverse device effects (ADEs), and serious 
adverse device effects can be found in Appendix 7 (Section 10.7). 
AEs will 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 study treatment or study procedures, or that caused the 
participant to discontinue the study (see Section 7). 
8.3.1 
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 Safety Follow-
up/Withdrawal Visit at the time points specified in Table 1-1. Medical occurrences that begin 
before the start of study medication but after obtaining informed consent will be recorded on the 
Medical History/Current Medical Conditions section of the eCRF and not the AE section. 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the eCRF even if no study medication was taken 
but specific study procedures were conducted. This includes all AEs not present prior to the 
initial visit and all AEs that recurred or worsened after the initial visit. 
All SAEs will be recorded and reported to the sponsor or designee within 24 hours as indicated 
in Appendix 3 (Section 10.3) and the procedure for rapid alert will be followed as indicated in 
Appendix 8 (Section 10.8). 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 study 
medication), 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 study medication must be reported to 
UCB regardless of the time between the event and the end of the study. 
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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). 
8.3.2 
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. 
8.3.3 
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 (Section 8.3.6) 
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). 
8.3.4 
Regulatory reporting requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
medication under clinical investigation are met. 
The sponsor has a legal responsibility to notify regulatory authorities about the safety of a study 
medication under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, IEC, and 
investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
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 IEC, if appropriate according to local requirements. 
8.3.5 
Pregnancy 
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study medication and until 1 month after the end of the study for 
female participants and 3 months after the end of the study for female partners of male 
participants. 
If a pregnancy is reported, the investigator must immediately inform the sponsor 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 return for an early discontinuation visit. 
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• A Safety Follow-Up Visit should be scheduled ≤7 days after the participant has informed the 
sponsor of the pregnancy. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
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. For rozanolixizumab, the following events require 
immediate reporting (within 24 hours regardless of seriousness) to UCB: 
• Potential Hy’s Law, defined as ≥3×ULN ALT or AST with coexisting ≥2×ULN total 
bilirubin in the absence of ≥2×ULN 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. 
8.3.7 
Adverse events of special monitoring 
For rozanolixizumab, AEs of special monitoring that require immediate reporting to UCB are: 
• Severe headache 
• Severe gastrointestinal disturbances (ie, abdominal pain, diarrhea, or vomiting) 
• Opportunistic infection 
These events require immediate reporting to UCB (within 24 hours), regardless of seriousness, 
using the fax and email details for SAE reporting. 
8.3.7.1 
Severe headache 
Severe headache is defined as severe pain limiting self-care activities of daily living (ADL) or 
new/prolonged hospitalization for management of headache or life-threatening consequences 
requiring urgent medical intervention. Self-care ADLs refer to bathing, dressing and undressing, 
feeding self, using the toilet, taking medications. Treatment of headache will be provided as 
clinically indicated according to the local guidelines. 
The following safety assessments are applicable only to study participants experiencing severe 
and/or serious headache(s): the Headache Questionnaire, a neurological assessment (including 
fundoscopy), a computed tomography (CT) scan (if indicated, and at the discretion of the 
investigator), and a lumbar puncture for cerebrospinal fluid (CSF) collection (if clinically 
indicated and at the discretion of the investigator) will be performed. 
8.3.7.1.1 
Headache questionnaire 
The Headache Questionnaire is applicable only to study participants experiencing severe and/or 
serious headaches and will be performed daily until resolution (ie, if headache becomes moderate 
or mild, normal collection of AEs should apply); this assessment will be followed by a 
neurological assessment (including fundoscopy), a CT scan (if indicated, and at the discretion of 
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the investigator), and a lumbar puncture for CSF collection (if indicated, and at the discretion of 
the investigator). 
8.3.7.1.2 
Neurological assessments 
Neurological assessments will be performed only for those study participants who experience 
headaches with a frequency as clinically indicated (and at the discretion of the investigator). This 
assessment may include general appearance (including posture, motor activity, vital signs, and 
meningeal signs, if indicated), cranial nerves, motor system (including muscle tone/power and 
sensory system), reflexes (including deep tendon reflexes), coordination (gait, if possible), and 
fundoscopy. 
8.3.7.1.3 
CT scan 
For study participants experiencing severe headache(s), a CT scan may be performed if 
indicated, and at the discretion of the investigator. 
8.3.7.1.4 
CSF sampling 
For study participants experiencing severe headache(s), a lumbar puncture for CSF collection 
may be performed if clinically indicated, and at the discretion of the investigator. 
8.3.7.2 
Moderate or severe diarrhea 
Moderate or severe diarrhea is defined as an increase of ≥4 stools per day over Baseline or 
incontinence due to urgency of diarrhea or new/prolonged hospitalization for management of 
diarrhea or limiting self-care ADL or life-threatening consequences requiring urgent medical 
intervention. 
For study participants with moderate or severe diarrhea, stool samples will be collected. 
8.3.7.2.1 
Stool sampling 
Stool collection will be performed for study participants with a severe AE of gastrointestinal 
disturbance that is considered related to the IMP (1 sample per episode of diarrhea). 
8.4 
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 study medication so that investigators, clinical study participants, 
regulatory authorities, and ECs will be informed appropriately and as early as possible. 
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the Patient Safety 
representative. In addition, an SMC will be implemented to review ongoing study data as 
appropriate (see Section 10.1.5). 
As appropriate for the stage of development and accumulated experience with the study 
medication, 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. 
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8.5 
Treatment of overdose 
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the Drug Accountability module of the eCRF. Any SAE or nonserious AE associated 
with excessive dosing must be followed as any other SAE or nonserious AE. These events are 
only considered AEs or SAEs if there are associated with clinical signs and symptoms or if the 
act of taking the excess medicine itself is an AE or SAE (eg, suicide attempt). 
For this study, any dose of rozanolixizumab greater than that prescribed in the protocol will be 
considered an overdose. Overdose events are only considered AEs or SAEs if there are 
associated clinical signs and symptoms or if the act of taking the excess study medication 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 should: 
1. Inform sponsor’s Study Physician immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until study 
medication can no longer be detected systemically (at least 56 days from the last dose), as 
appropriate. 
3. Obtain a plasma sample for PK analysis within 10 days from the date of the last dose of study 
medication if requested by the Study Physician (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. 
8.6 
Pharmacokinetics 
Planned time points for all PK assessments are provided in Table 1-1. 
Samples will be collected for measurement of plasma concentrations of rozanolixizumab as 
specified in Table 1-1. Blood samples may be collected at additional time points during the study 
if warranted and agreed upon between the investigator and the sponsor. Instructions pertaining to 
sample collection, processing, storage, labeling, and shipping are provided in the laboratory 
manual. The actual date and time (24-hour clock time) of each sample will be recorded. 
Samples collected for analyses of rozanolixizumab plasma concentration may also be used to 
evaluate safety or efficacy aspects related to concerns arising during or after the study. 
Drug concentration information that would unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded. 
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the sponsor 
and site study files, but will not constitute a protocol amendment. The IEC will be informed of 
any safety issues that require alteration of the safety monitoring scheme or amendment of the 
ICF. 
8.7 
Genetics 
Not applicable; genetics are not evaluated in this study. 
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8.8 
Pharmacodynamics 
Venous blood samples will be collected at timepoints specified Table 1-1 for the measurement of 
Total IgG. Instructions pertaining to sample collection, processing, storage, labeling, and 
shipping are provided in the laboratory manual. 
8.9 
Biomarkers 
Details on processes for collection and shipment and destruction of these samples can be found 
in the Laboratory Manual. 
Serum complement (C3, C4), cytokines, and plasma complement (C3a, C5a) are to be taken 
predose for all participants and at 4 and 8 hours post event, only if an infusion reaction or AE of 
special monitoring is observed. 
Remaining backup samples could be stored at -80°C for up to 20 years for later exploratory 
analyses. 
Detailed information on sample analyses will be provided in a bioanalytical report. 
8.9.1 
Immunogenicity assessments 
Immunogenicity testing will occur via a tiered analysis approach consisting of a Screening, 
confirmatory, and titration assay. Anti-drug antibodies to rozanolixizumab will be evaluated in 
plasma samples collected from all study participants according to Table 1-1. 
Additionally, for study participants withdrawing from the study an unscheduled sample should 
be taken for ADA analysis upon his/her last withdrawal visit. These samples will be tested by the 
sponsor or sponsor's designee. 
Plasma samples with a "positive screen" result will enter a confirmatory ADA analysis 
whereupon addition of excess rozanolixizumab to the sample is performed in an attempt to 
immunodeplete the ADA signal. For samples with a "positive immunodepletion," an ADA titer 
will be determined. 
The detection and characterization of antibodies to rozanolixizumab, vaccinations, and previous 
SARS-CoV-2 infections will be performed using a validated assay method under the supervision 
of the sponsor. Samples for ADA analysis may be stored for a maximum of 20 years 
(or according to local regulations) following the last participant’s last visit for the study at a 
facility selected by the sponsor to enable further analysis of immune responses to 
rozanolixizumab. 
8.10 
Medical resource utilization and health economics 
Medical resource utilization and health economic parameters are not evaluated in this study. 
9 
STATISTICAL CONSIDERATIONS 
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP). Deviations in analyses from the final SAP will be documented in the 
Clinical Study Report. 
9.1 
Definition of analysis sets 
The following are the defined analysis sets: 
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• Enrolled Set: All study participants who have signed the ICF. 
• Randomized Set: All enrolled study participants who were randomized. 
• Safety Analysis Set: All randomized study participants who received IMP. Analysis of this 
set will be according to the treatment the study participants actually received and will be used 
for the demographic and safety analyses. 
• PK Per Protocol Set: All study participants that received active study medication and had at 
least 1 observable PK measurement. If a study participant in the PK Per Protocol Set is 
missing individual time points or are otherwise unobservable, they will be included in the PK 
Per Protocol Set but those time points will be omitted from the PK summaries, as 
appropriate. 
• PD Per Protocol Set: Is a subset of the Safety Analysis Set, consisting of those study 
participants who had no important protocol deviations affecting the PD variables, as 
confirmed during a pre-analysis review of the data prior to database lock. 
9.2 
General statistical considerations 
All analyses will be performed using SAS version 9.4 or later (SAS Institute, Cary, NC, USA). 
Statistical evaluation will be performed by UCB or designee and supervised by the Statistics 
Department of UCB. Analysis of PK data will be performed using Phoenix® WinNonlin® 
software. 
Data will be summarized by dose level, body weight category, treatment, and method, where 
applicable. For continuous variables, summary statistics will include number of study 
participants, treatment mean, median, standard deviation, minimum, and maximum. Categorical 
endpoints will be summarized using number of study participants, frequency, and percentages. In 
addition, all data will be listed. 
Baseline will be the last nonmissing data collected prior to the IMP administration, and 
measurement-specific Baseline values will be defined in the SAP. 
9.3 
Planned efficacy/outcome analyses 
Not applicable; efficacy is not evaluated in this study. 
9.4 
Planned safety and other analyses 
9.4.1 
Safety analyses 
All safety variables will be analyzed by descriptive methods and presented by treatment 
(rozanolixizumab or placebo), method (MP or syringe driver), body weight, and dose level. All 
IMP administration details (including date, time of infusion start and stop, and volume given) 
will be listed. Additionally, safety parameters may be summarized by weight group. Frequency 
and intensity of TEAEs will be assessed as the primary safety variable in this clinical study. 
Additional analyses are described in the SAP. 
9.4.1.1 
Adverse events 
All AEs will be coded using the Medical Dictionary for Regulatory Activities and characterized 
as pretreatment and treatment-emergent according to the intake of the IMP. A TEAE is defined 
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as any AE with a start date/time on or after the dosing of study medication until 8 weeks after 
dosing of study medication. 
Only TEAEs will be included in the summary tables and listings. 
The frequency of all TEAEs during the study period will be presented separately by system 
organ class, high level term, and preferred term. The data will be displayed as number of 
participants experiencing the TEAEs, percentage of participants, and number of TEAEs, by 
treatment, method, body weight, and dose level. 
Additional tables will summarize TEAEs leading to study medication interruption, TEAEs by 
maximum intensity, TEAEs by intensity, TEAEs by relationship to study medication, TEAEs of 
special interest, and TEAEs of special monitoring. Additional analyses are described in the SAP. 
9.4.1.2 
Clinical laboratory tests 
Laboratory variables and changes from Baseline will be summarized by descriptive statistics at 
each time point by treatment, method, body weight, and dose level. Shift tables from Baseline to 
each post-Baseline time point will be presented by treatment, method, body weight, and dose 
level. Values outside the reference range will be flagged in the listings. 
9.4.1.3 
Vital signs and electrocardiograms 
Vital sign variables (BP, pulse rate, respiratory rate, and body temperature) and changes from 
Baseline will be summarized by descriptive statistics at each time point by treatment, method, 
body weight, and dose level. 
The individual mean at each time point will be calculated as raw parameters for descriptive 
analysis. The raw parameters and change from Baseline will be summarized by descriptive 
statistics at each time point by treatment, method, body weight, and dose level. 
9.4.1.4 
Physical examinations 
Physical examination abnormalities will be listed. 
All other safety assessments (including but not limited to: local tolerability of SC infusion, 
neurological assessment, Headache Questionnaire, and CSF data) will be listed. 
9.4.2 
PK analyses 
Pharmacokinetics will be determined by non-compartmental analysis in Phoenix (Certara, USA) 
using the PK Per Protocol Set. 
For calculation of the plasma PK parameters of rozanolixizumab, the actual sampling time points 
will be used in order to evaluate the PK parameters. 
The plasma concentration-time profiles and PK parameters of rozanolixizumab will be 
summarized by method, body weight, and dose level using descriptive statistics (number of 
available observations, arithmetic mean, standard deviation, the geometric mean, the coefficient 
of variation of the geometric mean, median, minimum, and maximum). Values below the lower 
limit of quantification (LLOQ) will be reported with a clear sign indicating that they were below 
the LLOQ. Descriptive statistics of concentrations will be calculated if at least two-thirds of the 
individual data points are quantifiable (≥LLOQ). 
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Individual concentration time profiles will be displayed graphically on a linear-linear scale and 
semi-logarithmic scale. Geometric mean plasma concentrations-time curves including 95% 
confidence intervals will be displayed by method, body weight, and dose level. 
The comparability of dose-adjusted PK parameters (Cmax/D and AUC(0-t)/D) between the 
methods (MP and the syringe driver) will be assessed within an analysis of variance model with 
Method (MP vs syringe driver) as a main effect. 
9.4.3 
PD analyses 
Total IgG (observed values, change from Baseline, and percentage change from Baseline) will be 
listed and summarized for the PD Per Protocol Set. The geometric mean Total IgG concentration 
with 95% confidence interval will be displayed graphically. 
Derived parameters for the Total IgG response curve (AUC, maximum decrease in total plasma 
IgG, and time to minimum plasma concentration) will be listed and summarized for the PD Per 
Protocol Set. 
The comparability of the total IgG Baseline-corrected AUC(IgG)/D between MP and the syringe 
driver will be assessed within an analysis of covariance model analogous to the analysis of 
variance model used to evaluate the PK parameters described above. The Baseline IgG value will 
be fitted as a covariate. 
9.4.4 
Other analyses 
Plasma concentrations of anti-rozanolixizumab antibodies will be summarized by descriptive 
statistics at each time point by treatment, method, body weight, and dose level. In addition, 
anti-rozanolixizumab antibody positive study participants will be summarized in terms of 
numbers of positive study participants by ethnic group and treatment group at each time point 
and at any time postdose. 
Immunogenicity variables will be listed, plotted, and summarized. Further details will be 
provided in the SAP. 
9.5 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the PK and PD and key safety for an individual study 
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 all important deviations will be identified and 
documented before unblinding to confirm exclusion from analysis sets. 
9.6 
Handling of dropouts or missing data 
In general, there will be no imputation of missing data. Handling of missing or partial dates 
and/or times for safety assessments will be described in the SAP. 
9.7 
Planned interim analysis and data monitoring 
No formal interim analyses are planned for this study. 
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9.8 
Determination of sample size 
No formal statistical sample size calculation has been performed as this study constitutes a 
preliminary assessment of SC rozanolixizumab delivery by MP. The primary objective of the 
study is to evaluate the safety and tolerability of a 
 SC dose of rozanolixizumab 
administered to healthy participants by MP vs syringe driver. A total sample size of 
approximately 32 participants randomly assigned to study medication resulting in at least 
6 evaluable participants per cohort is considered sufficient to meet the primary objective. 
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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 IEC, as defined in local regulations, 
International Council for Harmonisation (ICH)-GCP, and in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki. 
The investigator/UCB will ensure that an appropriately constituted IEC that complies with the 
requirements of the current ICH-GCP version or applicable country-specific regulations will be 
responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the investigator/UCB will forward copies of the protocol, Informed 
Consent form, IB, investigator’s curriculum vitae (if applicable), advertisement (if applicable), 
and all other participant-related documents to be used for the study to the IEC for its review and 
approval. 
Before initiating a study, the investigator will have written and dated full approval from the 
responsible IEC for the protocol. 
The investigator will also promptly report to the 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 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 IEC as allowed. 
As part of the IEC requirements for continuing review of approved studies, the investigator will 
be responsible for submitting periodic progress reports to the IEC (based on 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 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 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 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 Informed Consent form should be signed and personally 
dated by the participant, or his/her legal representative, and by the person who conducted the 
informed consent discussion (investigator or designee). The participant or his/her legal 
representative must receive a copy of the signed and dated Informed Consent form. As part of 
the consent process, each participant must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IEC review, and regulatory inspection. 
If the Informed Consent form is amended during the study, the investigator (or the sponsor, if 
applicable) must follow all applicable regulatory requirements pertaining to the approval of the 
amended Informed Consent form by the IEC and use of the amended 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 Informed Consent 
form. 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. 
The investigator agrees that representatives of UCB, its designee, representatives of the relevant 
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 IEC members, and by inspectors from regulatory authorities. 
10.1.5 
Committees structure 
An SMC will be implemented to review ongoing available study safety data according to the 
study design outlined in Section 4.1. The composition and operational conduct of the SMC will 
be detailed in the study SMC Charter. The principal investigator will participate in the decision 
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of continuing dosing of the remaining participants on each of these cohorts based on the safety 
data obtained from the sentinel participants dosing. The SMC will review all available 
safety/tolerability data in this study (including at a minimum; safety laboratory, vital signs, ECG, 
AE, any infusion-related reactions, and hypersensitivity reactions) and PK data as necessitated 
by the SMC to make recommendations as appropriate. 
10.1.6 
Data quality assurance 
All participant data relating to the study will be recorded on printed or eCRF unless transmitted 
to the sponsor or designee electronically (eg, laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by physically or 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, 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, legible, contemporaneous, original, and 
attributable 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 must be retained by the investigator for the minimum retention period 
mandatory under the applicable local laws and regulations. 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. 
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. 
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. 
10.1.7 
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, 
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optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). 
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 sponsor 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 IEC or local 
health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further study medication development 
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 the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor 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 the table below will be performed by the local laboratory. 
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. 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
Coagulation: 
INR 
prothrombin time 
activated partial 
thromboplastin time 
fibrinogen 
WBC Count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistrya 
Blood Urea Nitrogen 
Potassium 
AST/Serum Glutamic-
Oxaloacetic Transaminase 
Total Protein 
Creatinine 
Sodium 
ALT/Serum Glutamic-
Pyruvic Transaminase 
Lipids 
Total cholesterol 
HDL cholesterol 
LDL cholesterol 
HDL/LDL ratio 
Triglycerides 
Glucose (non-fasting) 
Corrected 
calcium 
Alkaline phosphatase 
Phosphate 
Total and direct bilirubin 
Routine 
urinalysis 
• 
Specific gravity 
• 
pH, protein, glucose, ketone, urobilinogen, bilirubin, blood, nitrite, and leukocytes by 
dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
• 
albumin:creatinine ratio, total protein, albumin, creatinine, alpha-1 microglobulin, and 
beta-2 microglobulin 
Stool sampling 
volumeb 
• 
Occult blood, microscopy, culture, and lactoferin 
CSFc 
• 
Cell count, Gram staining, culture, protein, glucose, exploratory biomarkers 
Immunologyd 
• 
Complements and cytokines 
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Laboratory 
Assessments 
Parameters 
Other Screening 
Tests 
• 
Follicle-stimulating hormone (as needed in women of non-childbearing potential only) 
• 
Urine alcohol and drug screen (to include at minimum: amphetamines, barbiturates, cocaine, 
opiates, cannabinoids and benzodiazepines) 
• 
Serum human chorionic gonadotropin pregnancy test (as needed for women of childbearing 
potential) 
• 
Serology (Hepatitis B surface antigen, hepatitis B core antibody [both immunoglobulins G 
and M], hepatitis C virus antibody, and human immunodeficiency virus 1 and 2 antibody) 
• 
Tuberculosis test 
• 
Screening for influenza, tetanus, and SARS-CoV-2 vaccinations/antibodies to previous 
SARS-CoV-2-infection 
• 
The results of each test must be entered into the electronic case report form 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CSF=cerebrospinal fluid; HDL=high-density 
lipoprotein; INR=International Normalized Ratio; LDL=low-density lipoprotein; MCH=mean corpuscular 
hemoglobin; MCV=mean corpuscular volume; RBC=red blood cell; SARS-CoV-2=severe acute respiratory 
syndrome coronavirus 2; ULN=upper limit of normal; WBC=white blood cell 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Section 1.1 and Appendix 6 (Section 10.6). All events of ALT ≥3×ULN and 
bilirubin ≥2×ULN (>35% direct bilirubin) or ALT ≥3×ULN 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 (excluding studies of hepatic 
impairment or cirrhosis). 
b Only for study participants with moderate or severe diarrhea (1 sample per episode of diarrhea). 
c Only for study participants with severe headache, if clinically indicated, at the discretion of the investigator (if 
headache becomes moderate or mild, normal collection of adverse events should apply). 
d In study participants who experience an infusion reaction within the first 4 hours after dosing, a sample should be 
taken at 4 and 8 hours post event. Additionally, sampling is taken in case of a suspected hypersensitivity event or 
any clinical indication of an unexpected immune response. 
Investigators must document their review of each laboratory safety report. 
Laboratory/analyte results that could unblind the study will not be reported to investigative sites 
or other blinded personnel until the study has been unblinded. 
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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 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally 
associated with the use of study medication, whether or not considered related to the study 
medication. 
• 
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 study medication. 
 
