Conditions: Fibromyalgia
Keywords: Phase 2 Fibromyalgia rozanolixizumab
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 63
Healthy volunteers: no

Brief summary:
The purpose of the study is to evaluate efficacy and safety of rozanolixizumab to treat adult study participants with severe fibromyalgia syndrome (FMS).

Detailed description:

Arms:
arm 1: Study participants on Treatment sequence 1 will receive rozanolixizumab and Placebo during the dosing period at pre-specified timepoints. arm 2: Study participants on Treatment sequence 2 will receive rozanolixizumab and Placebo during the dosing period at pre-specified timepoints. arm 3: Study participants on Treatment sequence 3 will receive Placebo during the dosing period at pre-specified timepoints.

Interventions: intervention 1: rozanolixizumab intervention 2: Placebo
Intervention descriptions: intervention 1: Study participants will receive rozanolixizumab during the dosing periods as pre-defined. intervention 2: Study participants will receive Placebo during the dosing periods as pre-defined.

Protocol document:
Prot_000.pdf: 
UCB 
 
14 Apr 2023 
Clinical Study Protocol Amendment 3 
Rozanolixizumab 
FM0001 
 
 
 
Confidential 
Page 1 of 116 
 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PHASE 2A, PROOF-OF-CONCEPT STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF 
ROZANOLIXIZUMAB TO TREAT ADULT STUDY 
PARTICIPANTS WITH SEVERE FIBROMYALGIA SYNDROME 
 
PROTOCOL AMENDMENT 3 FM0001 
PHASE 2A 
 
SHORT TITLE: 
A Phase 2A proof-of-concept study to evaluate the efficacy and safety of rozanolixizumab to 
treat adult study participants with severe fibromyalgia syndrome 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying number(s): 
EudraCT Number: 
2022-001523-32 
IND Number: 
Not applicable 
NCT Number: 
Not applicable 
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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Clinical Study Protocol Amendment 3 
Rozanolixizumab 
FM0001 
Confidential 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document History 
Document 
Date 
Type of amendment 
Protocol Amendment 3 
14 Apr 2023 
Substantial 
Protocol Amendment 2 
29 Nov 2022 
Substantial 
Protocol Amendment 1 
24 Oct 2022 
Substantial 
Original Protocol 
23 Jun 2022 
Not applicable 
Amendment 3 (14 Apr 2023) 
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 main reason for this amendment is to adjust the inclusion/exclusion criteria in order to better 
reflect the characteristics of the population with fibromyalgia syndrome (FMS). Additional 
changes have been made to update and simplify the protocol based on safety knowledge gained 
from the rozanolixizumab program and to adjust the wording of the statistical section with the 
current version of the Statistical Analysis Plan (SAP). 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
1.3 Schedule of activities 
3. Objectives and
endpoints
9.4.1 Safety analyses 
Change from Baseline in 
electrocardiogram (ECG) results 
was removed from the exploratory 
endpoints, as ECG will be 
performed only before dosing 
(screening and Visit 3).  
Electrocardiograms at Visit 15, 27, 
and End of Treatment (EOT)/Early 
Withdrawal (EW) were removed. A 
footnote was added to specify that a 
12-lead ECG can be performed any 
time during the study at the 
investigator’s discretion. 
Change from Baseline in ECG was 
removed from the analyses. 
Exclusion criterion #33, related to 
QT interval, was removed. 
Monoclonal antibodies do not 
directly gain access to the cell 
cytosol and are too large to bind to 
the potassium channel encoded by 
the human ether-a-go-go related 
gene (hERG) known to play a key 
role in repolarization of the 
ventricular cardiac action potential. 
Rozanolixizumab is, therefore, not 
expected to induce a prolongation 
of the action potential duration 
leading to prolongation of the QT 
interval and cardiac arrhythmia, and 
no cardiac events are expected 
adverse drug reactions from review 
of data across the program. Twelve-
lead ECG will still be performed at 
screening and may be performed at 
any time if deemed necessary by 
the investigator. 
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Clinical Study Protocol Amendment 3 
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FM0001 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
1.3 Schedule of activities 
3. Objectives and 
endpoints 
8.9.2 Immunology 
9.4.2.4 Immunological 
analyses 
10.2 Appendix 2: Clinical 
laboratory tests 
The objective ‘to assess the effects 
of rozanolixizumab on 
immunoglobulin (Ig)A, IgE, and 
IgM levels’, the associated 
endpoint, and scheduled activities 
as well as related text were 
removed throughout the document. 
As no impact on serum levels of 
IgA, IgE, and IgM are expected 
based on the pharmacology of 
rozanolixizumab and no clinically 
meaningful changes in IgA, IgE 
and IgM levels following the 
administration of rozanolixizumab 
or any other neonatal Fc receptor 
(FcRn) inhibitor have been 
observed in any clinical study of 
rozanolixizumab to date, 
assessments of these 
immunoglobulin classes are no 
longer deemed necessary for the 
safety monitoring of the study 
participants. 
1.1 Synopsis 
4.1 Overall design 
In the overall design description, 
the number of study centers was 
increased from 6 to 8. 
To allow the inclusion of additional 
study centers.  
1.1 Synopsis 
7.2.1 Study withdrawal 
criteria 
8.3.5 Pregnancy 
Description of the safety follow-up 
period was slightly reworded. 
The procedures to be completed if a 
study participant withdraws was 
adapted as follows: 
“SFU or EOS Visit should be 
scheduled 6 weeks after the study 
participant has discontinued his/her 
IMP in the Run-out Period.” 
Clarification. 
2.1 Study rationale 
4.1 Overall design 
5.1 Inclusion criteria 
In the study rationale, text was 
added to provide newly published 
evidence demonstrating that 
fibromyalgia patients with elevated 
levels of anti-satellite glia cell 
(SGC) IgG antibodies present with 
higher levels of self-reported pain. 
In the overall study design 
description, study population was 
updated (pain intensity change from 
≥5 to ≥6, removal of Revised 
Fibromyalgia Impact Questionnaire 
(FIQR) score ≥64 and Fatigue 
numeric rating scale (NRS) score 
≥5).  
Inclusion criterion #3a (now 3b) 
was updated to remove completion 
of pain management program of at 
To better reflect the recently 
published findings on fibromyalgia 
and the current clinical practices in 
term of pain management in the 
population of patients with severe 
fibromyalgia, as well as reduce 
protocol complexities.  
 
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Clinical Study Protocol Amendment 3 
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FM0001 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
least 36 hours duration performed 
>6 months before study entry date, 
FIQR score≥64 and fatigue NRS 
score≥5. Range for mean daily 
average 24h pain intensity was 
updated (from ≥5 and <10 to ≥6 
and <10). 
1.3 Schedule of activities 
6.5.1 Permitted 
concomitant treatments 
In the Schedule of activities, 
completion of pain management 
program was added as part of the 
information to be collected as 
general medical/procedure history. 
Pain management programs were 
added to the treatments permitted 
during the study, providing they are 
considered acceptable in the 
judgment of the investigator and in 
discussion with the medical 
monitor. 
As a pain management program is 
no longer part of the eligibility 
criteria, information related to pain 
management program are collected 
along with medical history for 
exploratory purposes. 
1.3 Schedule of activities 
5.1 Inclusion criteria 
5.4 Screen failures 
7.1.4 Temporary 
discontinuation 
Coronavirus disease 2019 
(COVID-19) vaccination status and 
testing was removed from the 
Schedule of Activities table. 
Inclusion criterion #8, related to 
COVID-19 vaccination, was 
removed. 
Text related to COVID-19 was 
removed in the Screen failures 
section. 
Text related to temporary 
discontinuation in the event of 
COVID-19 was removed. 
To update and simplify the protocol 
based on safety knowledge gained 
from the rozanolixizumab program 
during and after the COVID-19 
pandemic. 
1.3 Schedule of activities 
5.2 Exclusion criteria 
7.1.2 Other permanent 
discontinuation criteria 
7.2.1 Study withdrawal 
criteria 
8.2.6 Assessment and 
management of 
tuberculosis and 
tuberculosis risk factors 
8.2.7 Suicidal risk 
monitoring 
In Schedule of Activities, 
Section 8.2.6, and Section 10.12, 
tuberculosis (TB) signs and 
symptoms questionnaire was 
removed and replaced by focused 
medical history. 
In Schedule of Activities and 
Section 10.12, interferon gamma 
release assay (IGRA) test was 
modified from mandatory to 
optional. Related footnotes in the 
schedule of activities were updated 
accordingly. The footnote for 
physical examination was updated 
To clarify and simplify text related 
to diagnosis, assessment and 
management of TB. The prior focus 
on TB within the protocol was 
standard text for UCB protocols for 
immunomodulator drugs but gave 
undue prominence to the topic 
considering the mechanism of 
action of rozanolixizumab. 
Rozanolixizumab is not expected to 
inhibit the generation of an immune 
response or have effects on the B-
cell repertoire (eg, on plasma cells 
or memory B cells), or to interfere 
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Clinical Study Protocol Amendment 3 
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FM0001 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
10.12 Appendix 12: 
Assessment and 
management of 
tuberculosis and 
tuberculosis risk factors 
 
to include an assessment of 
potential signs and symptoms of TB 
and risk factors for exposure to TB. 
Exclusion criterion #13 (Study 
participant has positive TB test at 
the Screening Visit) was removed. 
Exclusion criterion #14 (now 14a), 
requirements for latent tuberculosis 
infection (LTBI) and 
nontuberculous mycobacterial 
(NTM) infection, were updated. 
Treatment for LTBI was reduced 
from 4 weeks to 1 week and 
“current NTM infection or history 
of NTM infection unless proven to 
be fully recovered” was removed. 
Text related to NTM infection was 
removed as covered by exclusion 
criterion #9a. 
Text on the assessment and 
management of TB was moved 
from Section 8.2.6 to Section 10.12 
Appendix 12. In addition, new text 
on safety reporting requirements 
related to TB was added. 
Consequently, Section 8.2.7 
Suicidal risk monitoring was 
renumbered to Section 8.2.6. 
with other cells of the innate and 
adaptive immune systems or 
complement. Because of its discrete 
mechanism of action, FcRn 
inhibition is less likely to be 
associated with increased risk of 
infection compared with other 
immunomodulators and unlikely to 
lead to opportunistic infections with 
intracellular pathogens, particularly 
those requiring granulomatous 
inflammation for control (eg, 
mycobacteria, fungi) (Peter et al, 
2020). 
1.3 Schedule of activities 
8.1.3 Pressure pain 
threshold 
In the Schedule of activities, 
footnote was added on pressure 
pain threshold assessment to clarify 
assessment should be done predose. 
This was also specified in the 
description of study procedures. 
Clarification. 
1.3 Schedule of activities 
8.2.3 Vital signs 
Reduction in the number of vital 
sign assessment (blood pressure, 
pulse rate and temperature) during 
the treatment period. 
The considered study population 
has a chronic pain condition 
characterized by widespread pain 
and increased pain sensitivity to 
mechanical pressure; thus, blood 
pressure monitoring can be very 
painful. The study protocol was 
consequently adapted based on the 
recent safety knowledge gained 
from the rozanolixizumab program 
and feedback from a FMS clinical 
expert. 
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Rozanolixizumab 
FM0001 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
4.1 Overall study design 
5.1 Inclusion criteria 
8.1.2 Pain NRS 
 
Clarification that, during the 
Screening Period, 1) the assessment 
of the pain intensity at Screening 
should be performed over a 10-day 
period within the Screening Period. 
2) Study participants require a 
minimum of 7 out of 10 daily Pain 
NRS assessments to be eligible for 
randomization.  
Clarification. 
5.1 Inclusion criteria 
Inclusion Criterion #5a (now 5b) 
Males was added to clarify that 
both males and females can be 
enrolled in the study. 
Clarification. 
5.2 Exclusion criteria 
Exclusion criterion #7 (related to 
clinically significant finding in 12-
lead ECG) was removed as it was 
covered under exclusion criterion 
#3. 
Exclusion criterion #25 (now 25a), 
time since last vaccination with a 
live vaccine, was reduced from 8 
weeks to 4 weeks (changes were 
also made in Table 6-2: Prohibited 
concomitant medications). 
To update the exclusion criteria 
based on gained safety knowledge 
on rozanolixizumab, to align with 
current therapeutic practices, and to 
remove redundancies, as some 
provisions are adequately captured 
by other eligibility criteria. 
 
5.2 Exclusion criteria 
Exclusion criterion #9 (now 9a) has 
been modified to limit the exclusion 
of a participant due to a current 
active infection, an unresolved, or 
an inadequately treated infection. 
Exclusion criterion #20, related to 
IgA deficiency was removed. 
 
Infection exclusion criterion 
language simplified but intent to 
exclude clinically relevant infection 
retained. 
No impact on serum levels of IgA, 
IgE, and IgM are expected based on 
the pharmacology of 
rozanolixizumab and no clinically 
meaningful changes in IgA, IgE 
and IgM levels following the 
administration of rozanolixizumab 
or any other FcRn inhibitor have 
been observed in any clinical study 
of rozanolixizumab to date. 
5.2 Exclusion criteria 
Exclusion criterion #15 (study 
participant has any of the following 
active gastrointestinal (GI) 
disorders: inflammatory bowel 
disease, GI ulceration, or 
diverticulitis) was removed. 
 
The accumulated safety data on 
rozanolixizumab led to an update of 
the adverse events of special 
monitoring (AESM) (ie, previous 
removal of the former AESM of 
severe GI disorders) and 
reconsideration of study exclusion 
criteria with corresponding removal 
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FM0001 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
of the exclusion criterion relating to 
active GI disorders. 
5.2 Exclusion criteria 
8.2.6 Suicidal risk 
monitoring 
Exclusion criterion #21 (now 21a) 
was updated to shorten from 5 to 2 
years the period of time before 
screening visit which the study 
participants had a suicide attempt. 
 
With a chronic pain disorder, 
fibromyalgia patients suffer from 
high rates of comorbid anxiety and 
depression, which are risk factors 
for suicidal behaviors. Study 
participants at serious or active 
suicide risk will be excluded from 
the study with recommended 
referral for appropriate intervention 
as assessed by the investigator's 
clinical judgment, the participant's 
history of suicide attempt(s), and/or 
responses to the Columbia-Suicide 
Severity Rating Scale (C-SSRS) 
questionnaire administered at 
Screening. 
6.5.1 Permitted 
concomitant treatments 
(medications and 
therapies) 
Dose and class of concomitant 
medications permitted during the 
study duration have been clarified. 
To better reflect the current 
practices in term of pain 
management in the population of 
patients with severe fibromyalgia. 
8 Study assessments and 
procedures 
The paragraph related to procedures 
conducted as part of participant’s 
routine clinical management that 
may be utilized for 
Screening/Baseline purposes have 
has been removed. 
Correction as all data obtained 
before signing of the ICF will be 
considered as historical data and 
will not be utilized for Screening or 
Baseline purpose. 
8.3 Adverse events and 
serious adverse events 
The following sentence was added: 
"For results disclosure on public 
registries (eg, ClinicalTrials.gov), 
TEAEs and treatment-emergent 
SAEs will be published”. 
Clarification. 
9.1 Definition of analysis 
sets  
Clarification that the Safety Set-as 
randomized (SS-r) will be utilized 
for the analyses of demographics 
and immunogenicity. 
Clarification that the Safety Set-as 
treated (SS-t) will be utilized for 
the tabulation of AEs by treatment. 
Full Analysis Set definition was 
clarified. 
Clarification that the 
Pharmacodynamic Set will be 
identified after database lock. 
To align with the current SAP. 
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Section # and Name 
Description of Change 
Brief Rationale 
10.4 Appendix 4 
Contraceptive guidance 
and collection of 
pregnancy information 
Procedure for collection of 
pregnancy information on any male 
participant’s female partner who 
becomes pregnant was added back 
in the protocol. 
Correction. 
10.14 Appendix 14: 
Management of infections 
and 
hypogammaglobulinemia 
Update of the cutoff level of serum 
total IgG for temporary 
investigational medicinal product 
(IMP) discontinuation in case of a 
hypogammaglobulinemia event.  
Correction. 
Global 
Minor administrative, consistency, 
formatting, and typographical 
changes have been made. Lists of 
abbreviations (general and tables), 
list of references, and footnotes 
have been updated in line with 
other changes made throughout the 
document. 
Updated to provide clarity and be 
consistent with remainder of 
protocol. 
 
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SERIOUS ADVERSE EVENT REPORTING 
 
Serious adverse event reporting (24h) 
Fax 
Europe and Rest of the World: +32 2 386 24 21 
Email 
Global: DS_ICT@ucb.com (for interventional clinical studies) 
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Page 10 of 116 
TABLE OF CONTENTS 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ...................................... 2 
1 
PROTOCOL SUMMARY ............................................................................................... 15 
1.1 
Synopsis ....................................................................................................................... 15 
1.2 
Schema ......................................................................................................................... 19 
1.3 
Schedule of activities ................................................................................................... 20 
1.3.1 
Additional study assessments .............................................................................. 27 
2 
INTRODUCTION ........................................................................................................... 28 
2.1 
Study rationale ............................................................................................................. 28 
2.2 
Background .................................................................................................................. 29 
2.3 
Benefit/risk assessment ................................................................................................ 30 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 31 
4 
STUDY DESIGN ............................................................................................................. 33 
4.1 
Overall design .............................................................................................................. 33 
4.2 
Scientific rationale for study design ............................................................................ 34 
4.3 
Justification for dose .................................................................................................... 34 
4.3.1 
Rationale of targeted 70% IgG reduction ............................................................ 36 
4.4 
End of study definition................................................................................................. 36 
5 
STUDY POPULATION .................................................................................................. 37 
5.1 
Inclusion criteria .......................................................................................................... 37 
5.2 
Exclusion criteria ......................................................................................................... 38 
5.3 
Lifestyle restrictions..................................................................................................... 41 
5.3.1 
Meals and dietary restrictions .............................................................................. 41 
5.3.2 
Caffeine, alcohol, and tobacco ............................................................................. 41 
5.3.3 
Activity ................................................................................................................ 41 
5.4 
Screen failures .............................................................................................................. 41 
6 
STUDY TREATMENTS ................................................................................................. 42 
6.1 
Treatments administered .............................................................................................. 42 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 43 
6.2.1 
Drug accountability ............................................................................................. 44 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 44 
6.3.1 
Procedures for maintaining and breaking the treatment blind ............................. 45 
6.3.1.1 
Maintenance of study treatment blind ....................................................... 45 
6.3.1.2 
Breaking the treatment blind in an emergency situation ........................... 46 
6.4 
Treatment compliance .................................................................................................. 46 
6.5 
Concomitant medications/treatments ........................................................................... 46 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 46 
6.5.2 
Prohibited concomitant treatments (medications and therapies) ......................... 47 
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6.5.3 
Rescue medication ............................................................................................... 48 
6.6 
Dose modification ........................................................................................................ 48 
6.7 
Criteria for study hold or dosing stoppage ................................................................... 48 
6.8 
Treatment after the end of the study ............................................................................ 48 
7 
DISCONTINUATION OF STUDY MEDICATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 48 
7.1 
Discontinuation of study medication ........................................................................... 48 
7.1.1 
Liver chemistry stopping criteria ......................................................................... 48 
7.1.2 
Other permanent discontinuation criteria ............................................................ 49 
7.1.3 
Level of follow up to be considered when permanent discontinuation from IMP 
occurs ................................................................................................................... 50 
7.1.4 
Temporary discontinuation .................................................................................. 51 
7.2 
Participant discontinuation/withdrawal from the study ............................................... 51 
7.2.1 
Study withdrawal criteria ..................................................................................... 52 
7.3 
Lost to follow-up.......................................................................................................... 53 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 53 
8.1 
Efficacy assessments .................................................................................................... 54 
8.1.1 
Brief Pain Inventory-Short Form ......................................................................... 54 
8.1.2 
Pain NRS ............................................................................................................. 54 
8.1.3 
Pressure pain threshold ........................................................................................ 55 
8.1.4 
Revised Fibromyalgia Impact Questionnaire ...................................................... 55 
8.1.5 
Fatigue NRS ......................................................................................................... 55 
8.2 
Safety assessments ....................................................................................................... 55 
8.2.1 
Physical examination ........................................................................................... 55 
8.2.2 
Neurological examination .................................................................................... 55 
8.2.3 
Vital signs ............................................................................................................ 56 
8.2.4 
Electrocardiograms .............................................................................................. 56 
8.2.5 
Clinical safety laboratory assessments ................................................................ 56 
8.2.6 
Suicidal risk monitoring ...................................................................................... 57 
8.3 
Adverse events and serious adverse events ................................................................. 57 
8.3.1 
Time period and frequency for collecting AE and SAE information .................. 57 
8.3.2 
Method of detecting AEs and SAEs .................................................................... 58 
8.3.3 
Follow-up of AEs and SAEs ................................................................................ 58 
8.3.4 
Regulatory reporting requirements for SAEs ...................................................... 58 
8.3.5 
Pregnancy ............................................................................................................ 59 
8.3.6 
Adverse events of special interest ........................................................................ 59 
8.3.7 
Adverse events of special monitoring .................................................................. 59 
8.3.8 
Anticipated serious adverse events ...................................................................... 60 
8.4 
Safety signal detection ................................................................................................. 60 
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8.5 
Treatment of overdose ................................................................................................. 61 
8.6 
Pharmacokinetics and immunogenicity ....................................................................... 61 
8.7 
Pharmacodynamics ...................................................................................................... 62 
8.8 
Genetics........................................................................................................................ 62 
8.9 
Biomarkers ................................................................................................................... 62 
8.9.1 
In vitro IgG binding assay ................................................................................... 63 
8.9.2 
Immunology ......................................................................................................... 63 
8.10 
Health economics ......................................................................................................... 63 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 63 
9.1 
Definition of analysis sets ............................................................................................ 63 
9.2 
General statistical considerations ................................................................................. 64 
9.3 
Planned efficacy/outcome analyses ............................................................................. 65 
9.3.1 
Analysis of the primary efficacy/primary endpoint ............................................. 65 
9.3.1.1 
Estimand/ICE handling rationale and impact on the study ....................... 66 
9.3.2 
Secondary efficacy analyses ................................................................................ 67 
9.3.3 
Other efficacy/other outcome analyses ................................................................ 67 
9.4 
Planned safety and other analyses................................................................................ 67 
9.4.1 
Safety analyses ..................................................................................................... 67 
9.4.2 
Other analyses ...................................................................................................... 68 
9.4.2.1 
PK analyses ............................................................................................... 68 
9.4.2.2 
Immunogenicity analyses .......................................................................... 68 
9.4.2.3 
PD analyses ............................................................................................... 68 
9.4.2.4 
Immunological analyses ............................................................................ 68 
9.5 
Handling of protocol deviations................................................................................... 68 
9.6 
Handling of dropouts or missing data .......................................................................... 69 
9.7 
Planned interim analysis and data monitoring ............................................................. 69 
9.7.1 
Interim analysis .................................................................................................... 69 
9.7.2 
Data monitoring ................................................................................................... 70 
9.8 
Determination of sample size ....................................................................................... 70 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 71 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ......................... 71 
10.1.1 
Regulatory and ethical considerations ................................................................. 71 
10.1.2 
Financial disclosure ............................................................................................. 71 
10.1.3 
Informed consent process .................................................................................... 72 
10.1.4 
Data protection ..................................................................................................... 72 
10.1.5 
Committees structure ........................................................................................... 72 
10.1.6 
Data quality assurance ......................................................................................... 73 
10.1.6.1 
Case report form completion ..................................................................... 73 
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10.1.7 
Source documents ................................................................................................ 74 
10.1.8 
Study and site closure .......................................................................................... 74 
10.1.9 
Publication policy ................................................................................................ 75 
10.2 
Appendix 2: Clinical laboratory tests .......................................................................... 76 
10.3 
Appendix 3: Adverse events – Definitions and procedures for recording, evaluating, 
follow-up, and reporting .............................................................................................. 78 
10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ......... 84 
10.5 
Appendix 5: Genetics ................................................................................................... 87 
10.6 
Appendix 6: Liver safety – suggested actions and follow-up assessments ................. 88 
10.7 
Appendix 7: Medical device AEs, adverse device effects, SAEs, and device 
deficiencies: Definition and procedures for recording, evaluating, follow-up, and 
reporting ....................................................................................................................... 91 
10.8 
Appendix 8: Rapid alert procedures ............................................................................ 92 
10.9 
Appendix 9: Country-specific requirements ................................................................ 93 
10.10 Appendix 10: Abbreviations and trademarks .............................................................. 94 
10.11 Appendix 11: Protocol amendment history ................................................................. 97 
10.11.1 
Amendment 2 (29 Nov 2022) .............................................................................. 97 
10.11.2 
Amendment 1 (24 Oct 2022) ............................................................................. 101 
10.12 Appendix 12: Assessment and Management of Tuberculosis and Tuberculosis Risk 
Factors ........................................................................................................................ 103 
10.12.1 
TB definitions .................................................................................................... 103 
10.12.2 
Screening Period ................................................................................................ 103 
10.12.3 
Physical Examination ........................................................................................ 104 
10.12.4 
Interferon gamma release assay (IGRA) ........................................................... 104 
10.12.5 
Practical steps .................................................................................................... 104 
10.12.6 
IGRA Test Conversion ...................................................................................... 107 
10.12.7 
Latent TB ........................................................................................................... 107 
10.12.8 
Active TB ........................................................................................................... 108 
10.12.9 
Safety Reporting Requirements ......................................................................... 108 
10.13 Appendix 13: Management of Adverse Event of Special Monitoring ...................... 109 
10.14 Appendix 14: Management of Infections and Hypogammaglobulinemia ................. 111 
10.15 Appendix 15: Management of Infusion Reactions or Hypersensitivity Reactions .... 112 
11 REFERENCES .............................................................................................................. 114 
SPONSOR DECLARATION ................................................................................................ 116 
 
LIST OF TABLES 
Table 1-1: 
Schedule of Activities (through Period 1) ....................................................... 20 
Table 1-2: 
Schedule of Activities (Period 2 through End of Study) ................................. 24 
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Table 1-3: 
Additional study assessments .......................................................................... 27 
Table 6-1: 
Concomitant medications prohibited during the study .................................... 47 
Table 6-2: 
Prohibited concomitant medications and therapies relative to the last 
rozanolixizumab dose ...................................................................................... 47 
Table 8-1: 
Anticipated serious adverse events for FMS population ................................. 60 
Table 10-1: 
Highly effective contraceptive methodsa ......................................................... 85 
Table 10-2: 
Phase 2 liver chemistry stopping criteria and follow-up assessments ............. 88 
Table 10-3: 
Phase 2 liver chemistry increased monitoring criterion with continued 
study medication .............................................................................................. 90 
Table 10-4: 
Suggested management guidelines at site for infusion reactions or 
anaphylaxis .................................................................................................... 112 
 
LIST OF FIGURES 
Figure 1-1: 
Study Schematic............................................................................................... 19 
Figure 7-1: 
Liver Chemistry Stopping Criteria and Increased Monitoring Algorithm ....... 49 
Figure 10-1: 
Decision tree for IGRA TB results at Screening or before entering a study . 105 
Figure 10-2: 
Decision tree for IGRA TB results during a study ........................................ 106 
 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title: A randomized, double-blind, placebo-controlled, multicenter, Phase 2a, proof-of-
concept study to evaluate the efficacy and safety of rozanolixizumab to treat adult study 
participants with severe fibromyalgia syndrome 
Short title: A Phase 2a proof-of-concept study to evaluate the efficacy and safety of 
rozanolixizumab to treat adult study participants with severe fibromyalgia syndrome 
Rationale: Recently there is increasing scientific evidence in the pathobiology of severe 
fibromyalgia syndrome (FMS) suggesting it may be an autoimmune condition that is mediated 
by immunoglobulin (Ig)G. Research has shown that the transfer of IgG from patients with severe 
FMS, but not IgG from healthy volunteers, to rodents transfers the clinical features of severe 
FMS (Goebel et al, 2021). Features transferred included allodynia, thermal hypersensitivity, 
reduced grip strength, and small fiber neuropathy. IgG derived from patients with severe FMS 
was also found to bind cells in the dorsal root ganglia (DRG) in rodents as well as to cells in 
human DRG sections. These findings suggest that there are pathogenic IgG present in patients 
with severe FMS that contribute to their clinical symptoms. These novel scientific insights 
support the hypothesis that the reduction of IgG in patients with severe FMS is a potential 
therapeutic treatment approach. The aim of this study is to reduce IgG levels in patients with 
severe FMS with rozanolixizumab and assess its safety and efficacy in these patients. 
Objectives and endpoints 
Objectives 
Endpoints/Estimands 
Primary 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
Primary estimand (efficacy): 
• Treatment: rozanolixizumab 560mg once 
weekly (QW) or Placebo QW 
• Target Population: study participants with 
severe FMS 
• Endpoint: Brief Pain Inventory-short form 
(BPI-SF) average interference score after 
12 weeks of double-blind treatment. 
• Intercurrent event (ICE) handling: 
− The ICE discontinuation of treatment 
will be handled using a hypothetical 
strategy assuming that the study 
participants did not experience the 
events, with data following 
discontinuation excluded from 
analysis. 
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Objectives 
Endpoints/Estimands 
• Population level summary: mean 
difference in average BPI-SF interference 
score between the two treatments 
Secondary 
• To assess the safety and tolerability of 
rozanolixizumab in study participants 
with severe FMS 
• Occurrence of treatment-emergent adverse 
events (TEAEs) during the study 
• TEAEs leading to withdrawal of 
investigational medicinal product (IMP) 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
• BPI-SF average interference score after 
24 weeks of treatment 
• Revised Fibromyalgia Impact 
Questionnaire (FIQR) score after 
10 weeks of treatment 
• Mean 7-day average daily pain score 
(Pain numeric rating scale [NRS]) after 
10 weeks of treatment 
• Mean 7-day fatigue score (Fatigue NRS) 
after 10 weeks of treatment  
Exploratory 
• To assess the pharmacokinetics (PK) of 
rozanolixizumab in study participants 
with severe FMS 
• Plasma concentration of rozanolixizumab 
prior to dosing on Week 13 and Week 25 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
• Pressure pain threshold as measured by 
pressure algesiometry 
• To assess the safety and tolerability of 
rozanolixizumab in study participants 
with severe FMS 
• Change from Baseline in vital signs and 
laboratory results at scheduled 
assessments during the Treatment Period 
through the Run-out Period 
• To evaluate the incidence and emergence 
of antidrug antibody (ADA) of 
rozanolixizumab in study participants 
with severe FMS 
• Antidrug antibody incidence at scheduled 
assessments during the Treatment Period 
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Objectives 
Endpoints/Estimands 
• To assess the pharmacodynamic (PD) 
effect of rozanolixizumab in study 
participants with severe FMS 
• Value (absolute) and change from 
Baseline (absolute and percentage) in 
serum total IgG and IgG subclasses at 
scheduled assessments during the 
Treatment Period 
• To assess the effect of rozanolixizumab 
on exploratory biomarkers in study 
participants with severe FMS 
• Assessment of IgG binding in in vitro cell 
assay at scheduled assessments during the 
Treatment Period and the Run-out Period 
• Assess genetic variation for potential 
effects on disease progression and/or drug 
response and also any changes in 
epigenetics 
• Exploratory biomarkers may be measured 
to evaluate changes from Baseline in 
response to rozanolixizumab 
Overall design 
This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, proof-of-concept 
study to evaluate the efficacy, safety, PK, and PD of rozanolixizumab for the treatment of severe 
FMS. The primary endpoint is the average BPI-SF interference score after 12 weeks of double-
blind treatment. 
The study will consist of Screening Period of up to 28 days, a 2-week, single-blind Run-in 
Period, 2 subsequent 12-week, double-blind Treatment Periods, followed by a 2-week, single-
blind Run-out Period, and a 5-week Safety Follow-Up (SFU) Period. 
Study participants will be randomized in a 1:1:1 ratio to 1 of 3 sequences. The study participants 
in each sequence will receive the following treatment regimen during the double-blind Treatment 
Periods (see Figure 1-1): 
• Sequence 1: Rozanolixizumab 560mg subcutaneously (sc) QW for 24 weeks (12 + 12 weeks 
Treatment Period) (N=20, Group 1) 
• Sequence 2: Placebo sc QW for 12 weeks, followed by rozanolixizumab 560mg sc QW for 
12 weeks (N=20, Group 2) 
• Sequence 3: Placebo sc QW for 24 weeks (N=20, Group 3) 
The initial 2-week Run-in Period and the final 2-week Run-out Period will be study participant-
blind, with study participants not informed that they are receiving placebo, to limit the impact of 
any start-of-study or end-of-study induced placebo effects. The two 12-week Treatment Periods 
will be study participant-, investigator-, and sponsor-blind. It is important that study participants 
do not know when their treatment changes, whether it is going from Run-in to Period 1, Period 1 
to Period 2, or Period 2 to Run-out. 
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After approximatively 30 study participants have been randomized and these study participants 
have completed their 2 double-blind Treatment Periods, an interim analysis may be conducted 
with the possibility of stopping for efficacy or futility. 
An internal Safety Monitoring Committee (SMC) will regularly review (approximately every 
3 months, with the option to adapt the frequency based on recruitment rates) the available 
blinded safety data. 
In addition, a Program Independent data monitoring committee (PiDMC) is in place to evaluate 
data over the entire rozanolixizumab clinical development program as this molecule is being 
investigated in several indications.  
Number of study participants 
In total and allowing for a dropout rate of 25%, approximately 60 study participants are planned 
to be enrolled and randomized in the study at up to 8 centers from the UK, with a target of 
48 evaluable study participants completing the study. Evaluable study participants are those with 
BPI-SF scores at Baseline, Visit 15, and Visit 27 (see also Section 9.3). 
Treatment groups and duration 
The maximum study duration per study participant will be 37 weeks. 
• Screening Period: Eligibility will be assessed during the Screening Period of up to 28 days. 
• Run-in Period: Study participants who have been confirmed eligible to participate in the 
study will be randomized 1:1:1 to receive rozanolixizumab 560mg sc QW or placebo sc QW, 
as described in the study design section above. During the 2-week Run-in Period, all study 
participants will receive placebo sc QW and will be blinded to this treatment. 
• Treatment Period: As shown in Section 1.2, study participants will receive rozanolixizumab 
560mg sc QW for two 12-week Treatment Periods, placebo sc QW for the first 12-week 
Treatment Period followed by rozanolixizumab 560mg sc QW for the second 12-week 
Treatment Period, or placebo sc QW for two 12-week Treatment Periods. 
• Run-out Period: At the end of both 12-week Treatment Periods, all study participants will 
receive placebo sc QW during a 2-week Run-out Period and will be blinded to this treatment. 
• Safety Follow-up Period: Study participants who complete both Treatment Periods and 
Run-out Period will  enter the 5-week SFU Period. These participants will attend the EOT 
visit 2 weeks after the last dose in the Run-out Period and the SFU/EOS visit 4 weeks later (6 
weeks after the last dose in the Run-out Period). Study participants who permanently 
discontinue IMP are encouraged to complete the EOT/EW Visit and the SFU/End of Study 
(EOS) Visit. 
 
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1.2 
Schema 
Figure 1-1: Study Schematic 
 
EOS=end of study; QW=once weekly; sc=subcutaneous. 
Note: All study participants receive placebo in a single-blind manner during the Run-in and Run-out Periods. 
 
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1.3 
Schedule of activities 
The Schedules of Activities are provided in Table 1-1 (through Treatment Period 1) and in Table 1-2 (Treatment Period 2 through 
EOS). Additional study assessments are outlined in Section 1.3.1. 
Table 1-1: 
Schedule of Activities (through Period 1) 
Procedure 
Screen 
Run-in 
Run-in 
12-week Treatment Period: 1 
Visit number 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Visit window 
up to 28 
days 
- 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
Week  
-6 
-2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Day 
-42 
-14 
-7 
1 
8 
15 
22 
29 
36 
43 
50 
57 
64 
71 
78 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Verification of inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
General medical/ procedure history 
(including headache history and pain 
management program)a 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C-SSRSb 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
X 
 
X 
 
  
 
X 
 
  
 
X 
 
  
 
Serology (Hepatitis B, Hepatitis C, and 
HIV) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IGRA TB test (optional)c 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory assessments (full 
hematology, chemistry, urinalysis) 
X 
X 
 
X 
 
 
 
X 
 
 
  
X 
 
 
 
Urine drug screend 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 1-1: 
Schedule of Activities (through Period 1) 
Procedure 
Screen 
Run-in 
Run-in 
12-week Treatment Period: 1 
Visit number 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Visit window 
up to 28 
days 
- 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
Week  
-6 
-2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Day 
-42 
-14 
-7 
1 
8 
15 
22 
29 
36 
43 
50 
57 
64 
71 
78 
12-lead ECGe 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (blood pressure, pulse, and 
temperature)f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Full physical examinationg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brief physical examinationg 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Full neurological examinationh 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain NRS 
Xi 
Xi 
Xi 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xi 
Xi 
BPI-SF 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
FIQR  
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Fatigue NRS 
Xj 
Xi 
Xi 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xi 
Xi 
Pressure pain thresholdk 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
IMP discontinuation/study withdrawal 
criteria 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication review 
Xl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMP administration 
 
X(pb) 
X(pb) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PKm 
 
X 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
ADAm 
 
X 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
IgG (total, subclasses) m 
Xn 
X 
 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
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Table 1-1: 
Schedule of Activities (through Period 1) 
Procedure 
Screen 
Run-in 
Run-in 
12-week Treatment Period: 1 
Visit number 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Visit window 
up to 28 
days 
- 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
Week  
-6 
-2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Day 
-42 
-14 
-7 
1 
8 
15 
22 
29 
36 
43 
50 
57 
64 
71 
78 
IgG binding, in vitro assay 
 
 
 
Xo 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for DNA and RNA 
analysis 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum complement (C3, C4) and 
plasma complement (C3a, C5a)pq 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Exploratory biomarkers 
 
Xm,q 
 
Xm,q 
 
 
 
 
 
 
 
 
 
 
 