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), 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 study medication 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 study medication or 
a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
 
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 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. 
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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. 
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 1 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. 
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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. 
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 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 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. 
 
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Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study medication 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 study medication administration will be 
considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure 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 1 of the criteria used when determining regulatory reporting 
requirements. 
 
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, or the participant is lost to follow up. This 
follow-up requirement applies to AEs, SAEs, and AEs of special interest. 
• 
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 postmortem 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. 
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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 next section). 
• 
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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10.4 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
10.4.1 
Definitions 
10.4.1.1 
Woman of childbearing potential 
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 level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or HRT. However, in the absence of 12 months of amenorrhea, a single 
follicle-stimulating hormone 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. 
10.4.2 
Contraception guidance 
10.4.2.1 
Male participants 
Male participants with female partners of childbearing potential (including partners who are 
pregnant or breastfeeding) must use contraception if any of the following criteria are met: 
• Genotoxic study medication 
• Study medication where reproductive toxicology studies have not yet been conducted 
• Study medication with demonstrated or suspected human teratogenicity/fetotoxicity at 
subtherapeutic exposure levels if relevant systemic concentrations may be achieved in 
WOCBP from exposure to seminal fluid 
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Male participants with female partners of childbearing potential are eligible to participate if they 
agree to 1 of the following (during the protocol-defined time frame in Section 5.1): 
• 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 plus partner use of a contraceptive method with a failure rate of 
<1% per year as described in the table below 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 end of the study. 
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 protocol-defined time frame. 
10.4.2.1.1 
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 10-1. 
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Table 10-1: 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 progestogen containing) hormonal contraception associated with inhibition of 
ovulationc 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 
Highly Effective Methods That Are User Independent 
• 
Implantable progestogen only hormonal contraception associated with inhibition of ovulationc 
• 
Intrauterine device 
• 
Intrauterine hormone-releasing system 
• 
Bilateral tubal occlusion 
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the partner is the sole 
male sexual partner of the women of childbearing potential and the absence of sperm has been confirmed. 
If not, an additional highly effective method of contraception should be used. 
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/intrauterine devices, principal 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 participating in clinical studies. 
c Hormonal contraception may be susceptible to interaction with the study medication, which may reduce the 
efficacy of the contraceptive method. In this case, 2 highly effective methods of contraception should be utilized 
during the treatment period and for at least 30 days after the end of the study. 
10.4.2.2 
Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test. Additionally, WOCBP with an implant or an intrauterine 
device (who may not have menstrual periods) can be included if the method of contraception 
is documented, used for more than 28 days (if no confirmed menstrual period), and they have 
a negative serum pregnancy test. 
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• Additional serum pregnancy testing should be performed on Day 29 and Day 57 and as 
required locally. 
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
• Serum pregnancy testing, with a sensitivity of 25 mIU/mL will be performed. 
10.4.2.3 
Collection of pregnancy information 
10.4.2.3.1 
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. If the study participant is later found 
to be on placebo, then pregnancy data collection can stop. 
• 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 24 hours 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. 
10.4.2.3.2 
Female participants who become pregnant 
• 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 24 hours 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 8.3.5. 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. 
• Any female participant who becomes pregnant while participating in the study will be 
withdrawn from the study. 
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10.5 
Appendix 5: Genetics 
Not applicable 
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10.6 
Appendix 6: Liver safety – suggested actions and follow-up 
assessments 
Participants with potential drug-induced liver injury must be assessed. 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 study 
medication discontinuation to complete the final evaluation. 
Study participants with potential drug-induced liver injury 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 study medication discontinuation and/or participant 
withdrawal (if applicable), must be recorded in the source documents. The eCRF must document 
the primary reason for discontinuation of study medication. 
A specific monitoring plan must be agreed between the UCB Study Physician and the 
investigator for study participants who have ALT >5 ULN. The monitoring plan should include 
any necessary follow-up assessments (until resolution of the abnormal lab values). 
Phase 1 liver chemistry stopping criteria are designed to assure participant safety and to evaluate 
liver event etiology (Table 10-2). 
Decisions concerning which assessments should be performed are to be made by the Principal 
Investigator (or delegate). A hepatologist may be consulted if deemed necessary by the 
investigator. 
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Table 10-2: Phase 1 liver chemistry stopping criteria and follow-up 
assessments 
Liver Chemistry Stopping Criteria – Liver Stopping Event 
ALT-absolute 
ALT ≥3×ULN 
If ALT ≥3×ULN AND bilirubin 2×ULN (>35% direct bilirubin) OR INR >1.5, report as 
an SAEa,b 
See additional actions and follow-up assessments listed below 
Required Actions and Follow-up Assessments 
Actions 
Follow-Up Assessments 
• 
Immediately discontinue study intervention 
• 
Report the event to UCB within 24 hours 
• 
Complete the liver event eCRF, and complete 
an SAE data collection tool if the event also 
met the criteria for an SAEb 
• 
Perform liver function follow-up assessments 
• 
Monitor the participant until liver function 
test abnormalities resolve, stabilize, or return 
to baseline (see MONITORING) 
• 
Consider the need for a toxicology screening. 
MONITORING: 
If ALT ≥3xULN AND bilirubin 2xULN or 
INR >1.5 
• 
Repeat liver function tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver function follow-up assessments 
within 24 hours. 
• 
Monitor participant twice weekly until liver 
function test abnormalities resolve, stabilize, 
or return to baseline. 
• 
A specialist or hepatology consultation is 
recommended. 
If ALT ≥3xULN AND bilirubin <2xULN and 
INR ≤1.5: 
• 
Repeat liver function tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver function follow-up assessments 
within 24 to 72 hours 
• 
Monitor participants weekly until liver 
function abnormalities resolve, stabilize, or 
return to baseline 
• 
Viral hepatitis serologyc 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the transaminases 
values show downward trend 
• 
Obtain blood sample for pharmacokinetic 
(PK) analysis within 2 days after the most 
recent dosed  
• 
Serum creatine phosphokinase and lactate 
dehydrogenase 
• 
Fractionate bilirubin, if total bilirubin 
 2xULN 
• 
Complete blood count with differential to 
assess eosinophilia 
• 
Record the appearance or worsening of 
clinical symptoms of liver injury (eg, fatigue, 
nausea, vomiting, right upper quadrant pain), 
or hypersensitivity, on the AE eCRF 
• 
Record use of concomitant medications 
(including acetaminophen, herbal remedies, 
and other over-the-counter medications) on 
the concomitant medications eCRF 
• 
Record alcohol use on the liver event alcohol 
intake eCRF 
If ALT ≥3xULN AND bilirubin 2xULN or 
INR >1.5: 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative total 
IgG or gamma globulins 
• 
Serum acetaminophen adduct high 
performance liquid chromatography assay 
(quantifies potential acetaminophen 
contribution to liver injury in participants with 
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Table 10-2: Phase 1 liver chemistry stopping criteria and follow-up 
assessments 
Liver Chemistry Stopping Criteria – Liver Stopping Event 
ALT-absolute 
ALT ≥3×ULN 
If ALT ≥3×ULN AND bilirubin 2×ULN (>35% direct bilirubin) OR INR >1.5, report as 
an SAEa,b 
See additional actions and follow-up assessments listed below 
Required Actions and Follow-up Assessments 
Actions 
Follow-Up Assessments 
definite or likely acetaminophen use in the 
preceding week [James et al, 2009]) NOTE: 
Not required in China. 
• Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver 
disease; complete liver imaging and/or 
liver biopsy eCRFs 
AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; eCRF=electronic case 
report form; HBsAg=hepatitis B surface antigen; HBcAb=hepatitis B core antibody; IgG=immunoglobulin G; 
IgM=immunoglobulin M; INR=International Normalized Ratio; PK=pharmacokinetic; RNA=ribonucleic acid; 
SAE=serious adverse event; ULN=upper limit of normal 
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention if ALT ≥3xULN. 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 hepatic 
impairment or cirrhosis). The INR measurement is not required and the stated threshold value will not apply to 
participants receiving anticoagulants. 
c Hepatitis A 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. 
d PK sample may not be required for participants known to be receiving placebo or non-comparator interventions. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior 
to the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s 
best approximation. If the date/time of the last 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 Study Reference Manual. 
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10.7 
Appendix 7: Medical device AEs, ADEs, SAEs, and device 
deficiencies: definition and procedures for recording, 
evaluating, follow-up, and reporting 
Not applicable 
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10.8 
Appendix 8: Rapid alert procedures 
The aim of the Rapid Alert process is to stop the exposure to the study medication or concerned 
study procedure as soon as possible, following a confirmed or suspected safety issue, preventing 
its reoccurrence in other study participants. Upon occurrence of an SAE and/or another safety 
event including stopping rules for all cohorts which may constitute a study hold criteria, 
irrespective of its relationship with the study medication or the study conduct, the investigator 
must notify the study sponsor as soon as possible (ideally within 2 hours of becoming aware 
of the event) by the following process: 
1. A phone call to the Study Physician to alert them a safety event has been identified. 
2. If the investigator is not able to reach the Study Physician, they should call the 24h rapid 
response helpline number. Upon receipt of a call from an investigator, the 24/7 helpline will 
contact a physician from UCB who will return the call to the investigator. 
3. Additionally, send a completed “Investigator (S)AE Report Form for Development Drug (For 
Rapid Alert Studies)” to the fax/email for Rapid Alert provided at the front of the protocol. 
The form should include assessed seriousness, severity, and causality and should be filed in 
the Study Investigator’s File. 
 