ADA=anti-rozanolixizumab antibodies; BPI-SF=brief pain inventory-short form; C-SSRS=Columbia Suicidality Severity Rating Scale; d=day; 
ECG=electrocardiogram; FIQR=Revised Fibromyalgia Impact Questionnaire; HBV=Hepatitis B virus; HIV=Human Immunodeficiency Virus; 
Ig=immunoglobulin; IGRA=interferon gamma release assay; IMP=investigational medicinal product; NRS=numeric rating scale; pb=placebo; 
PK=pharmacokinetics; PRN=pro re nata; TB=tuberculosis 
Note: Assessments in the weekly columns are meant to be performed at the start of that Week prior to dosing, unless otherwise specified. 
Note: The BPI-SF should be completed by the study participants in a quiet place prior to other patient-reported outcomes or protocol-specified assessments at 
each visit. 
Note: The Baseline for each variable will be taken as the value measured prior to, but closest to, the treatment on Day 1. This may be measured on Day 1 prior 
to treatment or during Weeks -1 or ‑2 depending on the endpoint. 
a History of the completion of a pain management program should be collected when available. 
b A full C-SSRS assessment will be performed only when the study participant has a positive response to the suicidal ideation query. If a study participant has 
active suicidal ideation as confirmed by the answer ‘Yes’ to Question 4 or Question 5 of the C-SSRS assessments, the study participant will be excluded or 
withdrawn from the study and immediately referred to a mental healthcare professional. A C-SSRS assessment may be conducted at other visits at the 
discretion of the investigator. 
c The IGRA test is optional and may be performed at the investigator’s discretion, based on an individual risk assessment for the study participant, including, 
but not limited to, the following considerations: medical history, potential prior exposure to other individuals with known TB, local prevalence of TB, 
clinical practice, and applicable local guidelines. Management of an IGRA test result will be done as outlined in Section 10.12. 
d Urine drug screen for drug abuse includes amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, and opiates. This test can be performed at 
other visits at the discretion of the investigator.  
e 12-lead ECG can be performed any time during the study at the investigator’s discretion. 
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Table 1-1: 
Schedule of Activities (through Period 1) 
Procedure 
Screen 
Run-in 
Run-in 
12-week Treatment Period: 1 
Visit number 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Visit window 
up to 28 
days 
- 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
Week  
-6 
-2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Day 
-42 
-14 
-7 
1 
8 
15 
22 
29 
36 
43 
50 
57 
64 
71 
78 
f Vital signs comprise systolic and diastolic blood pressure, pulse rate, and temperature. At Visit 1, 2, 3, and 4, vital signs will be measured prior to IMP 
administration, at the end of the infusion (+5 min), and at 2 hours after the end of infusion (±15 min). At Visit 5, 6, and 7, vital signs will be measured prior 
to IMP administration and 1 hour after the end of infusion (±15 min). From Visit 8 through Visit 14, the vital signs will be measured approximately 
15 minutes prior to IMP administration. At Screening, vital signs will be taken only once during the visit. 
g A brief physical examination can also be performed on the occurrence of an adverse event. Brief and full physical examinations should include evaluation 
for medical history, for signs and symptoms of latent or active TB, and for risk factors for exposure to TB. An IGRA test can be performed any time, at the 
investigator’s discretion. 
h A full neurological examination should also be performed for any study participant who experiences severe and/or serious headache and for study 
participants who experience suspected aseptic meningitis. For details of the assessments included in these examinations see Section 8.2.1 (description of full 
and brief physical examination), and Section 8.2.2 (description of full and brief neurological examination). 
i Daily 24-hr pain and fatigue assessments to be collected every day for a week. Within the Screening Period, the daily average pain over the previous 
24 hours will be captured using the Pain NRS through a diary over a 10-day period. Study participants require a minimum of 7 out of the 10 daily Pain NRS 
assessments over this 10-day period  to be eligible for randomization. 
j The 24-hr pain and fatigue assessments to be collected for that day only. 
k To be performed before IMP dosing. 
l Study participants to provide their usual range doses of analgesics PRN. 
m On dosing days, PK, ADA, and IgG will be taken pre-dose. 
n Total IgG only. 
o 80mL at Visit 3. 
p Samples for serum complement (C3, C4) and plasma complement (C3a, C5a) are collected predose at Visit 3 (Day 1) for all study participants. In study 
participants who experience an infusion reaction or hypersensitivity reaction at site, samples should also be taken 2 hours and 4 hours after the onset of the 
event, or otherwise as soon as possible but prior to the next dose. 
q 10mL at Visit 1 and Visit 3. In study participants who experience severe and/or serious headaches or suspected aseptic meningitis, exploratory biomarker 
samples should also be taken 4 hours after the onset of the event, or otherwise as soon as possible within 72 hours after the onset of the event. 
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Table 1-2: 
Schedule of Activities (Period 2 through End of Study) 
Procedure 
12-week Treatment Period: 2 
Run-out 
Run-out 
EOT/ 
EW 
SFU/ 
EOS 
Visit number 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
- 
- 
Visit window 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
±7d 
Week 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
28 
32 
Day 
85 
92 
99 
106 
113 
120 
127 
134 
141 
148 
155 
162 
169 
176 
190 
218 
C-SSRSa 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
Urine pregnancy test 
X 
 
  
 
X 
 
  
 
X 
 
  
 
X 
 
X 
X 
Laboratory assessments 
(full hematology, chemistry, 
urinalysis) 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
 
Vital signs (blood pressure, 
pulse and temperature at 
every visit)b 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Full physical examinationc  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Brief physical examinationc 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Full neurological 
examinationd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Pain NRS 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xf 
Xf 
Xf 
 
Xe 
Xe 
BPI-SF 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
FIQR  
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X  
X 
Fatigue NRS 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xf 
Xf 
Xf 
 
Xe 
Xe 
Pressure pain thresholdg 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X  
X  
IMP discontinuation/study 
withdrawal criteria 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse event review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Table 1-2: 
Schedule of Activities (Period 2 through End of Study) 
Procedure 
12-week Treatment Period: 2 
Run-out 
Run-out 
EOT/ 
EW 
SFU/ 
EOS 
Visit number 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
- 
- 
Visit window 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
±7d 
Week 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
28 
32 
Day 
85 
92 
99 
106 
113 
120 
127 
134 
141 
148 
155 
162 
169 
176 
190 
218 
Concomitant medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMP administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X(pb) 
X(pb) 
 
 
PKh 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
ADAh 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
X 
X 
IgG (total, subclasses)h 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
IgG binding, in vitro assayh,i 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Blood sampling for DNA 
and RNA analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Exploratory biomarkers 
Xf,g 
 
 
 
 
 
 
 
 
 
 
 
Xf,g 
 
 
Xg 
ADA=anti-rozanolixizumab antibodies; BPI-SF=brief pain inventory-short form; C-SSRS=Columbia Suicidality Severity Rating Scale; d=day; EOS=End of 
Study; EOT=End of Treatment; EW=Early Withdrawal; FIQR=Revised Fibromyalgia Impact Questionnaire; Ig=immunoglobulin; IGRA=interferon gamma 
release assay; IMP=investigational medicinal product; NRS=numeric rating scale; pb=placebo; PK=pharmacokinetics; SFU=Safety Follow-up; 
TB=tuberculosis 
Note: Assessments in the weekly columns are meant to be performed at the start of that Week prior to dosing, unless otherwise specified. 
Note: The BPI-SF should be completed by the study participants in a quiet place prior to other patient-reported outcomes or protocol-specified assessments at 
each visit. 
a A full C-SSRS assessment will be performed only when the study participant has a positive response to the suicidal ideation query. If a study participant has 
active suicidal ideation as confirmed by the answer ‘Yes’ to Question 4 or Question 5 of the C-SSRS assessments, the study participant will be excluded or 
withdrawn from the study and immediately referred to a mental healthcare professional. A C-SSRS assessment may be conducted at other visits at the 
discretion of the investigator. 
b Vital signs comprise systolic and diastolic BP, pulse rate, and temperature. At Visit 15 and Visit 16, vital signs will be measured prior to IMP administration, 
at the end of the infusion (+5 min) and at 2 hours after the end of infusion ( ±15 min). At Visit 17, 18, and 19, vital signs will be measured prior to IMP 
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Table 1-2: 
Schedule of Activities (Period 2 through End of Study) 
Procedure 
12-week Treatment Period: 2 
Run-out 
Run-out 
EOT/ 
EW 
SFU/ 
EOS 
Visit number 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
- 
- 
Visit window 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
±7d 
Week 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
28 
32 
Day 
85 
92 
99 
106 
113 
120 
127 
134 
141 
148 
155 
162 
169 
176 
190 
218 
administration and 1 hour after the end of infusion (±15 min). From Visit 20 through Visit 28, the vital signs will be measured approximately 15 minutes 
prior to IMP administration. At EOT/EW and SFU/EOS Visits, vital signs will be taken only once during the visit. 
c A brief physical examination can also be performed on the occurrence of an adverse event. Brief and full physical examinations should include evaluation 
for medical history, for signs and symptoms of latent or active TB, and for risk factors for exposure to TB. An IGRA test can be performed any time, at the 
investigator’s discretion. 
d In addition to the EOT/EW and SFU/EOS Visits, a full neurological examination should be performed for any study participant who experiences severe 
and/or serious headache and/or suspected aseptic meningitis (see Section 10.13). 
e The 24-hr pain and fatigue assessments to be collected for that day only. 
f Daily 24-hr pain and fatigue assessments to be collected every day for a week. 
g To be performed before IMP dosing. 
h On dosing days, PK, ADA, IgG will be taken pre-dose. 
i 10mL at Visit 15, 27, and SFU/EOS. 
 
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1.3.1 
Additional study assessments 
In addition to those detailed in Table 1-1 and Table 1-2, the assessments in Table 1-3 may be 
required in case of adverse events of special monitoring (AESMs) (severe and/or serious 
headache and suspected aseptic meningitis, see Section 8.3.7). Note that additional vital sign 
measurements and/or additional investigations may be taken at the discretion of the investigator. 
Table 1-3: 
Additional study assessments 
Assessment 
When applicable 
For study participants who experience a severe and/or serious headachea and for study 
participants with suspected aseptic meningitis: 
Headache or 
Suspected 
aseptic 
meningitis 
follow-up 
questionnaire 
Headache follow-up questionnaire which sites will receive after reporting AESM of 
severe and/or serious headache should be completed promptly and returned to the 
Sponsor via the SAE reporting process. 
Suspected aseptic meningitis follow-up questionnaire which sites will receive after 
reporting AESM of suspected aseptic meningitis should be completed promptly and 
returned to the Sponsor via the SAE reporting process. 
Full 
neurological 
examination 
In study participants who report severe and/or serious headache or with suspected 
aseptic meningitis at the clinic visit, a full neurological examination (including 
fundoscopy) should be performed (see Section 10.13). In study participants who 
report a severe and/or serious headache or features suggestive of aseptic meningitis 
while at home, a visit to the site for the full neurological examination should be 
arranged for as soon as is practically possible. 
Blood analysis 
Blood sample collection for exploratory analysis. 
Other 
In study participants who report severe and/or serious headache, other diagnostic 
procedures including, but not limited to, CT scan, MRI and/or LP for CSF collection 
are to be performed if indicated at the discretion of the investigator. 
For study participants who experience suspected aseptic meningitis: 
Lumbar 
puncture 
In study participants who reported signs and/or symptoms of meningitis which 
required a lumbar puncture, results of the CSF analysis should be recorded and 
preliminary data should be included on the SAE form used for reporting the event as 
an AESM within 24 hours (ie, preliminary data reported on the first reporting may not 
have CSF results yet but the reporting should occur as soon as there is a suspected 
diagnosis. Full results should be communicated in subsequent exchanges with UCB). 
Additional 
analysis 
Results of all investigations should be recorded and preliminary data should be 
included on the SAE form used for reporting the event as an AESM. 
Please include details on all investigations results including but not limited to blood 
or CSF cultures and analysis/ PCR test (including list of microorganisms tested) / 
MRI scans +/- gadolinium. 
AESM=adverse event under special monitoring; CSF=cerebrospinal fluid; CT=computed tomography; 
eCRF=electronic case report form; LP=lumbar puncture; MRI=magnetic resonance imaging; PCR=polymerase 
chain reaction; SAE=serious adverse event 
a For these assessments, the term headache includes migraine. 
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The frequency of the collection of samples for exploratory biomarker sample collection after 
severe and/or serious headache or suspected aseptic meningitis are described in Section 1.3. 
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 pathogenic 
autoantibodies. The aim is to reduce the concentration of pathogenic IgG in patients with 
autoimmune diseases mediated by the action of IgG autoantibodies. 
The FcRn recycles IgG and albumin and transports it bidirectionally across epithelial barriers. 
Recent studies have shown that FcRn rescues both IgG and albumin from intracellular lysosomal 
degradation by recycling it from the sorting endosome to the cell surface (Roopenian and 
Akilesh, 2007). Neonatal Fc receptor may also mediate transcytosis of IgG to facilitate its 
distribution within tissues. Rozanolixizumab has been specifically designed to block IgG binding 
to FcRn without blocking the binding and recycling of albumin. 
Production of pathogenic IgG autoantibodies is the major pathophysiology leading to a number 
of autoimmune diseases, which include myasthenia gravis (MG), pemphigus vulgaris (PV), 
immune thrombocytopenia (ITP), Goodpasture’s syndrome, neuromyelitis optica, and Guillain-
Barré Syndrome. Recently there is increasing scientific evidence regarding the pathobiology of 
FMS that suggests it may also be an IgG-mediated condition, as detailed in Section 2.1. 
Therefore, the removal of IgG by FcRn blockade may provide an effective therapeutic option for 
FMS. 
Nonclinical and clinical data generated on rozanolixizumab support the sc administration of 
rozanolixizumab in study participants with IgG autoantibody-mediated conditions, including 
primary ITP and generalized MG (ie, gMG). Recently, a Phase 3 UCB study in patients with 
gMG met all primary and secondary endpoints with statistical significance and showed 
rozanolixizumab was well tolerated with no new safety concerns. Overall, data from the 
rozanolixizumab clinical development program showed that repeated administrations of 
rozanolixizumab at a dose approximating 7mg/kg and 10mg/kg sc are generally well tolerated, 
with an acceptable safety profile in completed studies. The TEAEs were most frequently 
reported in the SOC of nervous system disorders. The most frequently reported TEAEs in 
rozanolixizumab-treated study participants in MG0003, a completed phase 3 study evaluating the 
efficacy and safety of rozanolixizumab in patients with gMG and upon repeated cyclic treatment 
were headache, diarrhoea, pyrexia, nausea, and arthralgia. Therefore, rozanolixizumab represents 
an innovative, subcutaneous anti-FcRn monoclonal antibody that may provide a novel and 
specific therapeutic approach for the treatment of patients with severe FMS. 
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). 
2.1 
Study rationale 
Recently there is increasing scientific evidence suggesting severe FMS may be an autoimmune 
condition that is mediated by IgG. A consortium of UK and Swedish investigators has reported 
research findings indicating that serum IgG contributes to the pathogenesis of severe FMS 
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(Goebel et al, 2021). The team transferred both single and pooled serum IgG from patients with 
severe FMS to rodents and identified typical features of clinical FMS in the rodents, including 
allodynia, thermal hypersensitivity, reduced grip strength, and small fiber pathology when 
compared with the transfer of serum IgG from healthy volunteers (Goebel et al, 2021). IgG 
derived from patients with severe FMS was also found to bind cells in the DRG in rodents as 
well as to cells in human DRG sections. These findings suggest that there are pathogenic IgG 
present in patients with severe FMS that contribute to their clinical symptoms. Recently, 
additional research quantified anti-satellite glia cells (SGCs) IgG levels using an indirect 
immunofluorescence murine cell culture assay, showed elevated anti-SGC IgG levels in 
fibromyalgia cohorts compared with control group, and suggested elevated anti-SGC IgG was 
associated with higher levels of self-reported pain (Krock et al, 2023). 
These novel scientific insights support the hypothesis that the reduction of IgG in patients with 
severe FMS is a potential therapeutic treatment approach. The aim of this study is to reduce IgG 
levels in patients with severe FMS with rozanolixizumab and assess its safety and efficacy in 
these patients. 
2.2 
Background 
Fibromyalgia is a highly prevalent (2 to 3% of adult population) and complex syndrome 
primarily characterized by the presence of chronic widespread pain, but which also incorporates 
a wide range of other symptoms adversely impacting on function and quality of life such as 
severe fatigue, cognitive dysfunction, and sleep disturbances (Häuser et al, 2015). This can 
impair working ability, leading to reduced productivity and high healthcare costs (White et al, 
2008). The direct and indirect costs related to FMS are higher among patients with more severe 
disease (Chandran et al, 2012). 
Pain throughout the body is generally considered the most debilitating of the symptoms 
experienced by patients with fibromyalgia (Mease et al, 2011). The scales used to measure and 
monitor pain levels vary and include visual analog scales (VAS) for pain, the McGill Pain 
Questionnaire, the Fibromyalgia Impact Questionnaire pain item, various numerical rating scales 
(often recorded in diaries), and the BPI-SF. The BPI-SF interference score measures the impact 
of pain across seven domains of daily life experience and was considered as being suitable for 
measuring the effect of a treatment that may improve the experience of pain and the functional 
interference experienced by patients. 
Challenges surround the diagnosis of FMS as there is no confirmatory laboratory test, and, 
consequently, it often takes >2 years for patients to obtain a diagnosis, often involving multiple 
consultations with different physicians. An absence of specific disease biomarkers also hinders 
patient stratification and impacts on all areas of research into FMS. Current clinical practice 
recommendations and guidelines for FMS include non-pharmacologic and pharmacologic 
strategies, with focus towards reduction of symptoms and improvement of function. 
Pharmacological agents include tricyclic antidepressants, anti-epileptic drugs, selective serotonin 
reuptake inhibitors, and norepinephrine/serotonin reuptake inhibitors. While the US Food and 
Drug Administration has approved pregabalin, duloxetine, and milnacipran for treatment of 
fibromyalgia in adults, the modest efficacy of available therapies in many patients underlines the 
unmet clinical need for this patient population. Severe patients are distinguished by their higher 
scores on pain and other scales, as well as significant differences in disability and depression 
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(Chandran et al, 2012). Patients with severe FMS have an unmet need due to the limited 
efficacious treatment options available. 
2.3 
Benefit/risk assessment 
Though available drug and non-drug treatments can reduce FMS symptoms and their impact on a 
patient’s life, the modest efficacy of these therapies in most patients leaves a significant unmet 
clinical need (Macfarlane et al, 2017; Mascarenhas et al, 2021), particularly in the clinical setting 
of severe FMS. Novel scientific insights support the hypothesis that the reduction of IgG in 
patients with severe FMS is a potential therapeutic treatment approach. In removal of IgG 
autoantibodies by FcRn blockade and preventing their functional consequences, rozanolixizumab 
has the potential to alleviate the signs and symptoms of severe FMS that are not adequately 
addressed by available standard of care (SoC) treatments. The potential for this effective 
treatment approach could result in meaningful improvements to quality of life, reduction in long-
term disability, and decreased utilization of concomitant medication (eg, gabapentinoids, 
nonsteroidal anti-inflammatory drugs, opioids, paracetamol, antiepileptics) in this patient 
population. 
The aim of this study is to reduce IgG levels in patients with severe FMS with rozanolixizumab, 
given the recent evidence that severe FMS may be an autoimmune condition that is mediated by 
IgG. A rozanolixizumab-induced IgG lowering of about 70% from Baseline is similar to that 
achieved with other FcRn antagonists and alternative strategies such as plasma exchange 
(PLEX), and falls within the range associated with clinical benefit in various autoimmune 
indications. For FMS, indication-specific targets for IgG lowering are not yet established; 
however, the current assumption is that the desired level of IgG reduction would be similar to 
gMG and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (~70%) (see 
Section 4.3.1) and of clinical benefit to patients with FMS. 
Rozanolixizumab represents an innovative, anti-FcRn monoclonal antibody that may provide a 
novel and specific therapeutic approach for the treatment of patients with severe FMS. While not 
previously evaluated in severe FMS, data show that rozanolixizumab markedly lowers serum 
IgG and IgG autoantibody levels in patients with gMG. 
In MG0003, a Phase 3 study evaluating efficacy and safety of sc rozanolixizumab in adult 
patients with gMG 
 clinical efficacy of rozanolixizumab was demonstrated by 
improvements vs placebo in all efficacy endpoints tested in the study. There were clinically 
meaningful and statistically significant reductions from baseline in the primary endpoint, MG 
activities of daily living (ADL) score, at Day 43 for both rozanolixizumab dose groups versus 
placebo. 
The identified adverse drug reactions associated with sc administration of rozanolixizumab are 
headaches, diarrhoea, pyrexia, nausea, upper respiratory tract infections, arthralgia, rash, 
injection site reactions, vomiting, myalgia, and herpes simplex infections. 
Headache is the most commonly reported ADR, and these were mostly mild to moderate and 
easily managed with over-the-counter medications. Important potential risks are serious 
hypersensitivity reactions and serious infections. Other safety topics of interest include effects on 
vaccination response, effects on the kidney, reductions in albumin and plasma proteins, 
drug-induced aseptic meningitis, and decreased platelet counts. These risks can be mitigated by 
careful monitoring, exclusion of at-risk study participants, and appropriate protocol withdrawal 
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and stopping criteria. Additionally, protocol guidance for management of 
hypogammaglobulinemia/infection and infusion and hypersensitivity reactions is provided in 
Appendix 14 (Section 10.14) and Appendix 15 (Section 10.15), respectively. The management of 
and expedited reporting requirements of the AESMs (severe and/or serious headaches and 
suspected aseptic meningitis) to UCB are specified in Appendix 13 (Section 10.13). 
Restrictions on use of live vaccines have been defined in the exclusion criterion 25a. If 
vaccination with non-live vaccines (including coronavirus disease 2019 [COVID-19] vaccines) is 
considered necessary once a study participant has started therapy with IMP, then the degree of 
protection afforded with a vaccine may be compromised while the participant is being treated 
with IMP. 
Given the clinical evidence to date, the overall risk to the participants in this study is deemed to 
be low and the benefit‑risk balance for study participants is anticipated to be favorable. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of rozanolixizumab may be found in the current version of the IB. 
3 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints/Estimands 
Primary 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
Primary estimand (efficacy): 
• Treatment: rozanolixizumab 560mg QW 
or Placebo QW 
• Target Population: study participants with 
severe FMS 
• Endpoint: BPI-SF average interference 
score after 12 weeks of double-blind 
treatment. 
• Intercurrent event handling: 
− The ICE discontinuation of treatment 
will be handled using a hypothetical 
strategy assuming that the study 
participants did not experience the 
events, with data following 
discontinuation excluded from 
analysis. 
• Population level summary: mean 
difference in average BPI-SF interference 
score between the two treatments 
Secondary 
• To assess the safety and tolerability of 
rozanolixizumab in study participants 
with severe FMS 
• Occurrence of TEAEs during the study 
• TEAEs leading to withdrawal of IMP 
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Objectives 
Endpoints/Estimands 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
• BPI-SF average interference score after 
24 weeks of treatment 
• FIQR score after 10 weeks of treatment 
• Mean 7-day average daily pain score 
(Pain NRS) after 10 weeks of treatment 
• Mean 7-day fatigue score (Fatigue NRS) 
after 10 weeks of treatment 
Exploratory 
• To assess the PK of rozanolixizumab in 
study participants with severe FMS 
• Plasma concentration of rozanolixizumab 
prior to dosing on Week 13 and Week 25 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
• Pressure pain threshold as measured by 
pressure algesiometry 
• To assess the safety and tolerability of 
rozanolixizumab in study participants 
with severe FMS 
• Change from Baseline in vital signs and 
laboratory results at scheduled 
assessments during the Treatment Period 
through the Run-out Period 
• To evaluate the incidence and emergence 
of ADA of rozanolixizumab in study 
participants with severe FMS 
• Antidrug antibody incidence at scheduled 
assessments during the Treatment Period 
• To assess the PD effect of 
rozanolixizumab in study participants 
with severe FMS 
• Value (absolute) and change from 
Baseline (absolute and percentage) in 
serum total IgG and IgG subclasses at 
scheduled assessments during the 
Treatment Period 
• To assess the effect of rozanolixizumab 
on exploratory biomarkers in study 
participants with severe FMS 
• Assessment of IgG binding in in vitro cell 
assay at scheduled assessments during the 
Treatment Period and the Run-out Period 
• Assess genetic variation for potential 
effects on disease progression and/or drug 
response and also any changes in 
epigenetics 
• Exploratory biomarkers may be measured 
to evaluate changes from Baseline in 
response to rozanolixizumab 
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4 
STUDY DESIGN 
4.1 
Overall design 
This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, proof-of-concept 
study to evaluate the efficacy, safety, PK, and PD of rozanolixizumab for the treatment of severe 
FMS. Study participants who have a confirmed diagnosis of FMS, with pain intensity ≥6 and 
<10 on Pain NRS and a BPI-SF interference score ≥6 will be enrolled into the study. 
In total and allowing for a dropout rate of 25%, approximately 60 study participants are planned 
to be enrolled and randomized in the study at up to 8 centers from the UK, with a target of 
48 study participants completing the study. 
The study will consist of a 28-day Screening Period, a 2-week, single-blind Run-in Period, 
2 subsequent 12-week, double-blind Treatment Periods, followed by a 2-week, single-blind Run-
out Period and a 5-week SFU Period. 
Study participants will be randomized in a 1:1:1 ratio to 1 of 3 sequences. The study participants 
in each sequence will receive the following treatment regimen during the double-blind Treatment 
Periods (see Figure 1-1): 
• Sequence 1: Rozanolixizumab 560mg sc QW for 24 weeks (12 + 12 weeks Treatment 
Period) (N=20, Group 1) 
• Sequence 2: Placebo sc QW for 12 weeks, followed by rozanolixizumab 560mg sc QW for 
12 weeks (N=20, Group 2) 
• Sequence 3: Placebo sc QW for 24 weeks (N=20, Group 3). 
The two 12-week period design allows for both intra- and inter-study participant comparisons. 
Sequence 2 allows for intra-study participant comparison of 12 weeks receiving placebo and 
12 weeks receiving rozanolixizumab. Sequence 3, which has placebo throughout, enables 
adjustments for any period effects, and Sequence 1 Period 1 allows for inter-study participant 
comparisons with both Sequence 2 (Period 1) and Sequence 3 (Period 1 and Period 2). 
In addition, comparing treatment effects after 24 weeks of treatment is possible through 
comparing the 24-week assessments from Sequence 1 and Sequence 3. 
The initial 2-week Run-in Period and the final 2-week Run-out Period will be study participant-
blind, with study participants not informed that they are receiving placebo, to limit the impact of 
any start-of-study or end-of-study induced placebo effects. The two 12-week Treatment Periods 
will be study participant-, investigator-, and sponsor-blind. It is important that study participants 
do not know when their treatment changes, whether it is going from Run-in to Period 1, Period 1 
to Period 2, or Period 2 to Run-out. 
The Baseline for each variable will be taken as the value measured prior to, but closest to, the 
treatment on Day 1. This may be measured on Day 1 prior to treatment or during Weeks -1 or ‑2 
depending on the endpoint. 
After approximatively 30 study participants have been randomized and these study participants 
have completed their 2 double-blind Treatment Periods, an interim analysis may be conducted 
with the possibility of stopping for efficacy or futility or continuing recruiting the remaining 
study participants. 
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The daily average pain over the previous 24 hours will be captured using the Pain NRS through a 
diary over a 10-day period within the Screening Period. Study participants require a minimum of 
7 out of the 10 daily Pain NRS assessments over this 10-day period to be eligible for 
randomization. All recorded Pain NRS scores over the 10-day period within the Screening Period 
will be used to calculate the Mean daily average 24 hours pain intensity ≥6 and <10 for Inclusion 
(for example, if 10 daily scores are available take the mean of the 10 days; if 9 daily scores are 
available take the mean of the 9 days and so on).  
During the Run-in Period and at the end of the Treatment Periods, the Pain NRS will be collected 
daily for 7 consecutive days following the assessment visit as described in the Schedule of 
Activities. For all other visits, the average pain for the preceding 24 hours prior to the visit will 
be captured by the Pain NRS for that day only. The timings of these assessments are described in 
the Schedule of Activities (Section 1.3). 
4.2 
Scientific rationale for study design 
The choice of the study population (study participants with severe FMS) is based on recent 
research findings (Goebel et al, 2021) suggesting that in patients with severe FMS 1) pathogenic 
IgG contribute to their clinical symptoms and 2) reduction of IgG is a potential therapeutic 
treatment approach. Nonclinical and clinical data generated on rozanolixizumab support the sc 
administration of rozanolixizumab in study participants with IgG autoantibody-mediated 
conditions. Patients with severe FMS have an unmet need due to the limited efficacious 
treatment options available. There is a burden of disease in patients with high levels of pain that 
impact overall function. 
The semi-crossover, three treatment-sequence design was chosen to allow for comparisons of the 
same study participant across different treatment periods in addition to comparisons between 
study participants, which leads to a substantially smaller sample size than a parallel-group 
design. An overview of estimates of variability and treatment effects from previous fibromyalgia 
and pain studies indicated that the variability between study participants is greater than that 
between the same study participant over time, which implies that a cross-over design is more 
efficient than a parallel-group design. However, a classic cross-over design is not appropriate, 
because if rozanolixizumab was followed by placebo any washout period is not feasible, as it 
would take too long for the IgG levels to return close to their Baseline levels. The third placebo-
only sequence was included to ensure a placebo control in the second period. 
The study includes single-blind, placebo-only Run-in and Run-out Periods before the start of 
Treatment Period 1 and after Treatment Period 2. The Run-in Period is included to allow any 
initial start-of-study placebo effect to stabilize, while the Run-out Period is included to limit the 
impact of shifts in endpoints that may be associated with the participants knowing that they have 
reached the end of study. 
4.3 
Justification for dose 
A rozanolixizumab dose of 560mg given weekly via sc infusion for at least 12 weeks is proposed 
in this study. Such a duration of dosing will ensure that sustained reduced IgG levels within the 
target range of ~70% to 80% reduction from Baseline will be maintained for a 6-week period 
once the PD steady state is achieved (after 6 weeks). Different treatment durations are being 
explored in this study (12 or 24 weeks on active treatment). 
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The planned dose of rozanolixizumab for this study is 560mg QW by sc infusion. As outlined 
below, this dose is justified by: 
• Clinical data from two Phase 2 studies showing a meaningful improvement at repeated doses 
of 7mg/kg in gMG and 10mg/kg in ITP. 
• Pharmacodynamic data showing a desired reduction in IgG levels of 70% from Baseline after 
repeated doses of 7mg/kg and 10mg/kg. 
• Simulations from a population PK-PD analysis showing comparable exposure and IgG 
response for the 560mg fixed dose and weight-tiered doses approximating 7mg/kg and 
10mg/kg doses. 
Rozanolixizumab has been studied in two Phase 2 studies in gMG and ITP with body weight 
normalized dosing (mg/kg). Repeated doses up to 10mg/kg and single doses up to 20mg/kg were 
generally well tolerated with an acceptable safety profile in these Phase 2 studies. In participants 
with gMG, clinically relevant improvements in day-to-day functioning were observed following 
treatment with rozanolixizumab 7mg/kg compared with placebo. In participants with ITP, 
rozanolixizumab produced clinically meaningful responses across the treatment groups 
(rozanolixizumab 4mg/kg to 20mg/kg at varying administration frequency), in all of the response 
variables defined by platelet counts. 
Phase 3 studies are being conducted to evaluate the efficacy and safety of rozanolixizumab in 
participants with gMG and ITP. The dose regimens being evaluated in the gMG studies are 
weight-tiered doses approximating 7mg/kg and 10mg/kg QW. For ITP, a weight-tiered loading 
dose approximating 15mg/kg followed by an initial weight-tiered maintenance dose 
approximating 10mg/kg Q2W or the exclusion of a loading dose is being evaluated; an initial 
weight-tiered maintenance dose approximating 10mg/kg every 1 week is also being evaluated. 
The proposed 560mg fixed dose of rozanolixizumab is selected to achieve a comparable range of 
exposures and IgG reductions as the weight-tiered doses that are being evaluated in the ongoing 
Phase 3 pivotal study in gMG. 
A population PK-PD model was developed based on observed PK and IgG data from the two 
Phase 2 studies (TP0001, MG0002) and two Phase 1 studies (UP0018 and UP0060). 
Rozanolixizumab exposure and IgG response to rozanolixizumab were comparable between 
healthy participants and the gMG and ITP populations. In addition, ethnicity was not found to 
affect PK or IgG response. Therefore, there are no anticipated changes in exposure or IgG 
responses, where the Baseline IgG levels are similar, between different indicated populations or 
ethnicities. 
Simulations performed using the population PK-PD model show that the planned dose of 560mg 
QW should: 
• Produce PK variability similar to that with weight-tiered dosing. 
• Achieve rozanolixizumab exposures that are consistent with those obtained with 
weight-tiered doses of 7mg/kg and 10mg/kg QW as used in the currently ongoing Phase 3 
studies. 
• Achieve and maintain a desired IgG reduction of 70% from Baseline, irrespective of body 
weight. 
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A fixed-dose regimen will simplify the dosing regimen to be more convenient for investigators 
and participants and to reduce the potential for dosing errors. Thus, a dose regimen of 560mg 
QW is planned for investigation in this study. 
4.3.1 
Rationale of targeted 70% IgG reduction 
Rozanolixizumab administration resulted in a rapid clearance of serum IgG levels in both healthy 
volunteers (UP0018 and UP0060) and participants with gMG (MG0002) or ITP (TP0001). 
Serum IgG levels decreased on average by 69% from Baseline levels after 2x3 weekly 
administrations of 7mg/kg in participants with gMG. The reduction in IgG was mirrored by a 
reduction in anti-acetylcholine receptor (AChR) autoantibodies in participants with gMG and 
was also associated with clinically meaningful improvements in clinical outcome scales 
(myasthenia gravis-activities of daily living [MG-ADL]) compared with placebo. 
A rozanolixizumab-induced IgG lowering of about 70% from Baseline is similar to that achieved 
with other FcRn antagonists and alternative strategies such as PLEX, and falls within the range 
associated with clinical benefit in various autoimmune indications. 
• A single PLEX reduces plasma IgG by about 30%; a minimum of 3 but commonly 5 to 
6 cycles are required to decrease specific IgGs by about 70% to 80%, which is the maximum 
reduction seen due primarily to the fact that IgG is constantly being synthesized at a high rate 
(Williams and Balogun, 2014; Kaplan, 2013). 
• Data in participants with CIDP treated with PLEX for 3 weeks showed decreases in IgG of 
60% to 75%. These decreases were associated with improvement in neurologic-disability 
scores, in scores on the weakness and reflex subsets of the neurologic-disability score, and in 
nerve conduction (Dyck et al, 1986). 
• Five to 6 PLEX cycles for a 70% to 80% reduction in total IgG is consistent with studies that 
have investigated the effect of PLEX on IgG autoantibody levels. An average of 5 to 6 cycles 
of PLEX are needed to get a clinical benefit, and this is typically associated with an 
approximately 70% reduction in the level of anti-AChR autoantibodies in gMG (Guptill et al, 
2016), antithyroid peroxidase autoantibodies in Hashimoto’s encephalopathy (Cook et al, 
2015), or autoantibodies in PV (Turner et al, 2000). 
• Phase 3 data for the FcRn antagonist efgartigimod showed that a reduction of total IgGs and 
anti-AChR autoantibodies was correlated to clinically meaningful improvements in MG 
disease scores (Vyvgart Prescribing Information, 2021). 
For FMS, indication-specific targets for IgG lowering are not yet established. The current 
assumption is that the desired level of IgG reduction would be similar to gMG and CIDP 
(~70%). 
4.4 
End of study definition 
A study participant is considered to have completed the study if he/she has completed all phases 
of the study, including the SFU Period. Study participants will have an EOT/EW Visit performed 
2 weeks after the Run-out Period or upon discontinuation of the study, followed by an SFU/EOS 
5 weeks after the Run-out Period. 
The end of study is defined as the date of the last visit of the last study participant in the study. 
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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 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Study participant must be ≥18 years and ≤70 years of age at the time of signing the informed 
consent form (ICF). 
Type of participant and disease characteristics 
2a. Study participant alone or with assistance of the caregiver is considered reliable and capable 
of adhering to the protocol visit schedule or medication intake according to the judgment of 
the investigator. 
3b. Study participant with a diagnosis of fibromyalgia as defined by the 2016 Revisions to the 
2010/2011 fibromyalgia diagnostic criteria (American College of Rheumatology Preliminary 
Diagnostic Criteria) plus the following characteristics during the Screening Period: 
At the Screening Visit, confirm: 
a. BPI-SF interference score ≥6 
b. Criterion removed  
c. Criterion removed  
d. Criterion removed 
e. Study participant has been diagnosed with FMS for at least 6 months 
f. Study participant has been having FMS symptomatology for at least 2 years before 
enrollment. 
Prior to randomization, confirm: 
a. Mean daily average 24 hours pain intensity ≥6 and <10 assessed by Pain NRS. This will 
be assessed over a 10-day period within the Screening Period. Study participants require 
a minimum of 7 out of 10 assessments over this 10-day period within the Screening 
Period. 
b. Pain NRS scores should be ≥4 at all completed assessments within this 10-day period.  
Rescreening can be allowed as described in Section 5.4. 
Weight 
4. Body weight of at least 35 kg.  
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Sex 
5b. Males or females 
Note: A female study participant is eligible to participate if she is not pregnant (see 
Appendix 4), not breastfeeding, and at least one of the following conditions applies: 
− Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 
OR 
− A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the 
Treatment Period and for at least 90 days after the final dose of IMP. 
Informed consent 
6. Capable of giving signed informed consent as described in Appendix 1 which includes 
compliance with the requirements and restrictions listed in the ICF and in this study protocol. 
Other 
7. Criterion removed. 
8. Criterion removed. 
5.2 
Exclusion criteria 
Study participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
1. Study participant has been diagnosed with FMS for >15 years. 
2. Study participant has any systemic autoimmune inflammatory disease (eg, rheumatoid 
arthritis, systemic lupus erythematosus, and inflammatory arthritis [including ankylosing 
spondylitis, psoriatic arthritis]). 
3. Study participant has any medical or psychiatric or separate chronic pain condition (pain 
from traumatic injury or structural disease, regional pain syndromes, multiple surgeries or 
failed back syndrome, or any other chronic pain not related to FMS) that, in the opinion of 
the investigator, could jeopardize or would compromise the study participant’s ability to 
participate in this study or the ability to assess FMS-related pain. 
4. Study participant has a current history of alcohol or drug use disorder, as defined in 
Diagnostic and Statistical Manual of Mental Disorders V, within the previous 12 months 
prior to the Screening Visit. 
5. Study participant has a known hypersensitivity to any components of the study medication or 
any other anti-FcRn medications. This includes a known history of hyperprolinemia, since 
L-proline is a constituent of the rozanolixizumab formulation. 
6. Study participant has active neoplastic disease or a history of neoplastic disease within 
5 years of study entry (except for basal or squamous cell carcinoma of the skin or carcinoma 
in situ of the uterine cervix which has been definitely treated with SoC approaches). 
7. Criterion removed 
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8a. Study participant has severe renal impairment, defined as estimated glomerular filtration rate 
<30mL/min/1.73m2 (calculated using Modification of Diet in Renal Disease [MDRD] study 
equation), at Screening visit. 
9a. Study participant has a clinically important active infection (including unresolved or not 
adequately treated infection) as assessed by the investigator. 
10. Study participant has chronic inflammatory demyelinating polyneuropathy. 
11. Study participant has current unstable liver or biliary disease, per investigator assessment, 
defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, 
esophageal or gastric varices, persistent jaundice, or cirrhosis. Note an exception is stable 
chronic hepatobiliary conditions (including Gilbert’s syndrome, asymptomatic gallstones). 
12. Study participant has a current or medical history of primary immunodeficiency. 
13. Criterion removed. 
14a. 
Study participants meet any of the following TB exclusion criteria: 
• Known active TB disease 
• History of active TB involving any organ system unless adequately treated according to 
World Health Organization/US Center for Disease Control therapeutic guidance and 
proven to be fully recovered upon consult with a TB specialist 
• Latent tuberculosis infection (LTBI) (unless appropriate prophylaxis is initiated at least 
1 week prior to IMP dosing and will be continued to completion of prophylaxis). 
Prophylaxis should be in accordance with applicable clinical guidelines and TB specialist 
judgment based on the origin of infection 
• High risk of exposure to TB infection, as assessed by the investigator 
• Criterion removed 
For further information relating to definitions of known active TB, past history of TB, LTBI, 
and high risk of acquiring TB infection, see Appendix 12 (Section 10.12). 
15. Criterion removed 
16. Study participant has a history of solid organ transplant or hematopoietic stem cell/marrow 
transplant. 
17. Study participant has a history of chronic ongoing infections (eg, Hepatitis B or C, human 
immune deficiency virus [HIV], or who tests positive for HIV, Hepatitis B or C at Screening 
Visit. 
• Presence of Hepatitis B surface antigen at the Screening Visit. 
• Positive Hepatitis C antibody test result at Screening or within 3 months prior to the IMP 
dose. NOTE: Study participant with a positive Hepatitis C antibody due to prior resolved 
disease can be enrolled only if a confirmatory negative Hepatitis C RNA test is obtained. 
18. Study participant has undergone a splenectomy. 
19. Study participant is pregnant or lactating. 
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20 Criterion removed. 
21a. 
Study participant  
• Has suicide attempt in the past 2 years (including an active attempt, interrupted attempt, 
or aborted attempt),  
• OR had suicidal ideation with at least some intent to act in the past 6 months as indicated 
by a positive response (Yes) to either Question 4 or Question 5 of the Columbia Suicide 
Severity Rating Scale (C-SSRS) at Screening or Baseline (Visit 3);  
• OR is otherwise judged clinically to be at a serious suicidal risk based on the 
investigator’s judgment.  
Prior/Concomitant therapy 
22. Study participant has been treated with prohibited immunosuppressive medications, 
biologics, or other therapies within the exclusion period (see Section 6.5.2). 
23. Study participant has current treatment with prednisolone or equivalent (except for a short 
course to treat, for example, an episode of asthma or chronic obstructive pulmonary disease 
exacerbation). 
24. Study participant has current treatment with morphine or equivalent of >80mg/day 
(>40mg/day if morphine or equivalent are taken in association with gabapentin 
[>1200mg/day] or pregabalin [>150mg/day]). 
25a. Study participant has received a live vaccination within 4 weeks prior to Visit 1 or intends 
to have a live vaccination during the study or within 8 weeks following the final dose of 
IMP (Visit 28).  
Prior/Concurrent clinical study experience 
26. Study participant has previously been randomized in this study (rescreening for screen-failed 
participants is allowed with prior consultation and permission of the medical monitor/study 
physician; see Section 5.4). 
27. Study participant has participated in another study of an IMP (and/or an investigational 
device) within the previous 30 days or 5 half-lives prior to screening (whichever is longer) or 
is currently participating in another study of an IMP (and/or an investigational device). 
Diagnostic assessments 
28. Study participant has alanine transaminase (ALT), aspartate aminotransferase (AST), or 
alkaline phosphatase (ALP) that is >2x upper limit of normal (ULN). 
• If study participant has >ULN for ALT, AST, or ALP that does not meet the exclusion 
limit at Screening, the tests must be repeated prior to dosing to ensure there was no 
further ongoing clinically relevant increase. In case of a clinically relevant increase as per 
the investigator's judgment, the study participant must be excluded. 
• Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit (>2xULN) 
may be repeated once for confirmation. This includes rescreening. If any of the repeated 
tests (ALT, AST, or ALP) are >2xULN, the study participant will meet the exclusion 
criterion #28 and the study participant must be excluded. 
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• For randomized study participants with a Baseline result >ULN for ALT, AST, ALP, or 
total bilirubin but <1.5xULN, a Baseline diagnosis and/or the cause of any clinically 
meaningful elevation will have to be understood and recorded in the electronic case 
report form (eCRF). 
29. Study participant has bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if 
bilirubin is fractionated and direct bilirubin <35%). 
30a. Study participant has IgG ≤5.5g/L at the Screening Visit. 
31. Study participant has an absolute neutrophil count <1500 cells/mm3 at the Screening Visit. 
32. Study participant has a planned major elective surgical procedure during their participation in 
the study. 
33. Criterion removed 
5.3 
Lifestyle restrictions 
There are no lifestyle restrictions during this study. 
5.3.1 
Meals and dietary restrictions 
There are no meal or dietary restrictions during this study. 
5.3.2 
Caffeine, alcohol, and tobacco 
There are no restrictions on caffeine or tobacco during this study. Study participants are to avoid 
excessive alcohol consumption during the study. 
5.3.3 
Activity 
There are no restrictions on activity during this study. 
5.4 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomized to study treatment. 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 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). 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened, following discussion with the sponsor’s medical monitor or study physician. 
Rescreened study participants should be assigned a new study participant number for rescreening 
and repeat all Screening assessments.  
If a study participant has 1 isolated test result outside the specific range which is deemed 
clinically nonsignificant, the abnormal value may be rechecked at the discretion of the 
investigator, following discussion with the sponsor’s medical monitor or study physician. If the 
normalization of the test result occurs within the Screening Period, then no other Screening 
procedures need to be repeated. 
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes rescreening. 
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6 
STUDY TREATMENTS 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
6.1 
Treatments administered 
Study participants will be randomized to one of three different treatment sequences at the 
beginning of the 2-week Run-in Period. 
All study participants will receive placebo during the Run-in Period. Study participants will 
receive either rozanolixizumab (Sequence 1) or placebo QW (Sequence 2 and 3) for the first 
12 weeks. At the end of 12 weeks, study participants who were on active (Sequence 1) will 
receive an additional 12 weeks of rozanolixizumab. 
In the first cohort receiving placebo (Sequence 2), study participants will receive 12 weeks of 
rozanolixizumab, and in the second placebo cohort (Sequence 3), study participants will receive 
an additional 12 weeks of placebo. 
At the end of the second Treatment Period, all study participants will receive placebo during a 
2-week Run-out Period. 
Study treatment will be administered as an sc infusion over approximately 12 minutes. The 
infusion duration may be increased at the discretion of the investigator.  
ARM Name 
Sequence 1 
Sequence 2 
Sequence 3 
Intervention 
name 
Placebo (Run-in and Run-
out) 
Rozanolixizumab 
(Treatment Period 1+2) 
Placebo (Run-in, 12-week 
Treatment Period 1 + 
Run-out) 
Rozanolixizumab 
(Treatment Period 2) 
Placebo (Run-in, 
24 weeks [Treatment 
Period 1+2], Run-out) 
Type 
Placebo + Biologic 
Placebo + Biologic 
Placebo 
Dose 
formulation 
Solution for injection 
Solution for injection 
Solution for injection 
Unit dose 
strength for the 
Treatment 
Period 
A glass vial containing 
rozanolixizumab at a 
concentration 
of 140mg/mL, formulated 
with 30mM L-histidine, 
250 nM L-proline, 0.03% 
(w/v) polysorbate 80 and 
pH 5.6 
Dose of 560mg 
0.9 % w/v saline 
(Placebo) 
Or  
A glass vial containing 
rozanolixizumab at a 
concentration of 
140mg/mL, formulated 
with 30mM L-histidine, 
250 nM L-proline, 0.03% 
(w/v) polysorbate 80 and 
pH 5.6 
Dose of 560mg 
0.9 % w/v saline 
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Dosage levels 
Placebo weekly for 
2 weeks (Run-in), then 
rozanolixizumab 560mg 
weekly for 24 weeks 
(Treatment Period 1 + 2), 
followed by Placebo 
weekly for 2 weeks (Run-
out) 
Placebo weekly for 
2 weeks (Run-in), then 
Placebo weekly for 
12 weeks (Treatment 
Period 1), followed by 
rozanolixizumab 560mg 
weekly for 12 weeks 
(Treatment Period 2), 
followed by Placebo 
weekly for 2 weeks (Run-
out) 
Placebo weekly for 
2 weeks (Run-in), then 
Placebo weekly for 
24 weeks (Treatment 
Period 1 + 2), followed 
by Placebo weekly for 
2 weeks (Run-out) 
Route of 
administration 
Subcutaneous infusion 
Subcutaneous infusion 
Subcutaneous infusion 
Use 
Experimental 
Placebo comparator and 
Experimental (active) 
Placebo comparator 
IMP and NIMP 
IMP 
IMP 
IMP 
Sourcing 
Provided centrally by the 
sponsor 
Provided centrally by the 
sponsor 
Provided centrally by the 
sponsor 
Packaging and 
labeling 
Packaging will be 
described in the IMP 
Handling Manual. 
Packaging will be labelled 
as required per country 
requirement. 
Packaging will be 
described in the IMP 
Handling Manual. 
Packaging will be labelled 
as required per country 
requirement. 
Packaging will be 
described in the IMP 
Handling Manual. 
Packaging will be 
labelled as required per 
country requirement. 
Current/Former 
name or alias 
UCB7665 
UCB7665 + not 
applicable for placebo 
Not applicable 
IMP=investigational medicinal product; NIMP=non-investigational medicinal product; w/v=weight/volume 
6.2 
Preparation, handling, storage, and accountability requirements 
The investigator or designee must confirm that appropriate temperature conditions have been 
maintained during transit for all study treatment received, and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment and only authorized site staff 
may supply or administer study treatment. All study treatments must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions, with access limited to the investigator and authorized site staff. 
Details on the preparation of study treatment for infusion, rate of infusion, administration, 
appropriate records handling, and blinded and unblinded site personnel roles are provided in the 
IMP Handling Manual. All site personnel and healthcare professionals delegated to handle study 
treatment storage, preparation, and administration must be trained to IMP Handling Manual. 
The investigator or delegate is responsible for study treatment accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records). 
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In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual. 
Further guidance and information for the final disposition of unused study treatment are provided 
in the IMP Handling Manual. 
6.2.1 
Drug accountability 
A Drug Accountability form will be used to record study medication dispensing and return 
information on a by-study 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 may assign some of the investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of study medication until returned or destroyed. 
The investigator must ensure that the study medication is used only in accordance with the 
protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers/partially used), unused, damaged, and/or expired study medication must be reconciled 
and either destroyed at the site according to local laws, regulations, and UCB Standard Operating 
Procedures or returned to UCB (or designee). Investigational medicinal product intended for the 
study cannot be used for any other purpose than that described in this protocol. 
6.3 
Measures to minimize bias: randomization and blinding 
Study participants will be randomized to the appropriate treatment (active or placebo) in their 
cohort using the Trial Supply Management system. The unblinded randomization list will be 
provided to pharmacies via a digital format. After informed consent is obtained, participants will 
be allocated a unique Screening number. 
An interactive response technology (IRT) will be used for assigning eligible study participants to 
a treatment regimen (as applicable) based on a predetermined production randomization and/or 
packaging schedule provided by UCB (or designee). The IRT will generate individual 
assignments for kits of study medication, as appropriate, according to the visit schedule. 
To enroll a study participant (Visit 0), the investigator or designee will contact the IRT and 
provide brief details about the study participant to be enrolled. Each study participant will 
receive a 5-digit number assigned at Screening that serves as the study participant identifier 
throughout the study. The study participant number will be required in all communication 
between the investigator or designee and the IRT regarding a particular study participant. Study 
participant numbers and kit numbers will be tracked via the IRT. 
To randomize a study participant, the investigator or designee will contact the IRT and provide 
brief details about the study participant to be randomized. The IRT will automatically inform the 
investigator or designee of the study participant’s randomization number. The IRT will allocate 
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kit numbers to the study participant based on the study participant number during the course of 
the study. The randomization number must be incorporated into 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 will be allocated and maintained by IRT system. 
The following individuals will receive the randomization code at the start of the study: 
• Sponsor Patient Safety staff for reporting SAEs to regulatory authorities 
• Designated bioanalytical staff analyzing PK samples 
• IRT provider 
 