Both the phone call and the completed form from the investigator are crucial in assessing the 
safety of the study medication and in determining whether the event requires immediate 
action to place the study on hold and/or expedite reporting to the regulatory authorities. The 
(S)AE form should be completed in English and provided even if the data are incomplete, or 
if it is obvious that more data will be needed in order to draw any conclusions about the 
diagnosis or causality. Additional information (eg, laboratory reports) received by the 
investigator must be provided within 24 hours. All documents in the local language must be 
accompanied by a translation in English, or the relevant information included in the same 
document must be summarized in English in the (S)AE form. 
During the call between the investigator and the UCB physician the safety issue will be 
discussed to determine if there is sufficient evidence to declare a protocol hold criteria has been 
met. If the investigator and UCB physician agree a stopping a criterion has not been met, dosing 
of the study may continue as per the study protocol and the discussion between the investigator 
and the UCB physician should be documented. UCB will not downgrade the investigator 
decision to halt the study if the investigator considered that a stopping criterion has been 
fulfilled. 
In all other circumstances, the investigator will be instructed to suspend dosing and the UCB 
physician will arrange an urgent, internal UCB Rapid Alert Team meeting. The Rapid Alert 
Team will review the information provided at the call along with the (S)AE form to determine 
whether or not a protocol hold criterion has been met. If it is determined the criterion has not 
been met, UCB will contact the investigator and inform them to recommence dosing. If it is 
determined a hold criterion has been met, UCB will contact all investigators and notify them of 
the formal hold. 
If the investigator believes a protocol stopping criterion has been met, and they are unable to 
contact UCB prior to the next dose being due, they should postpone any further dosing until they 
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have obtained feedback from UCB. In these circumstances dosing may be restarted if UCB and 
the investigator subsequently agree that no stopping criteria have been met. 
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10.9 
Appendix 9: Country specific requirements 
Not applicable 
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10.10 
Appendix 10: Abbreviations and trademarks 
ADA 
anti-drug antibody 
ADE 
adverse device effect 
ADL 
activities of daily living 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC(0-t) 
area under the concentration-time curve from 0 to time t; 
AUC(IgG) 
area under the Total IgG-time curve 
BP 
blood pressure 
CSF 
cerebrospinal fluid 
Cmax 
maximum plasma concentration 
COVID-19 
coronavirus disease-19 
CRO 
contract research organization 
CT 
computed tomography 
ECG 
electrocardiogram 
eCRF 
electronic Case Report form 
FcRn 
neonatal Fc receptor 
GCP 
Good Clinical Practice 
HDL 
high-density lipoprotein 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
ICF 
informed consent form 
IgG 
immunoglobulin G 
IMP 
investigational medicinal product 
ISRQ 
injection site reaction questionnaire 
ITP 
immune thrombocytopenia 
LDL 
low-density lipoprotein 
LLOQ 
lower limit of quantification 
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MG 
myasthenia gravis 
MP 
manual push 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
QTc 
corrected QT 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous(ly) 
SMC 
Safety Monitoring Committee 
SIAQ 
self-injection assessment questionnaire 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
tmin 
time to minimum IgG level 
ULN 
upper limit of normal 
WOCBP 
woman of childbearing potential 
 
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10.11 
Appendix 11: Protocol amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents. 
Amendment 1 (16 Mar 2021) 
Overall Rationale for the Amendment 
The primary reason for this protocol amendment is to incorporate the changes requested by the 
Medicines & Healthcare products Regulatory Agency to the original protocol. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis, Overall 
design 
4.1 Overall design 
The text “with application of the 
Cohort 1 stopping rule (see Section 
6.7)” has been deleted. 
Dosing must be halted if any of the 
stopping criteria are observed in 
any of the study cohorts and not 
only if observed in Cohort 1. 
1.3 Schedule of activities 
Table 1.1: Schedule of activities: 
The row for “Medical history” has 
been deleted. 
The medical history assessment is 
captured in the “Medical/procedure 
history” assessment, and therefore 
this was a duplicated assessment. 
2.3 Benefit/risk assessment The text has been updated to reflect 
that the stopping rules are 
applicable to all cohorts. 
Dosing must be halted if any of the 
stopping criteria are observed in 
any of the study cohorts and not 
only if observed in Cohort 1. 
5.1 Inclusion criteria 
Inclusion criterion #8: This 
criterion has been updated to 
clarify that woman of childbearing 
potential must follow contraceptive 
guidance for at least 90 days after 
the final dose of investigational 
medicinal product (IMP). 
To ensure the duration of 
contraception after the last dose of 
IMP in case of early termination. 
 
5.4 Screen failures 
Updated to clarify that repeat 
laboratory screening tests are not 
restricted to those that were 
out-of-range. In addition, a time 
frame for the repeat assessments  
has been added. 
To clarify that the repeat (visit) 
should be planned within the time 
frame of 28 days between the 
initial screening day and Day 1 
prior to dosing. 
 
6.3.1.2 Breaking the 
treatment blind in an 
emergency situation 
Clarified that the unblinding 
procedure in case of an emergency 
is performed by the investigator. 
The responsibility to break the 
treatment code in emergency 
situations resides solely with the 
investigator. 
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Section # and Name 
Description of Change 
Brief Rationale 
6.7.1 Stopping rules for all 
cohorts 
The title and text have been 
updated to reflect that the stopping 
rules are applicable to all cohorts. 
In addition, it has been clarified 
that further dosing is suspended if 
any of the stopping criteria are met.  
Dosing must be halted if any of the 
stopping criteria are observed in 
any of the study cohorts and not 
only if observed in Cohort 1. 
10.1.5 Committees 
structure 
Updated to include the following 
sentence: “The principal 
investigator will participate in the 
decision of continuing dosing of 
the remaining participants on each 
of these cohorts based on the safety 
data obtained from the sentinel 
participants dosing.” 
The UCB Safety Monitoring 
Committee (SMC) core members 
includes not only UCB members 
but also the principal investigator 
10.8 Appendix 8: Rapid 
alert procedures 
Updated to clarify the sponsor will 
not downgrade the investigator 
decision to halt the study if the 
investigator considered that a 
stopping criterion has been 
fulfilled.  
The investigator is responsible for 
all study-related medical decisions. 
In addition, it has been clarified 
that the stopping rules are 
applicable to all cohorts. 
Dosing must be halted if any of the 
stopping criteria are observed in 
any of the study cohorts and not 
only if observed in Cohort 1. 
 
 
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10.12 
Appendix 12: Suggested management guidelines for infusion 
reactions 
Type of reaction 
Sponsor recommendations for management 
Acute – Mild 
eg, flushing, dizziness, 
headache, sweating, 
palpitations, nausea 
• Stop infusion. 
• Infuse 0.9% sodium chloride 500-1000mL/h IV. 
• Administer antihistamine IV/IM. 
• Administer paracetamol 1g orally. 
• Monitor vital signs every 10 minutes until back to Baseline. In case 
all infusion reaction signs and symptoms have resolved and 
investigator considers infusion restart clinically appropriate, the 
infusion can be restarted; the 
 
 
. 
Acute – Moderate 
eg, flushing, chest tightness, 
dyspnea, hypo/hypertension 
(change >20mmHg in 
systolic blood pressure), 
raised temperature, 
palpitations, urticaria 
• Stop infusion. 
• Infuse 0.9% sodium chloride 500-1000mL/h IV. 
• Administer antihistamine IV/IM. 
• Administer paracetamol 1g orally. 
• Monitor vital signs every 5 minutes until back to Baseline. 
Acute – Severe 
eg, hypo/hypertension 
(change >40mmHg in 
systolic blood pressure), 
raised temperature with 
rigors, chest tightness, 
dyspnea with wheezing, 
stridor 
• Stop infusion. 
• Alert crash team. 
• Maintain airway, ensure oxygen is available. 
• If wheezing, give epinephrine 0.5mg IM (0.5mL 1:1000 
epinephrine). 
• Administer antihistamine IV/IM. 
• Administer corticosteroids IV. 
• Monitor vital signs every 2 minutes until back to Baseline. 
IM=intramuscularly; IV=intravenous; MP=manual push 
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10.13 
Appendix 13: Management of anaphylaxis 
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 1 OF THE FOLLOWING 
− Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia) 
− 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 
study participant (minutes to several hours): 
− Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-
tongue-uvula) 
− Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia) 
− Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) 
− Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
3. 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 that person’s 
Baseline. 
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11 
REFERENCES 
Bienvenu B, Cozon G, Mataix Y, et al. Rapid Push vs Pump-Infused Subcutaneous 
Immunoglobulin Treatment: a Randomized Crossover Study of Quality of Life in Primary 
Immunodeficiency Patients. J Clin Immunol. 2018;38(4):503-12. 
GAMMANORM Package Insert: https://www.medicines.org.uk/emc/files/pil.5658.pdf. 
Gardulf A. Clinical experiences in primary and secondary immunodeficiencies and immune-
mediated conditions using Gammanorm. Immunotherapy; 2016, 8: 633-47. 
HIZENTRA Package Insert: https://www.medicines.org.uk/emc/files/pil.4643.pdf. 
James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of acetaminophen-protein adducts in 
adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 
2009;37(8):1779-84. 
Jolles S. Hyaluronidase facilitated subcutaneous immunoglobulin in primary immunodeficiency. 
Immunotargets Ther. 2013;2:125-33. 
Maeder W, Lieby P, Sebald A, et al. Local tolerance and stability up to 24 months of a new 20% 
proline-stabilized polyclonal immunoglobulin for subcutaneous administration. Biologicals. 
2011;39: 43-9. 
Milota T, Bloomfield M, Karlickova P, et al. Czech Hizentra Noninterventional Study With 
Rapid Push: Efficacy, Safety, Tolerability, and Convenience of Therapy With 20% Subcutaneous 
Immunoglobulin. Clin Ther. 2019;41(11)2231-8. 
Sampson HA, Munoz-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;117:391-7. 
Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 
2007;7(9):715-25. 
Shapiro, R. Subcutaneous immunoglobulin therapy by rapid push is preferred to infusion by 
pump: a retrospective analysis. J Clin Immunol. 2010;30(2):301-7. 
Shapiro R. Why I Use Subcutaneous Immunoglobulin (SCIG). J Clin Immunol. 
2013;33(Suppl 2):S95-8. 
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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:
UP0106-protocol-amend-2
Version:
1. 0
Document Number:
CLIN-000174425
Title:
UP0106 Protocol Amendment 2-Phase 1 placebo-controlled double-blind
Approved Date:
04 Jun 2021
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Medical
Date of Signature: 03-Jun-2021 14:10:54 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 03-Jun-2021 16:00:04 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 04-Jun-2021 07:31:26 GMT+0000
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SAP_001.pdf: 
UCB 
 
1 December 2021 
Statistical Analysis Plan, Final version 2.0,  
Amendment 1 
Rozanolixizumab 
UP0106 
 
 
 
Confidential 
Page 1 of 48 
STATISTICAL ANALYSIS PLAN 
Study: UP0106 
Product: Rozanolixizumab 
A RANDOMIZED, PARTICIPANT-BLIND, INVESTIGATOR-BLIND, PLACEBO-
CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, 
PHARMACOKINETICS, AND PHARMACODYNAMICS OF ROZANOLIXIZUMAB 
ADMINISTERED SUBCUTANEOUSLY VIA MANUAL PUSH VERSUS SYRINGE 
DRIVER TO HEALTHY PARTICIPANTS 
SHORT TITLE: 
A Phase 1 study comparing the safety, tolerability, pharmacokinetics, and pharmacodynamics of 
subcutaneous rozanolixizumab administered via manual push vs syringe driver to healthy 
participants 
Sponsor Name: UCB Pharma SRL 
Legal Registered Address:  
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory Agency Identifier Number(s): 
 
 
 
SAP-Amendment Number 
Date 
Final Version 1.0 
06 May 2021 
Final Version 2.0 
17 August 2021 
Final Version 2.0 / Amendment 1 
1 December 2021 
 