 
 
 The unblinded pharmacy monitors from the Contract Research Organization (CRO) and the 
Clinical Supply Set-Up Manager/Clinical Supply Planner, and the unblinded Clinical Project 
Manager (CPM)(or designee) will also have access to the treatment allocations and to the drug 
accountability records, if applicable. Further details are provided in the IMP Handling Manual 
and Site Unblinded Team Management Plan. 
Due to differences in presentation between rozanolixizumab and placebo, special precautions 
will be taken to ensure blinding. Both products have packaging differences (unblinded labels) but 
also physical appearance differences (packaging presentation, volumes, color, viscosity). The 
IMP preparation will be performed by unblinded personnel. Please note that the difference in 
appearance of the two IMPs can be seen in the syringe but not in the tubing. Therefore, only the 
syringe will be covered by blinding stickers (see IMP Handling Manual). 
The IMP administration will be performed by blinded qualified site staff. 
The following individuals may, as necessary, request access to the randomization code from IRT 
as indicated: 
• Interim analysis biostatistician/statistical programmer 
• Members of the SMC who participate in unblinded sessions will be given information about 
the IMP allocation for those study participants for whom data are provided at these sessions 
(see also Section 9.7.2). 
• The designated unblinded statistician and supporting programmer(s) responsible for the 
preparation of the data outputs for the SMC review and/or any interim analyses. 
Certain clinical laboratory results have the potential to unblind the investigator, site personnel, 
and study team. These results will not be reported to investigative sites or other blinded 
personnel (see Section 10.2 for a list of these clinical laboratory parameters). A medical monitor 
independent from the study team and unblinded to the serum IgG and albumin levels, but blinded 
to actual treatment assignment (an independent unblinded medical monitor) will monitor these 
parameters during the Treatment Period. If temporary treatment discontinuation due to low 
serum IgG levels or low serum albumin levels (as per Section 7.1.4) is required, the independent 
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unblinded medical monitor will contact the IRT system to initiate mock infusions with only 
placebo. This procedure will take place irrespective of the randomized IMP. Allocation of mock 
kit numbers will be handled via the IRT. The independent unblinded medical monitor will re-
initiate the IMP via the IRT system when the serum IgG and/or albumin levels have returned to 
protocol-defined thresholds specified in Section 7.1.4. 
Further details of maintenance of the study treatment blind are provided in the IMP Handling 
Manual and Site Unblinded Team Management Plan. 
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 the study 
participant has been allocated by contacting the IRT. All sites will be provided with details of 
how to contact the system for code breaking at the start of the study. The medical monitor or 
equivalent should be consulted prior to unblinding, whenever possible. 
The CPM and medical monitor will be informed immediately via the IRT when a code is broken, 
but will remain blinded to specific treatment information. Any unblinding of the study 
medication performed by the investigator must be recorded in the source documents and on the 
Study Termination eCRF page. 
Inadvertent unblinding must be listed as a major protocol deviation. 
6.4 
Treatment compliance 
Drug accountability must be recorded on the Drug Accountability form (Section 6.2.1). 
6.5 
Concomitant medications/treatments 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
The following concomitant treatments are permitted during the study: 
• Medications or therapies for FMS or chronic pain 
− PRN (as needed) analgesics taken as over the counter (OTC) (eg, ibuprofen, paracetamol, 
codeine) and/or prescribed (eg, opioids) if initiated 
 before randomization.   
− Prescribed regular opioids (short or long acting) up to a total opioid equivalent dose of 
80mg/day of morphine (including PRN opioids, if taken). For regular opioids, the patient 
must have been on the stable equivalent daily dose of morphine for 
 after 
initiation/up-titration or
 after down-titration.  
− Regular antidepressants or gabapentinoids (eg, pregabalin, gabapentin) prescribed for 
pain and/or sleep if started 
 and stable for 
 before 
randomization.  
− Migraine treatment-related drugs that are not antibody-based.  
− Any other pain therapies are only permitted if deemed acceptable in the judgment of the 
investigator and, where appropriate, in discussion with the medical monitor. 
− Any pain management programs are only permitted if deemed acceptable in the judgment 
of the investigator and in discussion with the medical monitor. 
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6.5.2 
Prohibited concomitant treatments (medications and therapies) 
Prohibited medications and therapies relative to Baseline are summarized in the table below. The 
use of these medications is also prohibited during the study and the use of these may result in the 
study participant being discontinued from IMP. Investigators should contact the medical monitor 
where possible to discuss the discontinuation of IMP in advance. 
Concomitant medications prohibited during the study are presented in Table 6-1. 
Table 6-1: 
Concomitant medications prohibited during the study 
Generic Name (commercial/trade name) 
Exclusionary period relative to Visit 1 
(regardless of route) 
Immunosuppressive medications 
Cyclophosphamide (Cytoxan®) 
6 months 
Cyclosporine (Neoral®) 
4 weeks 
Biologics 
Monoclonal therapeutic antibodies 
Used within 6 months of Visit 1 
or used ≥6 months prior to Visit 1 with B-cells 
that have not returned to normal levels 
Others 
 
Antineoplastics or treatments for neoplastic 
disease (including anti-PD1 monoclonal 
antibodies) 
3 months 
Dabigatran 
2 weeks 
Intravenous methylprednisolone 
4 weeks 
Prednisone (or other steroids equivalent)a 
4 weeks 
Intravenous or subcutaneous immunoglobulin 
6 weeks 
Plasma exchange or plasmapheresis 
6 weeks 
Immunoadsorption 
6 weeks 
PD1 = programmed cell death protein 1 
a  Except for a short course to treat, for example, an episode of asthma or chronic obstructive pulmonary disease 
exacerbation. 
 