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. 
Registry 
ID 
Eudra CT Number: 
2020-005973-28 
NCT Number 
NCT04828343 
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Statistical Analysis Plan, Final version 2.0,  
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TABLE OF CONTENTS 
VERSION HISTORY ................................................................................................................ 4 
LIST OF ABBREVIATIONS .................................................................................................... 5 
1 
INTRODUCTION ............................................................................................................. 8 
1.1 
Objectives and Estimands/Endpoints ............................................................................. 9 
1.2 
Study design ................................................................................................................. 11 
2 
STATISTICAL HYPOTHESES ...................................................................................... 13 
3 
SAMPLE SIZE DETERMINATION .............................................................................. 13 
4 
POPULATIONS FOR ANALYSIS ................................................................................. 13 
5 
STATISTICAL ANALYSES .......................................................................................... 14 
5.1 
General Considerations ................................................................................................ 14 
5.1.1 
General study level definitions ............................................................................ 16 
5.1.1.1 
Analysis Time Points ................................................................................. 16 
5.1.1.2 
Protocol Deviations ................................................................................... 17 
5.1.1.3 
Treatment assignment and treatment groups ............................................. 17 
5.1.1.4 
Center pooling strategy ............................................................................. 18 
5.1.1.5 
Coding dictionaries .................................................................................... 18 
5.1.1.6 
Multicenter studies .................................................................................... 18 
5.2 
Participant Disposition ................................................................................................. 19 
5.3 
Primary Endpoint(s) Analysis ...................................................................................... 19 
5.3.1 
Definition of endpoint(s) ..................................................................................... 19 
5.3.2 
Main analytical approach ..................................................................................... 19 
5.3.3 
Sensitivity analysis .............................................................................................. 21 
5.3.4 
Supplementary analyses ....................................................................................... 21 
5.4 
Secondary Endpoint(s) Analysis .................................................................................. 21 
5.4.1 
Key/Confirmatory secondary endpoint(s) ........................................................... 21 
5.4.1.1 
Definition of endpoint(s) ........................................................................... 21 
5.4.1.2 
Main analytical approach .......................................................................... 21 
5.4.2 
Supportive secondary endpoint(s) ....................................................................... 23 
5.5 
Exploratory Endpoint(s) Analysis................................................................................ 23 
5.5.1 
Immunogenicity Analyses ................................................................................... 23 
5.5.2 
Exploratory Analyses on the effect of rozanolixizumab on infection specific IgG26 
5.5.3 
Other Exploratory Analyses ................................................................................ 26 
5.6 
Safety Analyses ............................................................................................................ 28 
5.6.1 
Extent of Exposure .............................................................................................. 28 
5.6.2 
Adverse Events .................................................................................................... 28 
5.6.3 
Additional Safety Assessments ............................................................................ 28 
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5.6.3.1 
Clinical laboratory evaluations .................................................................. 28 
5.6.3.2 
Vital Signs ................................................................................................. 29 
5.6.3.3 
Electrocardiograms (ECGs)....................................................................... 30 
5.6.3.4 
Other safety endpoint(s) ............................................................................ 31 
5.7 
Other Analyses ............................................................................................................. 31 
5.8 
Subgroup analyses ....................................................................................................... 32 
5.9 
Interim Analyses .......................................................................................................... 32 
5.10 
Safety Monitoring Committee ..................................................................................... 32 
6 
SUPPORTING DOCUMENTATION ............................................................................. 32 
6.1 
Appendix 1 Non-key analysis specifications ............................................................... 32 
6.1.1 
Baseline characteristics and demographics ......................................................... 32 
6.1.2 
Protocol deviations .............................................................................................. 33 
6.1.3 
Medical history .................................................................................................... 33 
6.1.4 
Prior/concomitant/follow-up medications ........................................................... 33 
6.1.5 
Data derivation rules ............................................................................................ 34 
6.1.5.1 
Laboratory data .......................................................................................... 34 
6.1.5.2 
Pharmacokinetic concentration data .......................................................... 34 
6.1.5.3 
Dates and times ......................................................................................... 34 
6.1.5.4 
Handling of repeated and unscheduled measurements .............................. 37 
6.1.6 
AEs of Special Interest ........................................................................................ 37 
6.1.7 
AEs of Special Monitoring .................................................................................. 38 
6.1.8 
AEs of Focus ........................................................................................................ 38 
6.1.9 
Abnormality Criteria for Laboratory, Vital Sign and Electrocardiogram 
Parameters ............................................................................................................ 39 
6.1.9.1 
Laboratory Assessments Marked Abnormality Criteria ............................ 39 
6.1.9.2 
Vital signs .................................................................................................. 41 
6.1.9.3 
Electrocardiogram (ECG) .......................................................................... 41 
6.1.10 
Compliance .......................................................................................................... 42 
6.2 
Appendix 2: Changes to Protocol-Planned Analyses .................................................. 42 
6.3 
Appendix 3: Adverse Events (AEs) of Focus for the Rozanolixizumab Program ...... 42 
7 
REFERENCES ................................................................................................................ 48 
 
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Statistical Analysis Plan, Final version 2.0,  
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VERSION HISTORY 
SAP Version 
Approval Date 
Change 
Rationale 
1.0 
06 May 2021 
Not Applicable 
Original version 
2.0 
17 August 2021 
Updates following 
protocol amendment 
v2.0 and updates 
following the release 
of the AE of focus 
guideline (v2.0 dated 
24 June 2021). 
Updates to ensure 
consistency in the 
Rozanolixizumab 
program with regards 
to classification of 
concomitant 
medication and 
duration of Adverse 
Events 
Protocol Amendment 
2.0 Amendment 1 
1 December 2021 
Updating the 
reference ranges for 
Serum Calcium and 
the eGFR calculation  
Change in reference 
ranges for the 
clinical program 
 
 
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LIST OF ABBREVIATIONS 
List of Abbreviations 
ADA 
antidrug antibody 
AEOF 
adverse event of focus 
ANOVA 
analysis of variance 
AUC 
area under the concentration-time curve 
AUC(0-t) 
area under the concentration-time curve from 0 to time t 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALQ 
above the limit of quantification 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BLQ 
below the limit of quantification 
BMI 
body mass index 
BP 
blood pressure 
Cmax  
maximum plasma concentration 
COVID-19 
coronavirus disease-19 
CI 
confidence interval 
CRO 
contract research organization 
CSR 
clinical study report 
CV 
coefficient of variation 
DEM 
data evaluation meeting 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
ES 
Enrolled Set 
FDA 
US Food and Drug Administration 
GLSM 
geometric least square mean 
GLSMR 
geometric least square mean ratio 
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List of Abbreviations 
HLT 
high level term 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IgG 
immunoglobulin G 
IMP 
investigational medicinal product 
IPD 
important protocol deviation 
ISRQ 
injection site reaction questionnaire 
LLOQ 
lower limit of quantification 
LSM 
least square mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
MP 
manual push 
MRD 
minimum required dilution 
MSR 
minimum significant ratio 
PCR 
polymerase chain reaction 
PCS 
potentially clinically significant 
PD 
pharmacodynamic 
PD-PPS 
Pharmacodynamic Per Protocol Set 
PDILI 
potential drug-induced liver injury 
PK 
pharmacokinetic 
PK-PPS 
Pharmacokinetic Per Protocol Set 
PT 
preferred term 
QTcF 
QT corrected for heart rate using Fridericia’s formula 
Rmin 
maximum decrease in total plasma IgG 
RS 
Randomized Set 
SAE 
serious adverse events 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous(ly) 
SD 
standard deviation 
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Statistical Analysis Plan, Final version 2.0,  
Amendment 1 
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List of Abbreviations 
SFU 
Safety Follow-up 
SIAQ 
self-injection assessment questionnaire 
SMC 
safety monitoring committee 
SOC 
system organ class 
SS 
Safety Analysis Set 
TEAE 
treatment-emergent adverse event 
TEMA 
treatment-emergent markedly abnormal 
TFLs 
tables, figures, and listings 
tmax  
time to maximum plasma concentration 
tmin 
time to maximum plasma concentration 
ULN 
upper limit of normal 
VAS 
visual analog scale 
WHODD 
World Health Organization Drug Dictionary 
 
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1 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide all information that is necessary 
to perform the required statistical analysis of study UP0106. 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 on, and assumes familiarity, with the following documents: 
• Protocol version- amendment 2, dated 03 June 2021. 
• electronic Case Report Form (eCRF) version 3.0, dated 26 May 2021. 
Unless specified in the sections below, the study will be analyzed as described in the most recent 
version of the protocol. 
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP will be updated accordingly. If, after database lock, additional analyses are 
required to supplement the planned analyses described in this SAP, those unplanned analyses will 
be described in a separate analysis plan. However, if analysis definitions have to be modified or 
updated prior to database lock, a further SAP amendment will be required. 
The content of this SAP is compatible with the International Council for Harmonisation (ICH)/US 
Food and Drug Administration (FDA) E9 Guidance documents. 
UCB is the Sponsor and ICON is the Contract Research Organization (CRO) for this study. 
 
 
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1.1 
Objectives and Estimands/Endpoints 
 
The study objectives and endpoints are presented in Table 1-1. 
Table 1-1: 
Study objectives and endpoints 
Objectives 
Endpoints/Estimands 
Primary 
• To evaluate the safety and 
tolerability of a 
 SC dose of 
rozanolixizumab administered to 
healthy participants by manual push 
(MP) vs syringe driver 
• Incidence of TEAEs 
Secondary 
• To assess the PK and PD of a 
 
SC dose of rozanolixizumab 
administered by MP vs syringe 
driver 
• PK endpoints: 
• Cmax, tmax, AUC(0-t) 
• PD endpoints: 
• Baseline-corrected area under the Total IgG-
time curve 
• Rmin 
• tmin 
Exploratory 
• To compare the PK and PD of a 
 SC dose of rozanolixizumab 
administered by MP vs syringe 
driver 
• PK comparisons: Cmax, AUC(0-t) 
• PD comparison: Baseline-corrected Total IgG 
AUC 
• To evaluate the immunogenicity of 
rozanolixizumab following SC 
administration 
• Anti-rozanolixizumab antibody screening status 
(positive or negative screen), confirmatory 
status (positive or negative immunodepletion), 
and the titer for “positive immunodepletion” 
samples at each scheduled assessment during 
the In-Clinic and SFU Periods 
• To evaluate the effects of 
rozanolixizumab on the 
concentrations of IgG on tetanus, 
influenza A virus-specific IgG 
antibody, and COVID-19 
vaccinated/previously infected 
participants 
• Values and change from Baseline in serum IgG 
concentrations at each scheduled assessment 
during the In-Clinic and SFU Periods 
• Values and change from Baseline in tetanus, 
influenza A virus-specific IgG antibodies, and 
COVID-19 vaccinated/previously infected 
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Table 1-1: 
Study objectives and endpoints 
Objectives 
Endpoints/Estimands 
participants during the In-Clinic and SFU 
Periods 
• To assess total volume, total time, 
and infusion rate for MP and 
syringe driver 
• Volume of IMP administration 
• Time from start to completion and resultant 
infusion rate of IMP administration 
• Time of infusion setup for both modes of 
administration 
• To assess acceptability of SC 
rozanolixizumab administration by 
MP vs syringe driver 
• Post-dose infusion site pain visual analog scale 
with IMP administration 
• To assess the experience with SC 
infusions 
• Pre- and post-dose SIAQ for MP administration 
• Post-dose ISRQ for syringe driver 
administration 
Other Safety 
• To evaluate changes from Baseline 
in vital signs, 12-lead 
electrocardiogram, and laboratory 
measurements following 
 
doses of rozanolixizumab 
administered by SC MP vs syringe 
driver in healthy study participants 
• Vital signs measurements (blood pressure, pulse 
rate, respiratory rate, and body temperature), 
12-lead electrocardiogram, and local tolerability 
assessments at each scheduled assessment 
during the In-Clinic and SFU Periods 
• Changes from Baseline in clinical laboratory 
assessments will consist of hematology 
including coagulation, clinical chemistry, and 
urinalysis at each scheduled assessment during 
the In-Clinic and SFU Periods 
• To further evaluate the safety and 
tolerability of a 
 SC dose of 
rozanolixizumab administered to 
healthy participants by MP vs 
syringe driver 
• Occurrence of serious TEAEs 
• Occurrence of treatment-related TEAEs 
• Occurrence of TEAEs leading to withdrawal 
• Occurrence of AEs of special monitoring 
• Comparison of TEAEs for MP vs syringe driver 
• Serum complement (C3, C4), and cytokines and 
plasma complement (C3a, C5a) 
AE=adverse event; AUC=area under the concentration-time curve; AUC(0-t)=area under the concentration-time 
curve from 0 to time t; Cmax=maximum plasma concentration; COVID-19=coronavirus disease-19; 
IgG=immunoglobulin G; IMP=investigational medicinal product; MP=manual push; ISRQ=injection site reaction 
questionnaire; PD=pharmacodynamic(s); PK=pharmacokinetic(s); Rmin=maximum decrease in total plasma IgG; 
SC=subcutaneous(ly); SFU=Safety Follow-Up; SIAQ=self-injection assessment questionnaire; 
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TEAE=treatment-emergent adverse event; tmax=time to maximum plasma concentration; tmin=time to minimum IgG 
level. 
1.2 
Study design 
This Phase 1 study is a randomized, participant-blind, investigator-blind, placebo-controlled 
safety/tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) evaluation of a 
 
rozanolixizumab subcutaneous (SC) dose administered to healthy participants by either a 
programmed syringe driver or by manual push (MP) via self-administration. As rozanolixizumab 
has not been administered SC to humans by MP, this study represents a preliminary assessment 
of the MP method prior to recommendation of this administration technique in the clinical dosing 
of rozanolixizumab. 
Participants are divided into 2 body weight categories: ≥35 to <50kg and ≥50kg. Within the higher 
body weight category, 16 participants were to be randomly allocated to syringe driver or MP 
cohorts and, subsequently, to rozanolixizumab (6 participants total) or placebo (2 participants 
total) (Figure 1-1). Participants of lighter body weights between ≥35 to <50kg are being 
investigated to a) support the newly recommended rozanolixizumab dosing with a fixed dose of 
 in adults of ≥35kg to 50kg (via syringe driver administration) and (b) to assess the MP 
method for a 
 dose) investigational medicinal product (IMP) volume. 
Within the lower body weight category, the allocation to either syringe driver or MP was to be 
determined by order of recruitment rather than randomization. The first 8 participants were to be 
allocated to the syringe driver cohort and randomly allocated to receive either rozanolixizumab 
 (6 participants total) or placebo (2 participants total). The subsequent 8 participants were 
to be allocated to the MP cohort and randomly allocated to receive either rozanolixizumab 
 
(6 participants total) or placebo (2 participants total). 
The treatment groups were planned as follows: 
• Cohort 1 (participants with a body weight of ≥35kg to <50kg) was planned to have 
6 participants receive rozanolixizumab 
 and 2 participants receive placebo via syringe 
driver at a 
. 
• Cohort 2 (participants with a body weight of ≥35kg to <50kg) was planned to have 
6 participants receive rozanolixizumab 
 and 2 participants receive placebo via MP 
through self-administration at a 
. 
• Cohort 3 (participants with a body weight of ≥50kg) was planned to have 6 participants receive 
rozanolixizumab 
 and 2 participants receive placebo via syringe driver at a 
 