Table 6-2: 
Prohibited concomitant medications and therapies relative to the last 
rozanolixizumab dose 
Generic Name (commercial/trade name) 
Exclusionary period relative to Visit 1 
(regardless of route) 
Live vaccination 
4 weeks 
Treatment with IgG based monoclonal antibodies 
8 weeks 
 
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6.5.3 
Rescue medication 
The use of OTC analgesics (eg, ibuprofen, paracetamol, codeine) and other medications for 
treatment of FMS is allowable at a stable dose during the study (see Section 6.5.1). The use of 
these medications is considered rescue medication if the dose is increased relative to the stable 
dose or if an additional medication not used at Screening is considered necessary by the 
investigator. The date and time of rescue medication administration as well as the name and 
dosage regimen of the rescue medication must be recorded in the eCRF under concomitant 
medication (see Schedule of Activities, Section 1.3). As the rescue medication might overlap 
with the permitted medication, the rescue medication can be identified as a new analgesic not 
listed at screening or as a change in the usual dosage regimen of a permitted SoC analgesic 
medication. 
6.6 
Dose modification 
Dose modification of IMP is not permitted in this study. However, temporary discontinuation of 
IMP may occur as detailed in Section 7.1.4. 
6.7 
Criteria for study hold or dosing stoppage 
After approximatively 30 study participants have completed their 2 treatment periods, a planned 
interim analysis may be conducted (Section 9.7.1). A decision to halt the study may be taken 
based on this analysis, if performed. 
The sponsor’s decision for study hold may also be based on an SMC recommendation (see 
Section 9.7.2). 
6.8 
Treatment after the end of the study 
There are no plans for the provision of rozanolixizumab after the end of the study. The study 
participant should discuss any alternative treatment options (if needed after the study) with their 
healthcare provider. 
7 
DISCONTINUATION OF STUDY MEDICATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study medication 
In addition to algorithmic stopping criteria, management of AEs is ultimately at the 
investigator’s discretion. 
7.1.1 
Liver chemistry stopping criteria 
Discontinuation of study treatment for abnormal liver function should be considered by the 
investigator when a study participant meets one of the conditions outlined in Figure 7-1 or if the 
investigator believes that it is in best interest of the study participant. 
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Figure 7-1: Liver Chemistry Stopping Criteria and Increased Monitoring 
Algorithm 
 
AST=aspartate aminotransferase; ALT=alanine transaminase; INR=international normalized ratio; SAE=serious 
adverse event; ULN=upper limit of normal 
Specific assessments and follow-up actions for potential drug-induced liver injury (PDILI) are 
provided in Appendix 6 (Section 10.6). 
7.1.2 
Other permanent discontinuation criteria 
Study participants must permanently discontinue IMP if any of the following events occur: 
1. Study participant develops an illness that would interfere with their continued participation. 
2. Study participant has a significant infective episode including but not limited to 
bacteremia/sepsis, infectious meningitis, septic arthritis, osteomyelitis, complicated 
pneumonia, or visceral abscess which may or may not result in hospitalization. This list is not 
intended to be all inclusive, and the investigator is expected to apply their clinical judgment 
on continuing IMP based on the clinical situation (see Appendix 14; Section 10.14). 
3. Study participant has an AE of severe or serious hypersensitivity, infusion-related reaction 
(Appendix 15; Section 10.15), or anaphylaxis requiring corticosteroid and/or epinephrine 
therapy (Sampson et al, 2006). 
4. Study participant has a recurrence of aseptic meningitis (see also Appendix 13; 
Section 10.13). 
 
Continue Study Treatment 
Discontinue Study Treatment 
Plus
Bilirubin≥2x
ULN (>35% 
direct) 
or plus
INR>1.5, if 
measured*
Possible
Hy’s Law
ALT≥3xULN
ALT≥5xULN
ALT≥3xULN
Plus
Symptoms of 
liver injury
or 
hypersensitivity
ALT≥3xULN
but able to 
monitor 
weekly for 
4 weeks
No
Yes
Yes
Yes
Yes
No
No
No
No
Yes
ALT≥3xULN
persist for
4 weeks or 
stopping 
criteria 
met
Yes
No
Yes
➢If subject to be monitored weekly must refer to Liver Safety Required  Actions and  Follow  up 
Assessments  section  in  the  Appendix
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 patients on anticoagulants) 
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5. Participant meets PDILI permanent discontinuation criteria (see Appendix 6, Section 10.6).  
6. Study participant for whom further examinations result in a diagnosis of active TB, or if the 
study participant is diagnosed with LTBI with no initiation of TB preventive therapy, 
prematurely discontinues TB preventive therapy, or, in the opinion of the investigator or 
sponsor is noncompliant with TB preventive therapy. An EW visit must be scheduled as soon 
as possible, but not later than the next regular visit. 
7. Study participant has new onset or recurrent neoplastic disease (except for superficial basal 
or squamous cell carcinoma of the skin not requiring targeted biological therapy, 
chemotherapy, or radiation). 
8. Study participant has active suicidal ideation as indicated by a positive response (Yes) to 
either Question 4 or Question 5 of the “Since Last Visit” version of the C-SSRS. The study 
participant should be referred immediately to a mental healthcare professional and must be 
withdrawn from the study. 
7.1.3 
Level of follow up to be considered when permanent discontinuation 
from IMP occurs 
In circumstances where permanent discontinuation from IMP may occur (Section 7.1.1 and 
Section 7.1.2), the investigator is to discuss with the study participant the appropriate processes 
for discontinuation from IMP and must discuss with the study participant the options for 
continuation of the assessments in the Schedule of Activities (Section 1.3), including different 
options of follow up (eg, in person, by phone/mail, in correspondence/communication with other 
treating physicians, from the review of medical records) and collection of data, including 
endpoints and AEs. 
Study participants who have discontinued IMP should not be automatically removed from the 
study. Whenever safe and feasible, it is imperative that study participants remain on study to 
ensure safety surveillance and/or collection of outcome data. The investigator must document the 
level of follow up that is agreed to by the study participant, any changes to the scheduled visits 
and assessments, and the plan for follow up that is agreed to by the study participant. In regards 
to changes to scheduled visits, for the level of follow up, it is recommended the EOT/EW Visit 
and the SFU/EOS Visit be prioritized. 
If the study participant does not want to continue the IMP and withdraws consent (refer to 
Section 7.2), investigators should contact the medical monitor, whenever possible, to discuss the 
withdrawal of a study participant in advance. 
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7.1.4 
Temporary discontinuation 
Study participants must be temporarily discontinued from the IMP if any of the following 
events occur: 
1. The study participant develops an event of hypogammaglobulinemia with a serum total IgG 
reported below the lower limit of quantification (LLOQ) (currently 1.09g/L), irrespective of 
infection. Study participant may resume treatment when IgG level returns to ≥2g/L. In view 
of re-initiating the IMP, additional samples will be collected to monitor study participants’ 
IgG levels during the period of temporary discontinuation. In order to preserve the blind, 
additional study participants will be selected at random and requested to provide additional 
samples. 
2. Study participant develops an event of hypoalbuminemia with serum albumin level <2g/dL. 
When the serum albumin level returns to ≥2.5g/dL, the study participant may be allowed to 
resume treatment with IMP. Ad hoc assessments can be performed to monitor recovery of 
albumin levels. In view of re-initiating the IMP, additional samples will be collected to 
monitor study participants’ serum albumin levels during the period of temporary 
discontinuation. In order to preserve the blind, additional study participants may be selected 
at random and requested to provide additional samples. 
If IMP treatment is resumed, the next dose should be continued as previously scheduled. No 
“make up” dose is permitted. The study participant should subsequently follow the visit 
schedule as described in the protocol and the eCRF should be completed accordingly. 
3. Study participant has a suspected drug-induced aseptic meningitis. The IMP may be restarted 
if clinically appropriate when signs and symptoms have resolved. 
Study participants may be temporarily discontinued from the IMP if the following event occurs: 
1. Study participant develops a nonserious persisting or recurrent infection with serum total IgG 
level reported between the LLOQ (currently 1.09g/L) and <2g/L. Upon resolution of 
infection and return of IgG level to ≥2g/L, the study participant may be allowed to resume 
treatment. 
2. Removed 
If IMP treatment is resumed, continue the next dose as previously scheduled. No “make up” dose 
is permitted. The participant should subsequently follow the visit schedule as described in the 
protocol and the eCRF should be completed accordingly. 
7.2 
Participant discontinuation/withdrawal from the study 
Study participants are free to withdraw from the study at any time, without prejudice to their 
continued care. 
A study participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If the study participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
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If a study participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested. The investigator must document this in the site study records, suspend 
further sample shipments, and inform the site monitor immediately. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
7.2.1 
Study withdrawal criteria 
Study participants must be withdrawn from the study if any of the following events occur: 
1. Study participant withdraws his/her consent. 
2. There is confirmation of a pregnancy during the study, as evidenced by a positive serum 
pregnancy test. 
3. The sponsor or a regulatory agency requests withdrawal of the study participant. 
4. Removed 
5. Study participant has active suicidal ideation as indicated by a positive response (Yes) to 
either Question 4 or Question 5 of the “Since Last Visit” version of the C-SSRS. The study 
participant should be referred immediately to a mental healthcare professional and must be 
withdrawn from the study. 
If a study participant withdraws from the study, the following procedures should be completed: 
• The study participant should not receive further doses of IMP. 
• The study participant should return for an EW Visit scheduled as soon as possible, but no 
later than the next scheduled visit. 
• SFU or EOS Visit should be scheduled 6 weeks after the study participant has discontinued 
his/her IMP. 
Study participants may be withdrawn from the study, at the discretion of the investigator, 
medical monitor, and study physician, if any of the following events occur: 
1. Study participant is noncompliant with the study procedures or medications in the opinion of 
the investigator. 
2. Study participant takes prohibited concomitant medications as defined in this protocol 
(Section 6.5.2). 
3. Study participant develops an illness that would interfere with his/her continued 
participation. 
Investigators should contact the medical monitor, whenever possible, to discuss the withdrawal 
of a study participant in advance. 
For the study participants who are withdrawn from the study, the EOT Visit must be scheduled 
as soon as possible, but no later than the next regular visit. Study participants will be encouraged 
to complete the SFU Period. 
Participants who are randomized but withdraw prior to dosing at Day 1 may be replaced. 
Replacement study participants will be assigned the same treatment that was assigned to the 
withdrawn study participant. 
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7.3 
Lost to follow-up 
A study participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a study participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the study participant and reschedule the missed visit as soon 
as possible and counsel the study participant on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the study participant wishes to and/or should 
continue in the study. 
• Before a study participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the study participant (at least 1 phone call and 
1 written message to the study 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 study participant, must be recorded in the 
source documents. The eCRF must document the primary reason for withdrawal. 
Should the study participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up documented in the eCRF. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities (Section 1.3). 
Study visits should preferably be conducted at the same time of the day throughout the study. 
Some study-specific investigations may not be conducted according to the study protocol during 
a pandemic or other exceptional circumstance (eg, extreme weather) due to the need to 
implement safety measures and guidance from regulatory authorities. In such a situation, which 
may be accompanied by local or global containment or other measures, sites may need to 
prohibit access to study participants and study-related personnel. Study participants’ visits to the 
study site may be replaced by contingency measures. These measures are primarily established to 
ensure the safety of study participants during the course of the study and to maintain the study 
participants’ treatment schedules, if the investigator considers it appropriate. These measures 
include, but are not limited to, virtual visits or home-nursing visits replacing site visits, eg, 
telemedicine contacts or home-nursing visits when treatment and/or blood sampling is scheduled. 
The contingency measures are described in a contingency plan which will be maintained by UCB 
for the respective study. The contingency measures are shared with the investigator and the 
respective study-related personnel as soon as there are indications that it is necessary to 
implement any of the measures. 
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 study participant should continue or discontinue study treatment. 
Adherence to the study design requirements, including those specified in the Schedule of 
Activities (Section 1.3), is essential and required for study conduct. 
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All Screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. Screening assessments can be performed on different days throughout 
the Screening Period, if required. 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. 
The maximum amount of blood collected from each study 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. 
8.1 
Efficacy assessments 
Planned time points for all efficacy assessments are summarized in the Schedule of Activities 
(Section 1.3). 
8.1.1 
Brief Pain Inventory-Short Form 
The BPI-SF was designed to measure multiple clinically relevant aspects of pain such as pain 
intensity and interference from pain in cancer populations. There are two versions; the short 
version is the most commonly used and is often included in the context of clinical trials 
(Williams and Arnold, 2011). The short form of the BPI is a self-administered questionnaire used 
to evaluate the severity of a study participant’s pain and the impact of this pain on the study 
participant's daily functioning. The BPI-SF assesses for the location of pain, pain intensity, and 
functional interference from pain. The BPI-SF should be completed by the study participants in a 
quiet place prior to other PROs or protocol-specified assessments at each visit including dosing 
on dosing days. 
The 4 BPI-SF severity items include: worst pain in last 24 hours, least pain in last 24 hours, pain 
on average, and pain right now. Each item is rated on a 0 (no pain) to 10 (pain as bad as you can 
imagine) scale with a recall period of 24 hours. 
The 7 BPI-SF interference items include: general activity, mood, walking ability, normal work 
(including housework), relations with other people, sleep, and enjoyment of life. Each item is 
rated on a 0 (does not interfere) to 10 (completely interferes) scale with a recall period of 
24 hours. The arithmetic mean of the 7 interference items can be used as a measure of pain 
interference. 
8.1.2 
Pain NRS 
The Pain NRS is a numeric version of the VAS in which a respondent selects a whole number 
that best describes “How much pain have you experienced on average over the past 24 hours?” 
The 11-point Pain NRS ranges from 0 (no pain) to 10 (pain as bad as you can imagine). 
The daily average pain over the previous 24 hours will be captured using the Pain NRS through a 
diary over a 10-day period within the Screening Period. Study participants require a minimum of 
7 out of the 10 daily Pain NRS assessments over this 10-day period to be eligible for 
randomization. All recorded Pain NRS scores over the 10-day period within the Screening Period 
will be used to calculate the Mean daily average 24 hours pain intensity ≥6 and <10 for Inclusion 
(for example, if 10 daily scores are available take the mean of the 10 days; if 9 daily scores are 
available take the mean of the 9 days and so on).  
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During the Run-in Period and at the end of the Treatment Periods, the Pain NRS will be collected 
daily for 7 consecutive days following the assessment visit as described in the Schedule of 
Activities. For all other visits, the average pain for the preceding 24 hours prior to the visit will 
be captured by the Pain NRS for that day only. 
8.1.3 
Pressure pain threshold 
Pressure pain threshold will be assessed by pressure algesiometry before dosing. Pressure 
algesiometry will be performed at 2 sites on the body: (1) the lateral forearm and (2) the 
contralateral anterior thigh. 
8.1.4 
Revised Fibromyalgia Impact Questionnaire 
The FIQR is a 21-item questionnaire with a recall period of 7 days. The FIQR includes 
3 domains: function, overall impact, and symptoms. Each item is based on an 11-point numeric 
rating scale. The FIQR will be completed by the participant during study visits. 
8.1.5 
Fatigue NRS 
The Fatigue NRS is a numeric version of the VAS in which a respondent selects a whole number 
that best describes “How much fatigue have you experienced on average over the past 
24 hours?” The 11-point Fatigue NRS ranges from 0 (no fatigue) to 10 (fatigue as bad as you can 
imagine). The Fatigue NRS will be completed by the participant at home/during study visits. 
8.2 
Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). 
8.2.1 
Physical examination 
For full and brief physical examinations, investigators should pay special attention to clinical 
signs related to previous serious illnesses, as well as signs and symptoms of infections. 
Clinically relevant findings or worsening of previous findings will be recorded as AEs. 
A full physical examination will include, at a minimum, general appearance; ear, nose, and 
throat; eyes, hair, and skin; and assessments of the cardiovascular, respiratory, gastrointestinal 
(GI), and musculoskeletal systems. Weight and height will also be measured and recorded at 
Visit 0 and the SFU/EOS Visit with the study participant wearing light clothing and without 
wearing shoes. 
A brief physical examination will include, at a minimum, assessments of the skin, respiratory 
system, cardiovascular system, and abdomen (liver and spleen). 
8.2.2 
Neurological examination 
In addition to the Screening and EOT/EW Visits, a full neurological examination should be 
performed for any study participant who experiences severe and/or serious headache or 
suspected aseptic meningitis (see Section 10.13). 
A full neurological examination will include: (1) General appearance, including motor activity 
and meningeal signs and, if indicated, the following assessments will be performed; (2) Cranial 
nerves examination; (3) Motor system examination, including muscle tone and power and 
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sensory system examination – light touch; (4) Reflexes, including deep tendon reflexes; 
(5) Coordination, gait (if possible); and (6) Fundoscopy. 
A brief neurological examination will include a selected assessment of the following categories, 
including but not limited to: general (including level of consciousness, mental status, and 
meningeal signs), reflexes, muscle power, and coordination. 
8.2.3 
Vital signs 
Oral, tympanic, and axillary temperature, pulse rate, and blood pressure will be assessed. 
Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the 
study participant in a quiet setting without distractions (eg, television, cell phones). All 
measurements will be assessed in a sitting position with a completely automated device. Manual 
techniques will be used only if an automated device is not available. 
Vital signs comprise systolic and diastolic BP, pulse rate, and temperature. 
• At Visit 1, 2, 3, 4, 15, and 16, vital signs will be measured prior to IMP administration, at the 
end of the infusion (+5 min) and at 2 hours after the end of infusion (±15 min). 
• At Visit 5, 6, 7, 17, 18, and 19, vital signs will be measured prior to IMP administration and 
1 hour after the end of infusion (±15 min). 
• From Visit 8 through Visit 14 and from Visit 20 through Visit 28, the vital signs will be 
measured approximately 15 minutes prior to IMP administration. 
• At Screening, EOT/EW, and SFU/EOS Visits, vital signs will be taken only once during the 
visit. 
8.2.4 
Electrocardiograms 
Single 12-lead ECG will be obtained as outlined in the Schedule of Activities (see Section 1.3) 
using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, 
and QTc intervals. 
All ECG recordings should be taken with the study participant resting in the supine position for 
at least 5 minutes before the recording. 
The ECGs will be read locally. All ECG readings from an individual study participant should be 
read by the same reader, if possible. Findings will be recorded in the eCRF. 
8.2.5 
Clinical safety laboratory assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and to the 
Schedule of Activities (Section 1.3) for the timing and frequency. 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the study participant's condition. 
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All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated until the values return to normal or Baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
If such values do not return to normal/Baseline within a period of time judged reasonable by the 
investigator, the etiology should be identified and the sponsor notified. 
All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), must be 
conducted in accordance with the Laboratory Manual and the Schedule of Activities. 
If laboratory values from non-protocol specified laboratory assessments performed at the 
laboratory require a change in study 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 source data. 
8.2.6 
Suicidal risk monitoring 
Study participants being treated with IMP should be monitored appropriately for suicidal 
ideation and behavior or any other unusual changes in behavior. Consideration should be given 
to discontinuing IMP in study participants who experience signs of suicidal ideation or behavior. 
Families and caregivers of study participants being treated with IMP should be instructed to 
monitor study participants for the emergence of unusual changes in behavior, as well as the 
emergence of suicidal ideation and behavior, and to report such symptoms immediately to the 
study investigator. 
Suicidality will be assessed by trained study personnel using the C-SSRS (Columbia University 
Medical Center, 2008). This scale will be used for screening as well as to assess suicidal ideation 
and behavior that may occur during the study. The C-SSRS will be performed at the scheduled 
timepoints as described in the Schedule of Activities (Section 1.3). 
8.3 
Adverse events and serious adverse events 
The definitions of an AE or SAE can be found in Appendix 3 (Section 10.3). AEs will be 
reported by the study participant (or, when appropriate, by a caregiver, surrogate, or the study 
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 
study participant to discontinue study treatment or the study (see Section 7). 
For results disclosure on public registries (eg, ClinicalTrials.gov), TEAEs and 
treatment-emergent SAEs will be published. 
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 EOS Visit at the time 
points specified in the Schedule of Activities (Section 1.3). 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the CRF even if no study medication was taken but specific study 
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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). 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 study participant, and to also 
inform study 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. 
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 study 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 study 
participant at subsequent visits/contacts. All SAEs and AESMs (as defined in Section 8.3.7) will 
be followed until resolution, stabilization, the investigator determines that it is no longer 
clinically significant, the event is otherwise explained, or the study 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 of an SAE by the investigator to the sponsor is essential so that legal 
obligations and ethical responsibilities towards the safety of study participants and the safety of a 
study treatment under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Independent Ethics Committees (IEC), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 
An investigator who receives an investigator safety report describing an 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. 
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8.3.5 
Pregnancy 
Details of all pregnancies in female study participants and, if indicated, female partners of male 
study participants will be collected after the start of study treatment and until 90 days after the 
final dose. 
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 study participant should be withdrawn from the study as soon as pregnancy is known (by 
positive pregnancy test), and the following should be completed: 
• The study participant should not receive further doses of IMP. 
• The study participant should return for an EW Visit scheduled as soon as possible, but no 
later than the next scheduled visit. 
• The study participant must be withdrawn from the study (Section 7.2.1). 
• An SFU or EOS Visit should be scheduled 6 weeks after the study participant has 
discontinued her study medication. 
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 (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: 
• Hy’s Law 
− Potential Hy’s Law, defined as ≥3x ULN ALT or AST with coexisting ≥2xULN total 
bilirubin (35% direct bilirubin) in the absence of ≥2xULN ALP, with no alternative 
explanation for the biochemical abnormality (ie, without waiting for any additional 
etiologic investigations to have been concluded). Follow-up information should be 
reported if an alternative etiology is identified during investigation and monitoring of the 
study participant. 
This AESI will follow the SAE recording and reporting procedures as indicated in Appendix 3 
(Section 10.3). 
8.3.7 
Adverse events of special monitoring 
An AE of special monitoring is a product-specific AE, adverse reaction, or safety topic requiring 
special monitoring by UCB. 
For rozanolixizumab, AESMs that require immediate reporting (within 24 hours regardless of 
seriousness) to UCB are: 
• Severe headache and/or serious headache 
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• Suspected aseptic meningitis 
All AESM will follow the SAE recording and reporting procedures as indicated in Section 10.3 
(Appendix 3) and the AESM recording and reporting procedures as indicated in Section 10.13 
(Appendix 13). 
Additionally, protocol guidance for management of hypogammaglobulinemia/infection and 
infusion and hypersensitivity reactions is provided in Section 10.14 (Appendix 14) and 
Section 10.15 (Appendix 15), respectively.  
Although hypersensitivity reactions including infused-related reactions and anaphylaxis are not 
classified as AESM, these AEs will be monitored by the investigator. If such an event is 
suspected it should be managed according to the guidance provided in Section 10.15 
(Appendix 15). Suspected anaphylactic reactions should be diagnosed using Sampson’s Criteria 
(Sampson et al, 2006). 
 