. 
• Cohort 4 (participants with a body weight of ≥50kg) was planned to have 6 participants receive 
rozanolixizumab 
 and 2 participants receive placebo via MP through self-administration 
at a 
. 
Since a 
 rozanolixizumab fixed dose has not been investigated thus far in lower weight (35 
to 50kg) healthy participants, 2 sentinel study participants (1 active + 1 placebo) were to be 
incorporated into Cohort 1 in order to collect safety and tolerability data over a 72-hour period. 
The safety monitoring committee (SMC) is to convene to evaluate all available safety and 
tolerability data following completion of a 72-hour evaluation period and prior to staggered dosing 
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of remaining participants in Cohort 1. As a further precautionary step for Cohort 1, dosing of the 
6 post-sentinel participants was to be staggered such that no more than 2 participants were to be 
dosed in a 72-hour period with a minimum of 48 hours between participants. In addition, the Rapid 
Alert process is in place throughout the study to ensure that exposure to the study medication is 
stopped if a reported event meets the stopping criteria (see protocol Appendix 8 [Section 10.8]). 
Cohorts are not obliged to run in numerical sequence (i.e., cohorts could run in parallel). 
The eligibility of study participants is determined during a Screening Period of up to 4 weeks (Day 
-28 to Day -2). Once eligibility is confirmed, the study participant was to be admitted to the site 
(at Day -1 or the evening of Day -2) and will enter an In-Clinic Period through Day 5. Each study 
participant will receive a 
 SC dose of rozanolixizumab on Day 1 and may be discharged 
beginning at Day 5 at the discretion of the investigator. Each participant will only receive IMP 
administration. 
Beginning at Day 6, study participants will enter the Ambulatory Period and will attend the clinical 
site for study visits through Day 57 to allow sufficient time for systemic immunoglobulin G (IgG) 
levels to return to Baseline and for the assessment of anti-drug antibodies (ADAs). 
The total maximum study duration per study participant is up to 12 weeks. This includes a 4-week 
Screening Period, 5-day In-Clinic Period, and the Ambulatory Period from Day 7 through Day 57. 
Photographs of the infusion site will be taken, without participant personal or facial 
identification, for all participants prior to start and 30 minutes after the end of the IMP 
administration, and additionally upon occurrence of any injection site reaction. 
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Figure 1-1: Study schematic 
 
 
 
2 
STATISTICAL HYPOTHESES 
Not applicable, there is no hypothesis testing in the study. 
 
3 
SAMPLE SIZE DETERMINATION 
No formal statistical sample size calculation has been performed as this study constitutes a 
preliminary assessment of SC rozanolixizumab delivery by MP. The primary objective of the 
study is to evaluate the safety and tolerability of a 
 SC dose of rozanolixizumab administered 
to healthy participants by MP vs syringe driver. A total sample size of approximately 32 
participants randomly assigned to study medication resulting in at least 6 evaluable participants 
per cohort is considered sufficient to meet the primary objective. 
 
4 
POPULATIONS FOR ANALYSIS 
Enrolled Set: The Enrolled Set (ES) will consist of all study participants who have signed the 
Informed Consent Form (ICF). 
Randomized Set: The Randomized Set (RS) consist of all enrolled study participants who were 
randomized. 
Safety 
Follow-up 
Day 57 ± 2 
Ambulatory Days 6 to 57 
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Safety Analysis Set (SS): All randomized study participants who received IMP. Analysis of this 
set will be according to the treatment the study participants actually received and will be used for 
the demographic and safety analyses. 
Pharmacokinetic (PK) Per Protocol Set (PK-PPS): All study participants that received active study 
medication and had at least 1 observable PK measurement and had no important protocol 
deviations affecting the PK parameters. If a study participant in the PK-PPS is missing individual 
time points or are otherwise unobservable, they will be included in the PK-PPS but those time 
points will be omitted from the PK summaries, as appropriate. 
Pharmacodynamic (PD) Per Protocol Set (PD-PPS):  The PD-PPS is a subset of the SS, consisting 
of those study participants who had no important protocol deviations affecting the PD variables, 
as confirmed during a pre-analysis review of the data prior to database lock. 
 
5 
STATISTICAL ANALYSES 
5.1 
General Considerations 
This is a Phase 1 study to evaluate the safety and tolerability of a 
 SC dose of 
rozanolixizumab administered to healthy participants by MP vs syringe driver. 
Statistical evaluation will be performed by UCB or designee with oversight by the Statistical 
Sciences and Innovation Department of UCB. All analyses will be performed using 
SAS® version 9.4 or later (SAS Institute, Cary, NC, USA). 
Missing data will not be imputed. Outlier detection and statistical analysis of outliers will not be 
performed. Unless otherwise stated, Baseline will be the last non-missing data collected prior to 
the IMP administration (refer Section 5.1.1.1.4). 
Continuous variables will be summarized by cohort and in each cohort by treatment groups 
rozanolixizumab 
 or placebo, and day (where applicable); with statistics 
including, the number of study participants, mean, standard deviation (SD), interquartile range, 
median, minimum, maximum, and 95% confidence interval (CI), if applicable. Categorical 
variables will be summarized by cohort, treatment group, and day (where applicable) with 
frequency counts and percentages. Coefficient of variation (CV) and geometric mean will be used 
for PK parameters. 
In addition, the results will be summarized by administration method (manual push or syringe 
driver), and within administration method, by treatment group (rozanolixizumab, regardless of 
dose, or placebo). 
When reporting relative frequencies or other percentage values, the following rules apply: 
• For values where all participants fulfill certain criteria, the percentage value will be 
displayed as 100 
• For values where the absolute frequency is zero, there will be no percentage displayed at 
all 
• All other percentage displays will use 1 decimal place 
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• Percentages displayed based on continuous data (eg, percentage changes from Baseline) 
will be displayed to 1 decimal place eg, 100.0 and 0.0. 
• Unless otherwise stated, the percentages will be based on the number of participants in 
the respective analysis population and treatment group. 
When reporting descriptive statistics, the following rules will apply in general:  
• “n” will be an integer. 
• Mean (arithmetic and geometric), 95% CI, SD, and median will use 1 additional decimal 
place compared to the original data. 
• Coefficient of variance (CV [%]) will be presented with 1 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, then only n=0 will be presented. If n<3, 
only the n, minimum, and maximum will be presented. If n=3, only the n, median, 
minimum, and maximum will be presented. The other descriptive statistics will be left 
blank. 
When reporting descriptive statistics for PK data, the following rules will apply with regard 
to rounding and precision: 
• Individual values for PK concentration data will be reported to the same level of precision 
as received from the bioanalytical laboratory. 
• Descriptive statistics for PK concentration data will be reported to the same level of 
precision as the individual data for the minimum and maximum, and to 1 additional 
significant figure for the mean (arithmetic and geometric), median, SD, and 95% CI for 
the geometric mean.  
• Individual values for PK parameters will be reported to 3 significant figures. 
• Descriptive statistics for PK parameters will be reported to 3 significant figures for 
minimum and maximum and to 4 significant figures for the mean (arithmetic and 
geometric), median, SD, and 95% CI for the geometric mean. 
• Geometric CV will be reported as a percentage to 1 decimal place. 
• When the mean value includes one or more replaced BLQ values then a footnote should 
be included to say “contains one or more BLQ value replaced by half the LLOQ value” 
• A minimum of 3 values are required to calculate summary statistics. If only 2 values are 
available then these should be presented as the minimum and maximum with other 
descriptive statistics reported as missing (“-“). 
Additional rules regarding handling of values that are BLQ are presented in Section 6.1.5.2.  
 
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5.1.1 
General study level definitions 
5.1.1.1 
Analysis Time Points 
5.1.1.1.1 
Relative day 
The relative day of an event will be derived with the date of dosing as reference. Relative days for 
an event or measurement occurring before the date of dosing are calculated as follows: 
  
Relative Day = [(Event Date – Date of Dosing)] 
The relative day for an event or measurement occurring on the date of dosing is 1 and is calculated 
as follows: 
  
Relative Day = [(Event Date – Date of Dosing) + 1] 
For events or measurements occurring after the date of dosing, relative day will be prefixed with 
‘+’ in the data listings and will be calculated as follows: 
  
Relative Day = + [(Event Date – Date of Dosing)] 
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 relevant listing. 
 
5.1.1.1.2 
Study periods 
The following study periods are defined: 
Pre-treatment Period: This period is defined as the period prior to the date of first dose of IMP. 
The period ends at the day prior to the date of IMP administration. 
In-Clinic Period: This periods starts at the date of first dose of IMP (Day 1) and ends on the date 
of discharged from the clinical study center (Day 5). 
Ambulatory Safety Follow-Up Period: This period starts at the day after the date of discharge 
(Day 5) and ends at study completion(i.e. Day 6 through Day 57). 
 
5.1.1.1.3 
Mapping of assessments performed at Early Discontinuation Visit 
Participants who withdraw from the study will be encouraged to return to the clinic to complete 
the Withdrawal Visit.  
The following rules will apply regarding the inclusion of data obtained at the early discontinuation 
visit in the summaries and in the data listings: 
• If the early discontinuation occurs at the time of the next scheduled visit, the results will 
be included with all other participants’ results from that visit. 
• If the early discontinuation visit does not correspond to the day of a scheduled visit, the 
results will be mapped to the nearest scheduled visit following the last scheduled visit 
where assessments were performed. 
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• If the date of the early discontinuation visit is equidistant between 2 scheduled visits at 
which no scheduled assessments were performed, the results from the withdrawal visit 
will be mapped to the earliest of these visits. 
The results from the early discontinuation visit will be displayed as the mapped visit and will be 
flagged in the data listings. 
 
5.1.1.1.4 
Definition of Baseline values 
In general, Baseline will be the last non-missing value prior to dosing. Scheduled or unscheduled 
measurements can be used as the Baseline value.  
 
5.1.1.2 
Protocol Deviations 
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the PK, PD and key safety for an individual study 
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 data cleaning process and all important deviations will be identified and documented before 
unblinding to confirm exclusion from analysis sets. 
After all data have been verified/coded/entered into the database, a blinded data review will be 
performed prior to database lock, at a Data Evaluation Meeting (DEM). The purpose of this review 
meeting will be to examine all protocol deviations, define the PK-PPS and PD-PPS, and to verify 
the quality of the data. The data evaluation will also help in guiding decisions on how to manage 
data issues on a case by case basis (e.g., missing values, dropouts, and protocol deviations). 
Protocol deviations (e.g., missing assessments or visits) related to coronavirus disease-19 
(COVID-19) will be listed separately and will be reviewed for the definition of the PK-PPS and 
PD-PPS analysis sets. 
All Important Protocol Deviations (IPDs) will be discussed and documented at the DEM together 
with any decisions regarding exclusion from analysis sets. If necessary, appropriate actions will 
be implemented in the SAP amendment before locking the database. After the DEM, resolution 
of all issues, and documentation of all decisions, the database will be locked. 
 
5.1.1.3 
Treatment assignment and treatment groups 
Treatment assignment for the SS, PK-PPS and PD-PPS will be according to the actual treatment 
received. Listings and summaries will be presented by cohort and treatment group.  
The following label conventions and order will be used in the TFLs (except for PK analysis)  
• Cohort 1 - ≥35kg to <50kg, Syringe driver 
o Placebo via Syringe Driver 
o Rozanolixizumab 
Syringe Driver  
• Cohort 2 - ≥35kg to <50kg, MP 
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o Placebo via MP 
o Rozanolixizumab 
 MP 
• Cohort 3 -≥50kg, Syringe driver 
o Placebo via Syringe Driver 
o Rozanolixizumab 
 Syringe Driver  
• Cohort 4 -≥50kg, MP 
o Placebo via MP 
o Rozanolixizumab 
 MP 
• 
Syringe Driver, All Participants  
o Placebo 
o Rozanolixizumab 
• MP, All Participants  
o Placebo 
o Rozanolixizumab 
 
The following label conventions and order will be used in the PK TFLs: 
• Rozanolixizumab via Syringe Driver, All  
• Rozanolixizumab via MP, All 
The explanatory description of each cohort may be dropped from the labels if space is limited. 
For listings, the cohort description and the treatment name will be written out in full. 
 
5.1.1.4 
Center pooling strategy 
Not applicable, this is a single center study. 
 
5.1.1.5 
Coding dictionaries 
Adverse events and medical history will be coded using Version 23.1 of the Medical Dictionary 
for Regulatory Activities (MedDRA®). Medications will be coded according to the World Health 
Organization Drug Dictionary (WHODD). Medical procedures will not be coded. 
 
5.1.1.6 
Multicenter studies 
This is a single center trial, therefore this section is not applicable. 
 
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5.2 
Participant Disposition 
The number of participants who were enrolled, randomized into the study, included in each 
analysis set, and completed or prematurely discontinued from the study, as well as the reason for 
discontinuation, will be summarized by cohort and treatment group. 
Screen failure reasons will be summarized based on the ES.  
In addition, the following listings will be presented by cohort and treatment group: 
• Participant disposition (ES) 
• Participant analysis sets (ES) 
• Participant discontinuing from the study  (RS) 
• Study visit dates (RS) 
The listing of participants disposition will include the date of informed consent, date of 
randomization, date and time of dosing, date of premature study termination, primary reason for 
premature discontinuation (if applicable), date of final contact, and date of premature unblinding 
and reason for code break (if applicable). 
The listing of study discontinuation will include the reason for discontinuation and the number 
of days since dosing. 
The number and percentage of study participants who discontinued due to adverse events (AEs) 
will be summarized separately by cohort and treatment group, based on the randomized 
participants. This will be used for European Union Drug Regulating Authorities Clinical Trials 
(EudraCT) reporting. 
 
5.3 
Primary Endpoint(s) Analysis 
The primary endpoint is: 
• Incidence of Treatment-emergent adverse event (TEAE). 
 
5.3.1 
Definition of endpoint(s) 
A TEAE is defined as any AE with a start date/time on or after first dose of study medication until 
8 weeks after dosing of study medication (termination or withdrawal visit) .  
 
5.3.2 
Main analytical approach 
All AEs and serious adverse events (SAEs) will be collected from the signing of the ICF until the 
Safety Follow-up/Withdrawal Visit. All AEs will be coded (Section 5.1.1.5) and categorized by 
intensity (mild/moderate/severe) and relationship to study drug (related/not related). Only TEAEs 
will be included in the summary tables and listings. 
 
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The number and percentage of participants who experience TEAEs will be summarized by cohort, 
treatment group, system organ class (SOC) and preferred term (PT) based on the safety analysis 
set. Summaries of TEAEs will include the following: 
• Overview of TEAEs (overview including number and percentage of participants with any 
TEAEs, serious TEAEs, discontinuations due to TEAEs, drug-related TEAEs, severe 
TEAEs, TEAEs of special interest and TEAEs leading to death; event counts will also be 
included)  
• Incidence of TEAEs 
• Incidence of TEAEs leading to study medication interruption 
• Incidence of serious TEAEs 
• Incidence of non-serious TEAEs 
• Incidence of TEAEs by relationship to study medication 
• Incidence of TEAEs by maximum relationship to study medication 
• Incidence of TEAEs by intensity 
• Incidence of TEAEs by maximum intensity 
• Incidence of non-serious TEAEs by relationship 
• Incidence of serious TEAEs by relationship 
• Incidence TEAEs of special interest 
• Incidence of TEAEs of Focus (see Appendix 6.1.8 ) 
• Incidence of TEAEs of special monitoring 
• Incidence of TEAEs by TE ADA status 
 
In case of missing or incomplete dates, AEs will be assumed to be treatment-emergent and will 
be handled as described in Section 6.1.5.3.  
Summary tables will contain counts of participants, percentages of participants (in parentheses), 
and the number of events where applicable. A participant who has multiple events in the same 
SOC and PT will be counted only once in the participant counts but all events will be included.   
In summaries including relationship, the following relationships will be summarized: ‘not related’, 
‘related’. Participants who experience the same event multiple times will be included in the most 
related category for tabulations by maximum relationship. Events with missing relationship will 
be considered as ‘related’ but recorded as missing in the listings.   
Adverse event summaries will be ordered alphabetically by SOC and decreasing frequency of PT 
within SOC in the ”Rozanolixizumab” cohort 1 column for tables including event counts. For 
tables including only number and percentage of participants, summaries will be ordered 
alphabetically by SOC and decreasing incidence of PT within SOC in the “Rozanolixizumab” 
column.  
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A listing will be presented by treatment group for all AEs and will include the onset date/time and 
outcome date/time of the event (including relative days), the AE duration (derived), pattern of 
event, intensity, relationship, action taken and outcome. In addition, the listing will flag AEs that 
led to discontinuation, TEAEs, and SAEs. 
 
5.3.3 
Sensitivity analysis 
No sensitivity analysis is planned for this study. 
 
5.3.4 
Supplementary analyses 
No supplementary analysis is planned for this study. 
 
5.4 
Secondary Endpoint(s) Analysis 
5.4.1 
Key/Confirmatory secondary endpoint(s) 
PK endpoints 
- 
Maximum plasma concentration  (Cmax) 
- 
Time to maximum plasma concentration (tmax) 
- 
Area under the concentration-time curve from 0 to time t (AUC(0-t)) 
PD endpoints: 
- 
Baseline-corrected area under the Total IgG-time curve 
- 
Maximum decrease in total plasma IgG (Rmin) 
- 
Time to minimum IgG level (tmin) 
- 
Total IgG 
 
5.4.1.1 
Definition of endpoint(s) 
Pharmacokinetics will be determined by non-compartmental analysis in Phoenix WinNonlin  
(Certara, USA) using the PK Per Protocol Set.  
For calculation of the plasma PK parameters of rozanolixizumab, the actual sampling time points 
along with the actual dose administered and duration of administration will be used in order to 
evaluate the PK parameters. 
Venous blood samples will be collected at protocol specified time points for the measurement of 
Total IgG. 
 
5.4.1.2 
Main analytical approach 
PK analyses 
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All PK summaries will be done using PK-PPS and displayed by method of administration (see 
section 5.1.1.3). The plasma concentration-time profiles and PK parameters of rozanolixizumab 
(C_max, AUC, and T_max) will be summarized by method, dose and body weight for 
rozanolixizumab treated patients using descriptive statistics (number of available observations, 
arithmetic mean, standard deviation, the geometric mean, the coefficient of variation of the 
geometric mean, median, minimum, and maximum). For tmax , only median, minimum and 
maximum will be reported. Values below LLOQ will be reported with a clear sign indicating that 
they were below the LLOQ. Descriptive statistics of concentrations will be calculated if at least 
two-thirds of the individual data points are quantifiable (≥LLOQ). 
Individual and spaghetti concentration time profiles will be displayed graphically on a linear-linear 
scale and semi-logarithmic scale. Geometric mean plasma concentrations-time curves including 
95% CI will be displayed.  
The comparability of dose-adjusted PK parameters (Cmax/D and AUC(0-t)/D) between the methods 
(MP and the syringe driver) will be assessed within an analysis of variance (ANOVA) model with 
method (MP vs syringe driver) as a main effect, with no additional covariates. The log-transformed 
PK parameters will be used in the ANOVA model. The model structure to be used is therefore 
log⁡(𝑃𝑎𝑟𝑎𝑚𝑒𝑡𝑒𝑟)⁡~⁡𝑀𝑒𝑡ℎ𝑜𝑑⁡𝑜𝑓⁡𝐴𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑟𝑎𝑡𝑖𝑜𝑛 
This model structure has been chosen to reflect the intended dosing scheme of fixed dosing (e.g., 
of 
) applied to adults >35kg irrespective of weight. This will thus allow us to draw 
conclusions about the presence or absence of effects of the method of dose administration on 
parameter values when given using the intended scheme. Any potential effect of weight on 
parameter values will be accounted for by the study design itself by the balanced proportion of 
lower weight/higher weight participants receiving their dose using each of MP and Syringe driver.  
 
The geometric least square mean (GLSM), GLSM differences and the corresponding 90% CI for 
the differences (MP [Test] - syringe driver [Reference]) will be calculated for PK parameters (log-
transformed Cmax, AUC0-t). Back-transformed (anti-log) estimates of (GLSM,  geometric least 
square mean ratio (GLSMR) and its 90% CI for the comparisons will be presented. In order to 
verify the normality assumption of the ANOVA, normal quantile-quantile plots will be used to 
visually inspect the distribution of residuals, and the potential impact of any deviations will be 
discussed.  
PD analyses 
All PD summaries will be done using PD-PPS by treatment group described under section 5.1.1.3. 
Total IgG (observed values, change from Baseline, and percentage change from Baseline) will be 
listed and summarized for the PD Per Protocol Set. The geometric mean Total IgG concentration 
with 95% CI will be displayed graphically. 
Derived parameters for the Total IgG response curve (AUC, maximum decrease in total plasma 
IgG, and time to minimum plasma concentration) will be listed and summarized for the PD Per 
Protocol Set. 
The comparability of the total dose adjusted IgG Baseline-corrected AUC (IgG)/D between MP 
and the syringe driver will be assessed within an ANCOVA model with Baseline IgG value fitted 
as a covariate. The least square mean (LSM), LSM differences and the corresponding 95% CI for 
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the differences will be presented for total IgG. The analysis may be conducted on the log scale if 
the data exhibits substantial non-normality. In this case, the reason for the log-transformation will 
be described.  
The following contrasts will be presented: 
• Rozanolixizumab via Syringe Driver vs Rozanoliximab via MP 
• Placebo via Syringe Driver vs Placebo via MP  
• Rozanolixizumab via Syringe Driver vs Placebo via Syringe Driver 
• Rozanoliximab via MP vs Placebo via MP 
 
Additionally, observed values and change from Baseline in serum IgG concentrations at each 
scheduled assessment during the In-Clinic and SFU Periods will be summarized descriptively.  
 
5.4.2 
Supportive secondary endpoint(s) 
Not applicable no supportive secondary analysis is planned for this study. 
 
5.5 
Exploratory Endpoint(s) Analysis 
Exploratory endpoints related to the comparison of PK and PD parameters are covered under 
section 5.4. 
5.5.1 
Immunogenicity Analyses 
The development of antidrug antibodies during the study will be evaluated to assess the 
immunogenicity potential of the study drug. 
The anti-drug (rozanolixizumab) antibody (ADA) screening status (positive or negative screen), 
confirmatory status (positive or negative immunodepletion), and the titer for “positive 
immunodepletion” samples at each scheduled assessment during the In-Clinic and SFU Periods 
will be presented. 
The results of the ADA analyses will be listed and summarized by cohort treatment group (refer 
section 5.1.1.3) and time point for the SS.  
Anti-drug antibodies will be measured using a three-tiered assay approach: screening assay, 
confirmatory assay and titration assay. All immunological analyses will be exploratory. 
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 minimum required dilution (MRD)).  
The ADA status should be determined for each visit where samples were taken for ADA analysis. 
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• Sample values that are either ‘negative screen’ or ‘positive screen’ and ‘negative immune 
depletion’ will be defined as ADA negative. 
• Sample values that are ‘positive screen’ and ‘positive immune depletion’ will be defined 
as ADA positive. 
In addition, the anti-drug antibody status will be further classified based on participant levels as 
outlined below. This classification should be done for entire study duration (i.e. the treatment 
period including SFU sampling time point). 
1. Pre ADA negative – treatment induced ADA negative: Includes participants who 
are negative at Baseline and antibody negative at all sampling points post treatment. 
This group also includes participants who have a missing pretreatment sample (either 
missing or insufficient volume) at Baseline with all ADA post-treatment samples 
negative. 
2. Pre ADA negative – treatment induced ADA positive: Includes participants who are 
negative at Baseline and antibody positive at any sampling point post treatment. This 
group also includes participants who have a missing pretreatment sample (either 
missing or insufficient volume) at Baseline with one or more ADA positive post-
treatment samples. 
3. Pre ADA positive – treatment reduced ADA: Includes participants who are positive 
at Baseline, and antibody negative at all sampling points post treatment.  
4. Pre ADA positive – treatment unaffected ADA: Includes participants who are 
positive at Baseline and are positive at any sampling point post treatment with titer 
values of the same magnitude as Baseline (ie, less than a predefined fold difference 
increase from the Baseline value, i.e. the minimum significant ratio (MSR) determined 
during assay validation). 
5. Pre ADA positive – treatment boosted ADA positive: Includes participants who are 
positive at Baseline and are positive at any sampling point post treatment with 
increased titer values compared to Baseline (greater than a predefined fold difference 
increase from Baseline value, i.e. the MSR determined during assay validation). 
6. Inconclusive: Includes participants who have a positive or negative pretreatment 
sample and at least one post-treatment samples are missing, while other post-treatment 
samples are ADA negative. 
Based on the overall ADA participant classification above, the following will be determined and 
presented in tables: 
• Total prevalence of pre-Antibody: n/N % number of participants that are pre ADA positive, 
i.e. from categories 3, 4, 5. 
• Total incidence of treatment-emergent ADA positive: n/N % number of participants in 
category 2 and category 5. 
The following summaries, figures and listings will be produced and will be presented:  
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− Summary table displaying the number and percentage of participants with a positive ADA 
status and negative ADA at the time of each visit by cohort and treatment group.  
− Summary tables displaying the number and percentage of participant in each of the ADA 
participant categories (1 – 6), total prevalence of pre-Antibody and total incidence of 
treatment-emergent ADA positivity as defined above by cohort  treatment group. 
Spaghetti plots of ADA titer (y-axis) by visit (x-axis). This plot will include the following ADA 
participant categories: 
a) Category 2: Pre ADA negative – treatment-induced ADA positive 
b) Category 4: Pre ADA positive – treatment unaffected ADA positive  
c) Category 5: Pre ADA positive – treatment-boosted ADA positive 
All categories will be presented on the same plot (visualized using different colors). Plots will be 
presented using a semi-logarithmic scale for the ADA titers (ADA negative samples will therefore 
be excluded from the plot). 
A listing of anti-rozanolixizumab antibodies will include all derived results. 
 
 
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Serum complement (C3, C4) and cytokines and plasma complement (C3a, C5a) 
Listing will be provided for serum complement (C3, C4) and cytokines and plasma complement 
sampling details (C3a, C5a). 
 
5.5.2 
Exploratory Analyses on the effect of rozanolixizumab on infection specific 
IgG 
Observed values at baseline and at SFU and change from Baseline to SFU in IgG concentrations 
will be summarized descriptively for each treatment group for the following virus specific IgG 
concentrations 
Tetanus specific IgG 
Influenza A virus-specific IgG antibodies, 
SARS Cov-2 antibodies for COVID-19 vaccinated and/or previously infected participants  
 
For SARS-COV-2 antibodies, the summary table will present one row for vaccinated participants, 
a second row for previously infected participants, and a final row for those with both (if any). 
In addition to the summary table, the data for the above specific antibodies will be listed for all 
the collected timepoints. 
 
5.5.3 
Other Exploratory Analyses 
• 
Post-dose infusion site pain visual analog scale (VAS) with IMP administration 
The visual analog scale of injection site pain indicates the level of pain at the site of 
injection. It reaches from 0-100 mm with higher values for more severe pain and 0 for no 
pain. 
Participants VAS (mm) will be summarized using descriptive statistics based on the SS by 
cohort and treatment group, and by method of infusion (Manual push/Safety syringe) and 
treatment group (rozanolixizumab, regardless of dose, or placebo). 
• 
Pre-dose self-injection assessment questionnaire (SIAQ) for MP administration 
There are 2 modules for the SIAQ: SIAQ PRE-Self-Injection and SIAQ POST-Self-Injection.  
The SIAQ PRE-Self-Injection will be completed pre-dose by participants in the MP cohorts 
only. 
It consists of 7 items each with a scale of 1 to 5. There are three individual domains (feelings 
about injections [FL, 3 items], self-confidence [CO, 3 items] and satisfaction with current 
mode of administration [SA, 1 item]). Each domain score will be calculated as the average of 
the individual transformed item scores. The item scores will be transformed using the 
following rule: 
Transformed Item Score= ((raw item score)-1)×2.5 
In the case of missing values, a domain score will be calculated only if 50% or more of the 
items within the domain are completed. 
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The domain scores range from 0 to 10, higher scores indicate more confidence, higher 
satisfaction and less concerns with self-injections. 
Participants pre-dose SIAQ domain scores will be summarized using descriptive statistics 
based on the SS by cohort and treatment group, and by treatment group only (rozanolixizumab, 
regardless of dose, or placebo). 
• 
Post-dose self-injection assessment questionnaire (SIAQ) for MP administration 
The SIAQ POST-Self-Injection will be completed 30 minutes to 1 hour post-dose by 
participants in the MP cohorts only.   
It consists of 21 items on 6 individual domains (FL [3 items], self-image [IM, 1 item], CO [3 
items], injection-site reactions [RE, 2 items], ease of use [EU, 5 items] and satisfaction with 
self-injection [SA, 7 items]). The items of the individual domain EU have a score range of 1 
to 6, the items of the other individual domains have a score range of 1 to 5. Each domain 
score will be calculated as the average of the individual transformed item scores.  
The item scores for the EU domain will be transformed using the following rule: 
Transformed Item Score= ((raw item score)-1)×2 
The item scores for the other domains will be transformed using the following rule: 
Transformed Item Score= ((raw item score)-1)×2.5 
In the case of missing values, a domain score will be calculated only if 50% or more of the 
items within the domain are completed. 
The domain scores range from 0 to 10, higher scores indicate more confidence, higher 
satisfaction and less concerns with self-injections. 
Participants post-dose SIAQ domain scores will be summarized using descriptive statistics 
based on the SS by cohort and treatment group, and by treatment group only (rozanolixizumab, 
regardless of dose, or placebo).  
• 
Post-dose injection site reaction questionnaire (ISRQ) for syringe driver administration 
The ISRQ will be completed 30 minutes to 1 hour post-dose by participants (syringe driver 
cohorts only).  
The ISRQ consists of the items from the individual domain RE of the SIAQ POST-Self-
Injection. The ISRQ score will be calculated as the average of the individual transformed item 
scores. The item scores will be transformed using the following rule: 
Transformed Item Score= ((raw item score)-1)×2.5 
In the case of missing values, the ISQR score will be calculated only if 50% or more of the 
items are completed. 
The ISQR score ranges from 0 to 10, higher score indicates less concerns with the injections. 
Participants post-dose ISRQ score will be summarized using descriptive statistics based on 
the SS by cohort and treatment group, and by treatment group only (rozanolixizumab or 
placebo). 
 