8.3.8 
Anticipated serious adverse events 
The anticipated SAEs in Table 8-1 are anticipated to occur in the population studied in this 
protocol at some frequency that is independent of drug exposure. 
This list does not change the investigator’s obligation to report all SAEs (including anticipated 
SAEs) as detailed in Section 8.3.1 and Appendix 3 (Section 10.3). 
Table 8-1: 
Anticipated serious adverse events for FMS population 
MedDRA System Organ Class 
MedDRA Preferred Term 
Psychiatric disorders 
Abnormal behavior, anxiety, cognitive 
disorder, confusional state, psychotic 
behavior, sleep disorder and disturbances 
Gastrointestinal disorders 
Abdominal pain 
General disorders and administration site 
conditions 
Pain 
Nervous system disorders 
Headache 
MedDRA=Medical Dictionary for Regulatory Activities 
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 IECs will be informed appropriately and as early as possible. 
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the Patient Safety 
representative. 
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In addition, an SMC will be responsible for monitoring safety data during the study 
(Section 9.7.2). A detailed description of the SMC composition, processes, and responsibilities 
will be provided in a separate SMC charter. 
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. 
8.5 
Treatment of overdose 
Any dose increase of 10% or greater from the assigned dose for each administered dose of IMP 
per week should 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 or treating physician should: 
1. Contact the medical monitor immediately. 
2. Closely monitor the study participant for any AE/SAE or laboratory abnormalities for at least 
5 days. 
3. Obtain a plasma sample for PK analysis and IgG (total and subclasses) within 3 days from 
the date of the overdose if requested by the medical monitor (determined on a case-by-case 
basis). 
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions will be made by the investigator in consultation with the 
medical monitor based on the clinical evaluation of the study participant. 
8.6 
Pharmacokinetics and immunogenicity 
Venous blood samples will be collected for measurement of plasma concentrations of 
rozanolixizumab and the detection of ADA as specified in the Schedule of Activities 
(Section 1.3). 
A sample will be taken for the purpose of assay characterization (eg, ADA cutpoint). For study 
participants withdrawing from the study, a sample should be taken for ADA detection upon 
his/her EW Visit. Instructions for the collection and handling of biological samples will be 
provided by the sponsor. The actual date and time of each sample will be recorded in the eCRF. 
Samples will be used to evaluate the PK of rozanolixizumab or detection of ADA and may be 
used for establishing the assay parameters. Samples collected for analyses of rozanolixizumab 
concentration may also be used to evaluate safety and efficacy aspects related to concerns arising 
during or after the study. 
Study participant confidentiality will be maintained. At visits during which plasma/serum 
samples for the determination of multiple aspects of rozanolixizumab will be taken, one sample 
of sufficient volume can be used. 
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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. 
Instructions pertaining to sample collection, processing, storage, labeling and shipping are 
provided in the Laboratory Manual for this study. These samples will be tested by the sponsor or 
the sponsor’s designee. 
8.7 
Pharmacodynamics 
Venous blood samples will be collected at time points specified in the Schedule of Activities 
(Section 1.3) for measurement of total serum IgG and subclass IgG concentrations. 
For all PD assessments, samples will be collected predose. Instructions pertaining to sample 
collection, processing, storage, labeling, and shipping are provided in the Laboratory Manual. 
8.8 
Genetics 
Venous blood samples for potential genetics analyses are part of this study and are described in 
Appendix 5 (Section 10.5). 
8.9 
Biomarkers 
Venous blood samples will be collected to measure IgG binding as an exploratory endpoint; this 
assay is described in Section 8.9.1. Timing of these assessments is provided in the Schedule of 
Activities (Section 1.3). 
Biomarker results will be reported separately from the CSR for this study unless stated 
otherwise. 
Collection of samples for potential future biomarker research to address questions based upon 
evolving science (including companion/complementary diagnostic and general assay 
development/optimization and/or mechanism of action or disease exploration) forms part of the 
study objectives (where biomarkers investigated can include, but are not limited to, DNA, RNA, 
protein, metabolites, and cells). Details on processes for collection and shipment of these 
samples can be found in the Laboratory Manual. 
The following samples will be collected from all study participants and stored to support 
potential future biomarker research. These samples are a required component of the protocol as 
specified in the Schedule of Activities (Section 1.3): 
• Venous blood sample for DNA isolation for genetic/epigenetic analysis. 
Additional biomarker samples: 
• For exploratory biomarkers, 10mL blood samples will be collected for future research into 
biomarkers of some or all of the following: diagnosis, pharmacodynamic effects, disease 
monitoring, response prediction, prognosis, and/or safety. 
If not used immediately, the samples are planned to be stored at -80°C for up to 20 years to allow 
for future exploratory analyses. These samples will be used to further the understanding of FMS 
and related disease conditions, and/or how biomarkers (including genetic variation 
[Section 10.5]) may affect response or safety, or be affected by treatment with rozanolixizumab 
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and comparators, and/or background products and concomitant medications in the treatment of 
FMS. 
8.9.1 
In vitro IgG binding assay 
At Visit 3 (Day 1), 80mL of whole blood will be collected. At subsequent scheduled 
assessments, 10mL of whole blood will be collected for the determination of IgG binding in an 
exploratory in vitro cell assay. These data will be collected for an exploratory endpoint. If not 
used immediately, the samples are planned to be stored at -80°C for up to 20 years to allow for 
future exploratory analyses. 
8.9.2 
Immunology 
Blood samples for immunological testing are required and will be collected from all study 
participants in this study as specified in the Schedule of Activities (Section 1.3) for measurement 
of: 
• Serum complement (C3, C4) 
• Plasma complement (C3a, C5a) 
Samples for serum complement (C3, C4) and plasma complement (C3a, C5a) are collected 
predose at Visit 3 (Day 1) for all study participants. In study participants who experience an 
infusion reaction or hypersensitivity reaction at site, samples should also be taken 2 hours post 
event and 4 hours post event, or otherwise as soon as possible but prior to the next dosing. In 
study participants who experience severe and/or serious headaches or suspected aseptic 
meningitis, additional blood samples should also be taken 4 hours after the onset of the event; or 
otherwise as soon as possible within 72 hours, but prior to next dose. These samples may be 
tested for exploratory biomarkers such as proteins and metabolites to evaluate their association 
with the cause, progression, and appropriate treatment of fibromyalgia. Details on genetic 
analysis are described in Appendix 5 (Section 10.5). 
8.10 
Health economics 
Health economics 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). 
9.1 
Definition of analysis sets 
The following analysis sets have been defined for this study: 
All Study Participants Set: The All-Study Participants Set (ASP) consists of all study participants 
that sign the informed consent form. This set includes screening failures. 
Randomized Set: The Randomized Set (RS) will consist of all participants randomized into the 
study. 
Safety Set – as Randomized: The Safety Set as randomized (SS-r) consists of all study 
participants who received any study treatment, including during the run-in period. The study 
participants will be analyzed according to the randomized treatment groups during the specific 
treatment period. 
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The SS-r will be used for production of safety analysis by visit, as well as demographics and 
immunogenicity analyses. 
Safety Set – as Treated: The Safety Set as treated (SS-t) consists of all study participants who 
received any study treatment including during the run-in period. If a participant received at least 
one dose of active treatment during a given treatment period, participant will be allocated to 
active treatment group at the given treatment period and any period thereafter in the SS-t as 
treated analysis set (most conservative approach). For analysis purposes, the SS-t will be used for 
tabulating AEs by treatment where AEs are assigned to the active treatment group based on the 
onset of AE relative to the first dose of active treatment. 
The SS-t will be used for safety overall analysis. 
Full Analysis Set: The Full Analysis Set (FAS) consists of all study participants in the SS-r who 
have a Baseline value and at least one post-Baseline efficacy endpoint assessment. Study 
participants who receive at least one dose of treatment not per randomization schedule will be 
excluded from the FAS. 
This analysis set will be used for the summaries and analyses of primary, secondary, and 
exploratory efficacy variables data. 
Pharmacokinetic Set: The Pharmacokinetics Set (PKS) consists of all study participants in the 
SS-r who have at least one dose of active IMP and at least one measurable PK concentration 
including below limit of quantification (BLQ). The PKS will be used for all PK summaries and 
analyses. If a study participant in the PKS is missing individual time points or are otherwise 
unobservable, they will be included in the PKS but those time points will be omitted from the PK 
summaries, as appropriate. 
Pharmacodynamic Set: The Pharmacodynamic set (PDS) is a subset of the FAS, 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, and who had at least 
one valid post-Baseline measurement of serum total IgG and IgG subclasses. The final PDS will 
be identified after database lock to confirm availability of at least one post-Baseline valid 
measurement due to blinding. The PDS will be used for all PD summaries and analyses. 
Participants who had important protocol deviations affecting the relevant efficacy/PK/PD 
variables, as confirmed during a pre-analysis review of the data prior to database lock might be 
excluded from relevant analyses. Such exclusions will be described in tables, figures, and listings 
(TFLs) and/or the CSR. 
9.2 
General statistical considerations 
All TFLs, including statistical evaluation, will be using SAS version 9.4 or higher (SAS Institute, 
Cary, North Carolina, USA). Analysis data will adhere to Clinical Data Interchange Standards 
Consortium (CDISC) guidance documents for Analysis Data Model (ADaM) and follow the 
UCB interpretation. 
The Baseline for each variable will be taken as the value measured prior to, but closest to, the 
treatment on Day 1. This may be measured on Day 1 prior to treatment or during Weeks -1 or -2 
depending on the endpoint. 
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Summary TFLs will be presented by sequence and by period (Period 1, Period 2 or SFU), as well 
as by treatment, and period. For continuous variable summaries for the study participant-level 
difference between Period 2 and Period 1 by sequence will also be presented. Listings will be 
presented by study participant and treatment sequence. In addition, summaries by visit may be 
presented where appropriate. 
Data will also be summarized graphically by sequence, treatment, and time as appropriate. All 
clinical outcome data will be listed, and additional exploratory statistical analysis may be 
conducted. 
1) Categorical Variables 
Categorical variables will be summarized using frequency counts and percentages. Unless 
otherwise stated, the denominator for the percentage calculations will be based on the number of 
study participants in the respective analysis set, treatment group, visit and timepoint (as 
applicable) with non-missing data 
2) Continuous Variables 
Summary statistics will be presented for continuous variables including number of study 
participants (n), mean, standard deviation (SD), median, minimum and maximum. Geometric 
mean (geoMean), geometric coefficient of variation (geoCV) and 95% CI for the geoMean will 
also be presented in the summaries of rozanolixizumab concentration data. 
When reporting descriptive statistics, the following rules will apply in general: 
• Mean (arithmetic and geometric), SD and median will use 1 decimal place more, or 1 
significant figure more –– than the original data 
• Confidence intervals will use 1 decimal place more, or 1 significant figure more – depending 
on the reporting format of the original data – than the value around which the confidence 
interval is constructed 
• Coefficient of variation will be reported as a percentage to 1 decimal place 
• Minimum and maximum will be reported using the same number of decimal places or 
significant figures as the original value 
• If no study participants have data at a given time point, then only n=0 will be presented. If 
n<3, then only the n, minimum and maximum will be presented. If n=3, then only n, 
minimum, median and maximum will be presented. The other descriptive statistics will be 
left blank. 
9.3 
Planned efficacy/outcome analyses 
9.3.1 
Analysis of the primary efficacy/primary endpoint 
The primary endpoint is the average BPI-SF interference score after 12 weeks of double-blind 
treatment, adjusted for Baseline score (see also Section 4.1 on Study Design). 
For the purpose of analysis, there will be three treatment groups: placebo, rozanolixizumab for 
up to 12 weeks, or rozanolixizumab given beyond 12 weeks [Sequence 1, Period 2]. The main 
difference of interest is that between rozanolixizumab for up to 12 weeks and placebo. 
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In order to estimate the mean difference in the average BPI-SF interference scores after 12 weeks 
of treatment, the BPI-SF interference scores measured at Visits 7, 11, 15, 19, 23, and 27 will be 
modelled using a longitudinal linear mixed effect model (LMM). The pre-dose value taken at the 
first visit of Period 2 (Visit 15) will be used as the measure of treatment effect after 12 weeks of 
treatment for Period 1, while the pre-dose value taken at run-out Visit 27 will be used as the 
measure of treatment effect after 12 weeks of treatment for Period 2. 
Treatment will be a fixed effect and the study participant ID will be included as a random effect. 
The following additional fixed effects will be included: 
• treatment period (period 1 or period 2) 
• assessment number within the period (1st, 2nd, or 3rd assessment corresponding to Visit 7, 11, 
and 15 for Period 1, or Visit 19, 23, or 27  for Period 2) 
• an interaction of treatment by assessment number 
• an interaction of treatment period by assessment number 
The following covariates will also be included: 
• BPI-SF interference scores at Baseline (taken at Visit 3, prior to dosing) 
Other covariates may be included if considered appropriate. 
The model result of interest will be the marginal estimated mean treatment difference in average 
BPI-SF after 12 weeks of treatment. 
All study participants in the FAS with Baseline BPI-SF score and one or more post-Baseline 
assessments will be included in the model. 
As secondary analysis strategy, each period will be analyzed separately using a mixed effect 
model, with study participant as random effect and treatment, assessment number, treatment by 
assessment number interaction, Baseline, Baseline by assessment number and site as fixed 
effects. 
For Period 1, there will be 2 treatment groups: placebo and rozanolixizumab. For Period 2, there 
will be 3 as defined for the primary analysis. Additional analyses will be described in the SAP. 
9.3.1.1 
Estimand/ICE handling rationale and impact on the study 
The primary estimand (as described in Section 3) has been chosen to best reflect the goal of 
identifying a treatment effect of rozanolixizumab for FMS. FMS is a highly prevalent (2 to 3% 
of adult population) and complex syndrome primarily characterized by the presence of chronic 
widespread pain, but which also incorporates a wide range of other symptoms adversely 
impacting on function and quality of life such as severe fatigue, cognitive dysfunction, and sleep 
disturbances (Häuser et al, 2015). The BPI-SF interference score measures the impact of pain 
across seven domains of daily life experience and was considered as being suitable for measuring 
the effect of a treatment and the functional interference experienced by patients. 
The main ICE of interest is treatment discontinuation. The chosen Hypothetical strategy of ICE 
handling whereby data following discontinuation is excluded from analysis reflects the focus on 
demonstrating efficacy rather than effectiveness, and thus estimating the treatment effect in an 
ideal condition where such events would not occur. 
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9.3.2 
Secondary efficacy analyses 
Analyses of the following secondary efficacy endpoints will be conducted using an LMM in the 
same way as for the primary estimand analysis, using the same ICE strategies: 
• FIQR score after 10 weeks of treatment 
• Mean 7-day average pain score (Pain NRS) after 10 weeks of treatment 
• Mean 7-day fatigue score (Fatigue NRS) after 10 weeks of treatment  
However, for these endpoints, the value taken at/subsequent to Week 11 (Visit 13) will be used 
as the measure of treatment effect after 10 weeks of treatment for Treatment Period 1, while the 
value taken at/subsequent to Week 23 (Visit 25) will be used as the measure of treatment effect 
after 10 weeks of treatment for Treatment Period 2. The data collected at Run-in Visit 2, 
Week -1, will be used as Baseline values. Note that for the Pain NRS and Fatigue NRS, the 
subject will be asked at Visit 13 and Visit 25 to fill in their diary for that day and every day for 
the following 6 days, and the average of these 7 measurements will be taken as the endpoint. 
For the BPI-SF interference scores and these scores, the mean scores will be plotted over time 
for each sequence. For the BPI-SF interference score, the values after 12 and 24 weeks from 
Sequence 1 and 3 will be analysed to estimate treatment effects after 24 weeks and compare this 
with 12 weeks. The data will be analysed using a mixed effect model with a random study 
participant effect and fixed effects for treatment, week and treatment by week interaction, 
Baseline and Baseline by week interaction. The same ICE strategies will be used as in the 
12-week analysis. 
9.3.3 
Other efficacy/other outcome analyses 
As a secondary analysis strategy, dropouts will be imputed as if they belong to the placebo 
group, under the conservative assumptions that dropouts are due to a lack of drug efficacy. 
Details on the imputation will be provided in the SAP. 
Exploratory endpoints will be summarized and represented graphically where relevant. Due to 
the exploratory nature of this study, additional analyses may be completed to further understand 
any findings. 
9.4 
Planned safety and other analyses 
9.4.1 
Safety analyses 
All safety variables will be analyzed by descriptive methods and presented by sequence and by 
period (Period 1, Period 2, or SFU) showing the treatment when the safety event occurred. In 
addition, events will be summarized by treatment and period. Any events in the SFU Period from 
sequence 1 and 2 will be tabulated under active treatment. 
• Frequency and intensity of TEAEs from Baseline to SFU, and 
• TEAEs leading to withdrawal of IMP 
will be the safety variables analyzed in this study and will be included in the summary tables. 
The overall frequency during the study period will be presented for each of the safety variables, 
as well as separately by System Organ Class, high level term, and preferred term (Medical 
Dictionary for Regulatory Activities [MedDRA®]). The data will be displayed as number of 
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study participants experiencing the event, percentage of study participants, and number of 
events. Additional tables will summarize the safety variables by maximum intensity, by 
intensity, and by relationship to study drug. 
Laboratory evaluations and vital signs will be analyzed over time. Possibly clinically significant 
treatment-emergent abnormalities will be listed and summarized by visit for each treatment 
group. 
9.4.2 
Other analyses 
9.4.2.1 
PK analyses 
Plasma concentration data of rozanolixizumab will be summarized by treatment group, actual 
dose received, and time point using the number of available observations, mean, median, SD, 
minimum, maximum, geometric mean (and associated 95% confidence intervals), and geoCV 
(assuming log-normally distributed data). Values below the 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). However, 
minimum and maximum will always be reported even if <2/3 are quantifiable; minimum should 
be reported as value of LLOQ where it is not above this value. 
9.4.2.2 
Immunogenicity analyses 
A tiered ADA approach will be used for this study. Samples will first be evaluated in the 
screening assay using a false positivity rate of 5% (reported as negative screen or positive 
screen), followed by analysis of screened positive samples in the confirmatory assay (which is a 
drug depletion assay) to confirm the true positivity of the samples (reported as negative 
immunodepletion or positive immunodepletion). Samples that are confirmed as positive will be 
evaluated in a titration assay to quantify the ADA level and will be reported as titer (reciprocal 
dilution factor including minimum required dilution). For ADA positive immunodepletion 
samples (or subset of), further characterization for neutralizing ADA potential in vitro will be 
performed. Results will be presented in a listing and as summary tables with full details provided 
in the SAP. 
9.4.2.3 
PD analyses 
For all PD variables, descriptive statistics for the value, change from Baseline, and/or percentage 
change from Baseline will be tabulated by treatment group, actual dose received, and time point. 
The PD variables will include serum total IgG and IgG subclass concentrations. 
9.4.2.4 
Immunological analyses 
All immunologic variables including serum (C3 and C4) and plasma (C3a and C5a) complement 
levels will be summarized by treatment group and visit using descriptive statistics. 
9.5 
Handling of protocol deviations 
Important protocol deviations (IPDs) are a subset of protocol deviations that may significantly 
impact the completeness, accuracy, and/or reliability of the study data (primary or key secondary 
outcomes) or that may significantly affect a subject's rights, safety, or well-being. 
The criteria for identifying such protocol deviations will be defined within the IPD specifications 
document. 
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Important protocol deviations will be categorized as follows: 
• Inclusion/exclusion criteria deviations 
• Incorrect treatment or dose administered 
• Procedural non-compliance 
• Prohibited concomitant medication use  
• Withdrawal criteria deviation  
All IPDs will be reviewed as part of the ongoing data cleaning process and data evaluation. At 
least one Data Evaluation Meeting (DEM) will be performed prior to the final database lock after 
all data have been verified/coded/entered into the database. All protocol deviations will be 
discussed at the DEM and decisions made on whether they should be considered important or 
not. Important protocol deviations will be identified and classified by the deviation types in the 
IPD document. 
IPDs identified at the DEM will be listed and summarized by treatment sequence and period for 
the SS and will include the deviation type and description. 
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 
9.7.1 
Interim analysis 
After approximatively 30 study participants have been randomized and these study participants 
have completed their 2 treatment periods, an interim analysis may be conducted where the 
primary endpoint and some of the secondary and exploratory endpoints may be analyzed. The 
timing of the interim analysis may be changed depending on recruitment rates to allow for an 
earlier analysis. It may also be decided not to perform the interim analysis. The purpose of this 
interim analysis is to provide results to trigger regulatory discussions, aid Phase 3 planning, and 
investigate some of the exploratory endpoints. The outcome of this interim analysis may lead to 
stopping the study for futility if there is a >75% posterior probability that the reduction in mean 
BPI-SF interference score is below 0.5 when treated with rozanolixizumab compared with 
placebo or stopping for efficacy if >90% posterior probability that the reduction in mean score is 
greater than 1 (using a Bayesian interpretation of the results with a non-informative prior). If a 
futility or efficacy decision is not reached, the study will continue. The interim decision criteria 
will be described in the SAP for the interim and in the interim charter. 
In addition, at the interim analysis, the observed dropout rate and observed within/between 
variability will be evaluated, and a recommendation on whether to adjust the overall sample size 
may be provided. 
The interim analysis will be completed by an independent, internal, Interim Analysis Group 
(IAG) who will be unblinded to the randomization and treatment allocation. The study team will 
remain blind to the treatment allocation until database lock at the end of the study. The 
composition of the IAG will be specified in an IAG charter. 
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The recommendation of the IAG will be presented to selected senior stakeholders who will make 
the final decision of stopping or continuing the study, and whether to adjust the sample size. The 
IAG charter will specify the senior stakeholders to be informed, and will also contain a 
communication plan setting out what information will be presented to the senior stakeholders, to 
the wider study team and what will be presented to other audiences. 
9.7.2 
Data monitoring 
An internal SMC will regularly review (approximately every 3 months, with the option to adapt 
the frequency based on recruitment rates) the available blinded safety data. If required, a “closed 
session” may be instituted to allow the review of unblinded data.  
If there are safety concerns during the SMC session, an ad hoc closed SMC meeting may be 
called if revealing treatment allocation would aid decision making. The members of closed SMC 
sessions will be restricted and specified in the SMC charter. 
The first SMC review will be conducted approximately 2 months after randomization of the first 
study participant, or when 25% of the study participants are randomized, whatever comes first. 
The SMC will decide if the study is safe to continue. 
In addition, a Program Independent Data Monitoring Committee (PiDMC) is in place to evaluate 
data over the entire rozanolixizumab clinical development program as this molecule is being 
investigated in several indications. Details of the PiDMC composition, procedures, and 
responsibilities are detailed in the PiDMC charter.  
9.8 
Determination of sample size 
The operating characteristics of the design were evaluated using a simulation approach and based 
on estimates of variability and treatment effects from fibromyalgia studies reported in 
clinicaltrials.gov and other papers. BPI-SF was used consistently in duloxetine studies. A sample 
size of 48 completed study participants gives more than 80% probability that if the true 
difference of the mean BPI-SF interference score after 12 weeks of treatment on 
rozanolixizumab compared with placebo was 1.0 units or better, then the comparison would pass 
a 1-sided 10% significance test. This assumes a between-study participant standard deviation 
component for the BPI-SF interference score of 1.74 units, and a within-study participant SD of 
1.5 units (a total between-study participant SD of 2.3 units) after accounting for the Baseline 
BPI-SF interference score. It is assumed that the dropout rate will be 25% also estimated for the 
study results. Through simulations using the design, it was estimated that 60 study participants 
starting the study would achieve the desired power. 
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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)-Good Clinical Practice (GCP), and in accordance 
with the ethical principles that have their origin in the Declaration of Helsinki. 
The investigator/UCB will ensure that an appropriately constituted IEC that complies with the 
requirements of the current ICH-GCP version or applicable country-specific regulations will be 
responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the investigator/UCB will forward copies of the protocol, ICF, IB, 
investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all other study 
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 study participants or others, and any protocol deviations, to eliminate 
immediate hazards to study 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 study 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 study 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 
Study 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 study participant in both oral and written form by the 
investigator (or designee). Each study participant will have the opportunity to discuss the study 
and its alternatives with the investigator. 
Prior to participation in the study, the ICF should be signed and personally dated by the study 
participant and by the person who conducted the informed consent discussion (investigator or 
designee). The study participant or his/her legal representative must receive a copy of the signed 
and dated ICF. As part of the consent process, each study participant must consent to direct 
access to his/her medical records for study-related monitoring, auditing, IEC review, and 
regulatory inspection. 
If the ICF 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 ICF by 
the IEC and use of the amended form. 
The study participant may withdraw his/her consent to participate in the study at any time. A 
study participant is considered as enrolled in the study when he/she has signed the ICF. A CRF 
must not be started, nor may any study specific procedure be performed for a given study 
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 study participant’s confidentiality. 
Throughout this study, all data forwarded to UCB (or designee) will be identified only by the 
study 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 
study 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 study participant’s study participation, and autopsy 
reports for deaths occurring during the study). 
The study 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 study participant. 
The study 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 
As described in Section 9.7.2, an internal SMC will be established to regularly review available 
blinded safety data, and if required, a SMC “closed session” may be instituted to allow the 
review of unblinded data. 
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An internal SMC will be established and will comprise key sponsor personnel and coordinating 
investigator at the CRO. The SMC will operate in the setting of a PiDMC that has been 
established as an independent panel of external experts whose principal responsibilities are to 
review and evaluate on a regular basis pooled cumulative data overall across the 
rozanolixizumab program and by indication. The PiDMC has access to unblinded data with 
appropriate safeguards in place for maintaining the blind with respect to the investigators, site 
monitors and UCB Rozanolixizumab Program Team (including extended members and study 
teams). The operation of the SMC and PiDMC and the roles and responsibilities of committee 
members are described in their respective charters.  
10.1.6 
Data quality assurance 
All study participant data relating to the study will be recorded on printed or electronic CRF 
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 CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
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 CRF by authorized site personnel are accurate, legible, contemporaneous, original, and 
attributable from source documents; that the safety and rights of study 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. 
Quality tolerance limits may be established for the study using parameters related to patient 
safety reporting and reliability of study results. If limits are stablished, the parameters will be 
monitored throughout the study to identify systematic issues. Parameters used, parameter values, 
important deviations from the quality tolerance limits, and actions taken will be summarized in 
the clinical study report. 
10.1.6.1 
Case report form completion 
The investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
eCRFs and in all required reports. 
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change. 
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Corrections made after the investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the investigator. 
The investigator should maintain a list of personnel authorized to enter data into the electronic 
CRF. 
Detailed instructions will be provided in the CRF 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, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies and/or printouts of CRFs are not considered 
acceptable source documents. 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, quality of life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area. 
The following data will be recorded directly in the electronic device and will not appear in a 
source document as defined above: 
• Pain NRS 
• BPI-SF 
• FIQR 
• Fatigue NRS 
A list of source data will be provided in a separate document (Source data agreement). 
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 study 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. 
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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 study 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 central laboratory.  
• Protocol-specific requirements for inclusion or exclusion of study participants are detailed in 
Section 5.1 and Section 5.2 of the protocol. 
• Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations. 
• 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, unless a safety alert 
requires a clinical review of the study participant. 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
RBC Indices: 
Mean corpuscular volume 
(MCV) 
Mean corpuscular 
hemoglobin (MCH) 
%Reticulocytes 
WBC Count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistrya 
Urea 
Potassium 
Aspartate Aminotransferase 
(AST)/Serum Glutamic-
Oxaloacetic Transaminase 
(SGOT) 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
Alanine Aminotransferase  
(ALT)/Serum Glutamic-
Pyruvic Transaminase (SGPT) 
Total proteinb 
Albuminb 
 