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5.6 
Safety Analyses 
All safety analyses will be performed using the SS. 
 
5.6.1 
Extent of Exposure 
All IMP administration details (including date/time of administration and volume administered) 
will be listed by treatment group and participant. The listing will include the start and stop time of 
the drug administration, the duration (derived) and details regarding any interruptions/ 
discontinuations including the reasons, if applicable. 
 
Since the IMP administration consists of a 
 dose, duration of exposure will not be calculated. 
 
5.6.2 
Adverse Events 
See  Section 5.3 for a description of the analysis and reporting of adverse events. 
 
5.6.3 
Additional Safety Assessments 
5.6.3.1 
Clinical laboratory evaluations 
Laboratory data (hematology, clinical chemistry, and urinalysis) and changes from Baseline (if 
applicable) for numeric variables will be listed by cohort, treatment group and time point. Only 
abnormal laboratory values will be listed. In case of any abnormal value, all values for the 
respective subject on this laboratory parameter will be listed. 
Any laboratory measurements that are BLQ or above the limit of quantification (ALQ) will be 
handled as described in Section 6.1.5.1. Values outside the reference range for numeric variables 
will be flagged in the listings and in addition, will be listed separately for each lab category 
(hematology, chemistry and urinalysis). The reference ranges will also be reported in the listings.  
Laboratory measurements satisfying the marked abnormality criteria (see Section 6.1.9.1 ) will be 
flagged.  
Screening tests (as specified in Appendix 2 of the protocol ) will be listed in a separate listing.  
 
5.6.3.1.1 
Laboratory values over time 
Laboratory variables are grouped according to the laboratory function panel (see Appendix 2 of 
the protocol). Observed laboratory variables and changes from Baseline will be summarized by 
descriptive statistics at each time point by cohort, treatment group and method of administration 
based on SS. In addition, TEMAs for hematology and for clinical chemistry abnormalities will be 
summarized by treatment group and visit. 
 
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5.6.3.1.2 
Individual Participant Changes of Laboratory Values 
Laboratory variables will be categorized as normal, high or low, if applicable, based on the 
reference range supplied by the analytical laboratory. The change in category from Baseline will 
be presented in shift tables at all post-Baseline time points per cohort, treatment group and method 
of administration (refer section 5.1.1.3). 
 
5.6.3.1.3 
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 summarized by treatment group and visit.  
 
PDILI Criteria: 
  
- Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥5x Upper limit of 
normal (ULN)  
- ALT or AST increase ≥3x ULN and Total bilirubin ≥2x ULN  
- (ALT or AST increase ≥3x ULN) and Total bilirubin ≥2x ULN and ALP <2 x ULN  
- (ALT or AST ≥3x ULN) and (eCRF question for “Is the subject exhibiting we symptoms of 
hypersensitivity” = Yes or eCRF question for “Is the subject exhibiting symptoms of. Hepatitis” 
= Yes at the same date +/-2 days).  
- (ALT or AST) ≥3xULN (and ≥2x Baseline) and <5xULN and Total bilirubin <2xULN and 
(eCRF question for “Is the subject exhibiting symptoms of hypersensitivity” = No and eCRF 
question for “Is the subject exhibiting symptoms of Hepatitis” = No at the same date +/-2 days)  
- (ALT or AST) ≥5xULN (and ≥2x Baseline) and Total bilirubin <2xULN (eCRF question for 
“Is the subject exhibiting symptoms of hypersensitivity” = No and eCRF question for “Is the 
subject exhibiting symptoms of Hepatitis” = No at the same date +/-2 days)  
 
A listing will also be created 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. 
 
5.6.3.2 
Vital Signs 
The following vital signs measurements will be obtained with the participant resting in a supine 
position after 5 minutes rest:  
• Pulse rate 
• Systolic and diastolic blood pressure (BP) 
• Temperature (tympanic) 
• Respiratory rate 
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A by-participant listing of all vital sign measurements and change from Baseline will be presented 
by cohort and timepoint. The listing will include a flag for measurements identified as treatment-
emergent markedly abnormal (TEMA) as calculated by the criteria outlined in Section 6.1.9.2. 
 
 
5.6.3.2.1 
Vital Sign Values Over Time 
Descriptive statistics will be reported for all vital sign measurements. Measured values and 
changes from Baseline will be summarized by vital signs variables and timepoint for each cohort, 
treatment group and method of administration (refer section 5.1.1.3).  
 
5.6.3.2.2 
Individual Participant Changes of Vital Sign Values 
The number and percentage of participants with TEMA vital sign values will be summarized by 
cohort, treatment group and method of administration(refer section 5.1.1.3) at each timepoint.  
 
5.6.3.3 
Electrocardiograms (ECGs) 
All ECG recordings should be taken before any blood sampling (except at the end of infusion) 
and with the study participant resting in the supine position for at least 5 minutes before the 
recording. 
The following ECG parameters will be reported: 
• Heart rate 
• PR interval  
• QRS interval 
• QT interval 
• QT corrected for heart rate using Fridericia’s formula (QTcF) 
The individual measurements will be reported in the by-participant listings. The listing will also 
include the observed results, change from Baseline at each timepoint, and will be presented by 
cohort, treatment group, method of administration (refer section 5.1.1.3) and timepoint. 
A listing of ECG findings, for participants with abnormal (whether or not clinically significant) 
results will be presented by cohort, treatment group, method of administration and time point. 
ECG abnormality criteria can be found in Section 6.1.9.3. 
 
5.6.3.3.1 
Electrocardiogram Values Over Time 
Measured values and changes from Baseline values will be summarized by cohort, treatment group 
(refer section 5.1.1.3) at each timepoint and by ECG variable.  ECG TEMAs will be summarized 
by treatment group and visit.  
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5.6.3.3.2 
Individual Participant Changes of Electrocardiograms Values 
The following cut-points in QTcF (raw data and change from Baseline) data will be summarized 
categorically (number and percentage of participants) by cohort, treatment group (refer section 
5.1.1.3) at each timepoint. 
For raw data: 
• <450msec  
• ≥450 to <480msec  
• ≥480 to <500msec 
• ≥500msec 
Absolute change from Baseline in QTcF: 
• <30msec 
• ≥30 to <60msec 
• ≥60msec 
 
5.6.3.4 
Other safety endpoint(s) 
Physical examination and body weight 
Participants with abnormalities in the physical examination will be listed including details of the 
abnormality. 
 
Photographs of Injection Site:  
Details of whether photographs were taken, prior to start and 30 minutes after the end of the IMP 
administration, and the date if so, will be listed for each subject and study visit. Any additional 
photograph taken upon occurrence of any injection site reaction will also be listed. 
 
Local tolerability of SC infusion 
Assessment of local tolerability of SC infusion (by the investigator or designee) will be completed 
post-dose, at the end of infusion, and  4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after the start of 
infusion. Summary and listings will be provided for the tolerability reaction details. 
 
5.7 
Other Analyses 
No other analyses (including genomics) have been planned for this study. 
 
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5.8 
Subgroup analyses 
Not applicable, no subgroup analyses are planned for this study 
5.9 
Interim Analyses 
No formal interim analyses are planned for this study. 
 
5.10 
Safety Monitoring Committee  
As per the protocol defined cohort description, two sentinel study participants (1 active + 1 
placebo) will be incorporated into Cohort 1 and a SMC will convene to evaluate all available 
safety and tolerability data following completion of the 72-hour evaluation period and prior to 
dosing of the remaining participants in Cohort 1. 
An Operational Plan will be agreed between ICON and UCB to detail the timelines, data flow and 
review processes leading up to, and on the critical path for each SMC. The analysis of these safety 
data are outside the scope of this analysis plan. 
 
6 
SUPPORTING DOCUMENTATION 
6.1 
Appendix 1 Non-key analysis specifications 
6.1.1 
Baseline characteristics and demographics 
A by-participant listing of demographics will be presented by cohort and treatment group (refer 
section 5.1.1.3) based on the ES. This will include the year of birth, age (in years), sex, race, 
ethnicity, height (in cm), weight (in kg) and body mass index (BMI). The height will be obtained 
only at screening. Body mass index in kg/m2 is calculated based on the height (in m) and the 
weight (in kg) using the following formula: 
BMI (kg/m2) = weight (kg)/[height (m)]2 
The BMI will be reported to 1 decimal place. 
All demographic characteristics (with the exception of year of birth) will be summarized by cohort 
and treatment group based on the SS. The summary of age will include descriptive statistics and 
categorical summaries, the latter based on requirements for EudraCT and clinicaltrials.gov 
reporting. For the EudraCT reporting, the categories will include: 
• 18 to <65 years 
• 65 to <85 years 
• ≥85 years 
For clinicaltrials.gov reporting, the categories will include: 
• ≤18 years 
• 19 to <65 years 
• ≥65 years 
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Other Baseline characteristics  
Lifestyle information (alcohol and illicit drugs) will be listed by cohort and treatment group (refer 
section 5.1.1.3) for the SS.  
Childbearing Potential and Birth Control will be listed for the SS. 
 
6.1.2 
Protocol deviations 
Important protocol deviations will be identified and classified by the deviation types in the IPD 
document.  
A listing of all IPDs identified at the DEM and deviations related to COVID-19 will be presented 
based on the RS, and will include the deviation type and description. The number and percentage 
of participants in the RS with IPDs will be summarized by cohort and treatment group (refer 
section 5.1.1.3). The denominator for the percentages will be the number of participants in the RS. 
In addition, deviations related to COVID-19 will also be summarized. 
The following information from the severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2) testing polymerase chain reaction (PCR) CRF form will be displayed in a separate listing: 
status of PCR test performed, date of sample, test result, impacted visit and date of visit, the impact 
category, relationship with COVID-19 and the narrative of event. The number and percentage of 
the impact categories will be summarized by cohort, treatment group and visit for the RS. 
 
6.1.3 
Medical history 
Medical history will be listed and summarized (in an incidence table) for the SS by cohort, 
treatment group (refer section 5.1.1.3) and MedDRA SOC and PT.  
Procedure history will be listed separately by cohort treatment group and the procedure reported 
term for the SS. 
6.1.4 
Prior/concomitant/follow-up medications 
Prior and concomitant medications will be listed and summarized (in an incidence table) for the 
SS by cohort and treatment group (refer section 5.1.1.3), by WHODD Anatomical Main Group 
(Level 1 term text), Pharmacological Subgroup (Level 3 term text) and PT. The reported term will 
be included in the listing. Separate tabulations will be presented for prior medications and 
concomitant medications. Prior medications which are started prior to medication and continued 
after the treatment will also be classified as concomitant and will be included in both summaries. 
Any prohibited concomitant medications (as defined in protocol section 6.5.2) will be identified 
via a medical review and flagged in this listing.    
Past medications are defined as any medications that started prior to the first administration of 
study drug and stopped prior to dosing. 
Concomitant medications includes any medication that has been taken at least once on or after 
the date of first administration of study drug (also referred to as new onset of concomitant 
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medications). Permitted concomitant medications are limited to those listed in section 6.5.1 of the 
protocol.  
Prior and Concomitant medications (also referred to as Baseline medications) will include 
any medications that started prior to dosing and continued after (classified as prior and 
concomitant medications).  
 
Two summary tables will be produced; a table summarizing all  medications that started prior to 
the first administration of study drug which will include all “past medications” and all  “prior & 
concomitant medications”, and a table summarizing all concomitant medications which will 
include all “concomitant medications” and all “prior & concomitant medications”. In addition a 
listing will be produced. Any medications with missing dates and/or times will be handled as 
described in Section 6.1.5.3 in order to classify them as prior or concomitant. 
 
6.1.5 
Data derivation rules 
6.1.5.1 
Laboratory data  
Safety laboratory measurements that are BLQ will be imputed with half of the LLOQ for the 
purpose of calculating change from Baseline and for the summaries and figures. Measurements 
ALQ, if applicable, will be imputed to the upper quantification limit. 
 
6.1.5.2 
Pharmacokinetic concentration data  
Concentrations that are BLQ will be imputed with half of the LLOQ for the purpose of calculating 
the geometric mean and its 95% CI, the geometric CV, the arithmetic mean and SD for summaries 
and figures. For this purpose missing values should be excluded. Descriptive statistics of 
concentrations will be calculated if at least two-third of the individual data points are quantifiable 
(≥LLOQ). 
For all individual PK concentration plots any values that are BLQ will be imputed with half of the 
LLOQ, with the exception of pre-dose BLQ values (linear scale only) which will be imputed as 
zero. 
6.1.5.3 
Dates and times  
Partially or completely missing dates may be imputed for the following reasons: 
• 
Classification of AEs as treatment-emergent 
• 
Classification of medications as past, prior or concomitant 
• 
Duration of AEs 
Imputed dates will not be shown in the listings; all dates will be displayed as reported in the 
database. 
The following rules will be applied for partially or completely missing start dates: 
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• If year, month and day are all missing then assign the date of IMP administration. If an 
imputed start date is after the specified end date, then assign January 01 of the year of the 
end date, or the date of screening if this is later (if the latter imputation results in an end 
date that is earlier than the start date, then use January 01). 
• If month and day are missing, and year is: 
− the same as the year of IMP administration then assign the month-day of IMP 
administration. If the imputed start date is after the specified end date, then assign 
January 01, or the month-day of screening date if this is later (if the latter imputation 
results in an end date that is earlier than the start date, then assign January 01); 
− not the same as the year of the IMP administration then assign January 01. 
• If only day is missing, and month-year is: 
− the same as the month-year of the IMP administration then assign the day of IMP 
administration. If the imputed start date is after the specified end date, then assign first 
day of the month, or the day of screening date if this is later (if the latter imputation 
results in an end date that is earlier than the start date, then assign first day of the 
month); 
− not the same as the month-year of the first dose of IMP then assign the first day of the 
month. 
If AE occurred on the same day as treatment start date, but with missing time, time will be imputed 
as the same time as treatment start time; If AE occurred prior or after treatment start date but with 
missing time, time will be imputed as 00:00h. If the start time of medication is missing, this will 
be imputed as 00:00h.  
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, then use discharge date or data cut-off date. 
Note: Discharge date refers to the date of the end of study visit for completed study participants 
or the date of discontinuation for study 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 date. For study 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.  
Any medication with a start date on the first dosing date and time unknown, will be assumed to be 
concomitant. 
Missing or partially missing dates and/or times will be imputed as described in Table 6-1 for the 
calculation of duration of each AE. Adverse event duration is computed in and reported in day and 
time format: xx d hh:mm. 
 
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Table 6-1: Calculation rules for duration of AEs 
Data Availability 
Onset Date/ 
Time 
Outcome 
Date/ Time 
Calculation Rules 
Complete data 
D1/T1 
D2/T2 
Duration = [(D2 – D1)*24 + (T2 – 
T1)]/24 days 
End time missing 
D1/T1 
D2/-- 
End time is substituted by time 23:59h 
(=23.98 in decimal format). 
Duration = <[(D2 – D1)*24 + (23.98 – 
T1)]/24 days 
Start time missing 
D1/-- 
D2/T2 
Onset time is substituted by 00:00h. 
Duration = <[(D2 – D1)*24 + T2]/24 
days. In case of an AE starting  on the 
study drug intake day but with missing 
time, the time  imputed is the dosing 
time and this time should be used for the 
duration calculation. For AE starting on 
a different days then study drug intake, 
then take 00:00. 
Start and end time 
missing  
D1/-- 
D2/-- 
Duration = < (D2 – D1) + 1 days 
Start day and time 
missing 
--/-- 
D2/T2 
Duration = < [(D2 – D0)*24 + (T2 – 
T0)] / 24 days 
For a participant in the SS, D0 and T0 
are the date and time of administration 
of IMP and for screen failures, D0 = the 
screening visit date and T0 = 0. If the 
imputed start date is after the specified 
end date, then assign January 01 of the 
year of the end date, or the date of 
screening if this is later (if the latter 
imputation results in an start date that is 
after  the end date, then use January 
01)”. 
 
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Data Availability 
Onset Date/ 
Time 
Outcome 
Date/ Time 
Calculation Rules 
End day and time 
missing  
D1/T1 
--/-- 
For ongoing AE duration = > Discharge 
day – D1 (days) For resolved AE 
duration = < Discharge day – D1 (days) 
where discharge refers to the date of the 
Safety Follow-up visit or date of 
discontinuation. For any AEs with 
known start date/time after the date of 
discontinuation, the date of last contact 
will be used as the discharge day. 
Start and end date 
missing 
--/-- 
--/-- 
For ongoing AE duration = > Discharge 
day – D0 (days) For resolved AE 
duration = < Discharge day – D0 (days) 
where discharge refers to the date of the 
Safety Follow-up visit or date of 
discontinuation. For a participant in the 
SS, D0 is the date of administration of 
IMP and for screen failures, D0 =the 
screening visit date. 
6.1.5.4 
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 measurements obtained prior to dosing the latest value (which may be 
scheduled or unscheduled) will be used in the calculation of the descriptive statistics. 
• 
For repeated measurements obtained at the designated Baseline visit, the latest values 
(which may be scheduled or unscheduled) will be defined as the Baseline provided that 
the measurement occurred prior to dosing. 
 
6.1.6 
AEs of Special Interest 
An AE of special interest (AESI) 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. For rozanolixizumab, the following events require 
immediate reporting (within 24 hours regardless of seriousness) to UCB: 
• Potential Hy’s Law, defined as ≥3× upper limit of normal (ULN) alanine aminotransferase 
(ALT) or aspartate  aminotransferase  (AST) with coexisting ≥2×ULN total bilirubin in 
the absence of ≥2×ULN alkaline phosphatase (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. 
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6.1.7 
AEs of Special Monitoring 
In addition, AEs of special monitoring have been identified. 
These include: 
• Severe headache 
Participants suffering from severe headache are requested to complete the headache 
questionnaire daily until the headache has been resolved. The results of this questionnaire 
will be listed.   
For participants with severe headache a neurological assessment may be performed at the 
investigators discretion. In addition a lumbar puncture for CSF collection and a CT scan 
may be performed. The results of these additional assessments will be listed as well. 
• Severe gastrointestinal disturbances (i.e. abdominal pain, diarrhea or vomiting) 
Study participants who experience moderate or severe diarrhea will have a stool sample 
collected and analysed. The results of the stool sampling will be listed. 
• Opportunistic infection 
The number and percentage of participants who experience AEs of special monitoring and who 
experience AEs of special interest will be summarized by cohort, treatment group, and method of 
administration, SOC and PT based on the SS. The  A listing will be presented by cohort and 
treatment group for all AEs of special interest/monitoring. Additionally symptoms and  frequency 
of severe headaches will be listed. 
 
6.1.8 
AEs of Focus 
 
The following AEs are defined in the Rozanolixizumab  program as AEs of focus (please see 
Appendix 3 for more details)  
− Headaches 
− Gastrointestinal Disturbances 
− Hypersensitivity Reactions 
− Anaphylactic Reactions 
− Injection Site Reactions 
− Infusion Reactions 
− Infections 
− Opportunistic Infections 
− Reductions in Albumin and Plasma Proteins 
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− Effects on the Kidney 
− Drug Related Hepatic Disorders 
− Effect on lipids 
 
AEOFs will be summarized by treatment group to tabulate the following: 
• Incidence of each AEOFs by SOC, High Level Group Term (HLGT), HLT and PT 
• Incidence of each Serious AEOFs by SOC, High Level Group Term (HLGT), HLT 
and PT 
• Incidence of each AEOFs by relationship, SOC, HLGT, HLT and PT 
• Incidence of each AEOFs by maximum intensity, SOC, HLGT, HLT and PT 
 
6.1.9 
Abnormality Criteria for Laboratory, Vital Sign and Electrocardiogram 
Parameters 
6.1.9.1 
 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 Common Terminology Criteria 
for Adverse Events (CTCAE) grade 3 or higher criteria unless otherwise noted. If both high and 
low criteria are shown for a parameter, the criteria should be summarized separately in tabular or 
graphical data summaries. 
 
6.1.9.1.1 
Hematology 
 
PARAMETER 
UNIT 
(conven
tional) 
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  
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). 
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2For blinded ITP protocols, Platelets will not be assessed for TEMA because this parameter will be blinded and is 
expected to be abnormally low due to the participant population and entry criteria.  
 
6.1.9.1.2 
Chemistry 
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  
GGT (Gamma 
Glutamyl 
Transferase) 
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 m 
mL/min/1.73 m 
eGFR <29 mL/min/1.73 m 
C reactive protein 
(CRP)2 
mg/L 
mg/L 
>10mg/L 
Calcium 
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 
Immunoglobulin G3  
(g/L) 
(g/L) 
≤1 g/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 
Glucose4 
mg/dL 
mmol/L 
Low: <40 mg/dL; <2.2 mmol/L  
High: > 250 mg/dL; >13.9 mmol/L 
Total Cholesterol 
mg/dL 
mmol/L 
>400 mg/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 CTCAE, Version 5.0  
unless otherwise noted.  
1eGFR is calculated using the Chronic Kidney Disease Epidemiology Collaboration or CKD-EPI formula 
(https://qxmd.com/calculate/calculator_251/egfr-using-ckd-epi) 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 
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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. For derivation from values in standard units (umol/L) 
the κ values are 61.88 for females and 79.56 for males.s 
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/. A 
moderate elevation of CRP level per referred reference is used for the marked abnormality criteria for RLZ to 
ensure a change suggestive of inflammatory process is captured. 
3Immunoglobulin G criterion based on immunodeficiency literature and noted in RLZ study protocols. 
4Glucose high criterion defined by Grade 3 and higher events according to CTCAE, Version 4.03, June 14, 2010. 
 
6.1.9.2 
Vital signs 
Abnormality criteria to be applied in the assessment of vital signs parameter values are given 
below. 
 
 
6.1.9.3 
Electrocardiogram (ECG) 
Abnormality criteria to be applied in the assessment of ECG parameter values are given below: 
Parameter 
Abnormality Criteria 
QT interval (ms) 
 
>500ms 
≥60ms increase from Baseline 
QTc(F) (ms) 
>500ms 
≥60ms increase from Baseline 
PR interval (ms) 
Treatment-emergent value >200ms 
QRS interval (ms) 
Treatment-emergent value >100ms 
Heart rate (bpm) 
<50bpm 
>120bpm 
Abbreviations: 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 after the first infusion of 
study medication and within 56-days of the last infusion and not meeting the same criteria during Baseline 
 
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 
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6.1.10 
Compliance 
Designated site personnel will ensure treatment compliance by overseeing SC infusion of the IMP 
by the participant. Drug accountability must be recorded on the Drug Accountability form. Any 
incomplete administration of IMP will require documentation of how much was infused (including 
start and stop times). 
As a measure of compliance the percentage of the planned dose administered will be calculated 
based on the planned and delivered infusion volume:  
Percentage of planned dose administered (%) = [100*(actual volume/planned volume)]  
 
The actual dose administered will be calculated as: 
Actual dose (mg) = (planned dose* (percentage of planned dose administered/100)). 
The actual volume delivered, percentage of planned dose administered, actual dose (mg), 
duration of infusion (minutes) will be summarized descriptively. In addition the number of 
participants with infusion temporarily stopped and the number of participants with infusion 
permanently discontinued will be summarized. 
A listing on compliance data will be prepared. 
 
6.2 
Appendix 2: Changes to Protocol-Planned Analyses 
 
As per protocol “All safety variables will be analyzed by descriptive methods and presented by 
treatment (rozanolixizumab or placebo), method (MP or syringe driver), body weight, and dose 
level.” However, the analysis were planned by cohort and treatment group as per the SAP 
section 5.1.1.3. All other analysis were planned as per the protocol. 
 
6.3 
Appendix 3: Adverse Events (AEs) of Focus for the Rozanolixizumab 
Program 
 
 
The purpose of this document is to detail the approach to identifying TEAEs meeting criteria for 
AEs of focus (AEOF) for the Rozanolixizumab (also called Rozimab) program.  
 
The document is organized by MedDRA version. At the time of writing this document, 
MedDRA version 22.0 was planned to be used for all indications under investigation (MG, ITP, 
CIDP, HV). As there is no change between 22.0 and 22.1 and 23.0 and 23.1 and 24.0 regarding 
terms used in below selection criteria, all below specified algorithms apply to these MedDRA 
versions.  If future studies are planned which use a different (more recent) version of MedDRA, 
this document will be updated. 
 
MedDRA SMQ file 24.0: 
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SMQ_spreadsheet_
24_0_English.xlsx  
Following Events are Adverse Event of focus For Rozimab for all indications: 
 
No Event (also included in 
Title of TFL output) 
Selection criteria 
Purpose 
CSR/ 
SSD/ IB 
1 
Headache 
(Note: also included in 
AESM if severe) 
TEAE with HLGT=’Headaches’ 
CSR/ 
SSD/ IB 
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)’ 
CSR/ 
SSD/ IB 
3 
Hypersensitivity reactions  
 
SMQ=’Hypersensitivity’ 
CSR/ 
SSD/ IB 
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 
CSR/ 
SSD/ IB 
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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. 
 
5 
Injection site reactions 
TEAE with 
HLT=’Injection site reactions’ or 
HLT=’Infusion site reactions’ or 
HLT=’Administration site reactions NEC’ 
CSR/ 
SSD/ IB 
6 
Infusion Reactions  
Infusion reaction marked on AE CRF page 
(based on the assessment by the 
Investigator) 
CSR/ 
SSD/ IB 
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 
CSR/ 
SSD/ IB 
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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]  
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. 
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 [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. 
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’ 
CSR/ 
SSD/ IB 
10 
Effects on the kidney 
TEAEs in  
SMQ= ‘Acute renal failure’ 
CSR/ 
SSD/ IB 
11 
Drug related hepatic 
disorders  
TEAEs in  
CSR/ 
SSD/ IB 
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UCB 
 
1 December 2021 
Statistical Analysis Plan, Final version 2.0,  
Amendment 1 
Rozanolixizumab 
UP0106 
 
 
 
Confidential 
Page 47 of 48 
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’ 
CSR/ 
SSD/IB  
 
For each of above-mentioned AEs of focus following analysis will be done: 
Analysis 
Table shell 
Incidence of AEOF xxx 
AE_T_02  
Incidence of AEOF xxx by Relationship  AE_T_04b  
Incidence of serious AEOF xxx 
AE_T_02  
Incidence of AEOF xxx by Maximum 
Intensity 
AE_T_03A  
 
 
 
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UCB 
 
1 December 2021 
Statistical Analysis Plan, Final version 2.0,  
Amendment 1 
Rozanolixizumab 
UP0106 
 
 
 
Confidential 
Page 48 of 48 
The following output will only be requested as needed and will not be produced routinely: 
Incidence of TEAEs by Outcome, Time to onset of AEOF, Duration of AEOF, Kaplan-Meier 
plots of time to the first AEOF, AEs occurring 24hrs prior to TEAE of headache and 24hrs after 
 
The standard medical history table should be updated to include HLGT or otherwise a separate 
medical history table need to be created to show all medical histories with HLGT=Headaches 
 
For all indications for SSD/IB and CSR delivery: 
A general Lab and AE excel file will be created (basically ADAE and ADLB as excel but 
limited by variables that will be shown in the standard listing) and named as AEOF ADxx 
YYYYMMDD 
For ITP indication for final CSR TFLs delivery: 
1. A separate Laboratory excel file for platelets need to be created for subjects with a 
platelet decrease of 10x109/L or more after last Study Medication compared to baseline 
value. Suggested name for excel “AEOF Subjects who have a Change in Platelets from 
Baseline <= -10x109/L after last Study Medication YYYYMMDD 
Following variables should be included in Lab Listing: 
• Patient ID,  
• Actual Treatment group 
• Baseline Study medication dose,  
• Duration of the treatment 
• Last Study medication dose 
• Last PLT at the last study visit 
• Period 
• Visit 
• Date and Time of Measurement 
• Baseline PLT 
• PLT at Visit 
• Change from Baseline 
• Time to platelet drop after last IMP datetime. 
• Flag for Change <= - 10x109/L 
2. A separate AE excel file for Haemorrhages (SMQ) starting after last IMP date 
(=occurring in observation period)  
3. A separate AE excel file for Haematopoietic thrombocytopenia (SMQ) starting after last 
IMP date (=occurring in observation period)  
 
7 
REFERENCES 
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002. 
 
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Approval Signatures
Name:
up0106-sap-amend-1
Version:
1. 0
Document Number:
CLIN-000181418
Title:
UP0106 SAP Amendment 1
Approved Date:
01 Dec 2021
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 01-Dec-2021 09:23:40 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 01-Dec-2021 10:16:17 GMT+0000
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