Random 
Glucose 
Calcium 
Alkaline phosphatase 
 
 
Lactate 
dehydrogenase 
(LDH) 
C-reactive 
protein 
(CRP) 
Low-density lipoprotein (LDL) 
High-density lipoprotein 
(HDL) 
Total cholesterol 
Triglycerides 
 
Routine 
Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Other Screening 
Tests 
• 
Follicle-stimulating hormone and estradiol (as needed in WOCBP only) 
• 
Serum human chorionic gonadotropin pregnancy test (as needed for WOCBP) 
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Laboratory 
Assessments 
Parameters 
• 
Serology testing for Hepatitis B surface antigen, Hepatitis C virus antibody, 
and human immunodeficiency virus. 
• 
IGRA TB test (if applicable, as this test is optional) 
All study-required laboratory assessments will be performed by a central laboratory, 
with the exception of: 
− 
Urine pregnancy dipstick testc 
− 
Urine drug screen 
eCRF=electronic case report form; IEC=Independent Ethics Committee; IGRA= interferon gamma release assay 
INR=international normalized ratio; RBC=red blood cell; SAE=serious adverse event; TB=tuberculosis; 
ULN=upper limit of normal; WBC=white blood cell; WOCBP=woman of childbearing potential 
The results of each test must be entered into the eCRF. 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver  stopping 
or monitoring event are given in Section 10.6 (Appendix 6). All events of ALT 3xULN and bilirubin 2xULN 
(>35% direct bilirubin) or ALT 3xULN and INR>1.5, if INR measured, may indicate severe liver injury 
(possible Hy’s Law) and must be reported as an SAE (excluding studies of hepatic impairment or cirrhosis). 
b The results of these assessments will not be reported to investigative sites or other blinded personnel until the 
study has been unblinded, unless a safety alert requires a clinical review of the study participant. 
c Urine testing will be standard for the protocol unless serum testing is required by local regulation or IEC. 
Investigators must document their review of each laboratory safety report. 
Other protocol-required laboratory assessments 
Laboratory 
Assessments 
Parameters 
Other laboratory 
assessments 
• 
Blood sampling for PK of rozanolixizumaba 
• 
Blood sampling for DNA and RNA analysisb 
• 
Serum complement (C3, C4), and plasma complement (C3a, C5a)b 
• 
Total IgGa 
• 
IgG subclassesa 
• 
Anti-drug antibodiesa 
• 
Blood sampling for exploratory biomarker analysisb  
C3=complement component 3; C3a=complement component 3a; C4=complement component 4; C5a=complement 
component 5a; Ig=immunoglobulin; PK=pharmacokinetics 
a The results of these assessments will not be reported to investigative sites or other blinded personnel until the 
study has been unblinded, unless a safety alert prompts a clinical review of the study participant. 
b The results of these assessments will not be reported to investigative sites. 
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10.3 
Appendix 3: Adverse events – Definitions and procedures for 
recording, evaluating, follow-up, and reporting 
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 measurements), including those that worsen 
from Baseline, considered clinically significant in the medical and scientific judgment of the 
investigator (ie, not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition, including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after 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. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as 
an AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE 
if they fulfill the definition of an AE or SAE. 
 
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Events NOT meeting the AE definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the investigator to be more 
severe than expected for the study participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the study participant’s 
condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 
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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). 
An 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 study 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 study 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 study participant or 
may require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
• 
Examples of such events include, but are not limited to, potential Hy’s law, invasive or 
malignant cancers, intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
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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 CRF. 
• 
It is not acceptable for the investigator to send photocopies of the study participant’s medical 
records to UCB in lieu of completion of the UCB/AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all study participant identifiers, with the exception of the study 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 study participant, causing minimal discomfort and 
not interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with an SAE. Severe is a category utilized for rating the intensity of an 
event; and both AEs and SAEs can be assessed as severe. 
• 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe (eg, a severe AE may be 
either serious or not serious, depending on whether these criteria are also met). 
The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 
should be used as a supportive standardization instrument to evaluate AEs and SAEs but the final 
intensity grading by the investigator must be mild, moderate, or severe. 
 
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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 (IB) and/or Product Information, 
for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to UCB. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to UCB. 
• 
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one 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 study participant is lost to follow-up. 
This follow-up requirement applies to AEs, SAEs, and AEs of special interest. 
• 
If a study participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide UCB with a copy of any post-mortem findings including 
histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The investigator will submit any updated SAE data to the sponsor within 24 hours of receipt of 
the information. 
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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) or to the UCB by 
telephone. 
• 
Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING. 
 
SAE reporting to UCB via paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to UCB; see SERIOUS ADVERSE EVENT REPORTING. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service. 
• 
Initial notification via telephone does not replace the need for the investigator to complete and 
sign the SAE CRF pages within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING. 
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10.4 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
Definitions 
Woman of childbearing potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 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 study participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
− A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 
− Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception guidance 
Female participants 
Female study 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 the table 
below. 
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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 
ovulation 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 
Highly effective methods that are user independentc 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
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 WOCBP 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 study participant. 
NOTES: 
a) In case of newly started contraception pills/IUDs, the 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 study participants participating in clinical 
studies. 
Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test. 
• Additional pregnancy testing should be performed as specified in the Schedule of Activities 
(Section 1.3) and as required locally. 
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
• Pregnancy testing, with a sensitivity of 25mIU/mL will be performed. 
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Female participants who become pregnant 
• Any female study participant who becomes pregnant while participating in the study will be 
withdrawn from the study. 
• The investigator will collect pregnancy information on any female study 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 study 
participant's pregnancy. The study participant will be followed to determine the outcome of 
the pregnancy. The investigator will collect follow-up information on the study 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. 
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 rozanolixizumab. If the 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 one working day of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-
up will be at least 12 months after the delivery date. Any termination of the pregnancy will 
be reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
 
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10.5 
Appendix 5: Genetics 
Use and analysis of DNA 
• Genetic variation may impact a study participant’s response to study medication, 
susceptibility to, and severity and progression of disease. Variable response to study 
medication may be due to genetic determinants that impact drug absorption, distribution, 
metabolism, and excretion; mechanism of action of the drug; disease etiology; and/or 
molecular subtype of the disease being treated. Therefore, where local regulations and IEC 
allow, a blood sample will be collected for DNA analysis from consenting study participants. 
• DNA samples will be used for research related to rozanolixizumab and/or FMS and related 
diseases. They may also be used to develop tests/assays, including diagnostic tests related to 
rozanolixizumab /or interventions of this drug class and FMS. Genetic research may consist 
of the analysis of one or more candidate genes or the analysis of genetic markers across the 
entire genome (as appropriate), but only as they relate to the aims of further understanding 
the response to rozanolixizumab and FMS. 
• The samples may be analyzed as part of this study alone or as part of a multi-study 
assessment of genetic factors involved in FMS and the response to rozanolixizumab or study 
medications of this class, and to understand the disease or related conditions. 
• The results of genetic analyses may be reported in the CSR or in a separate study summary. 
• The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality. 
• The samples will be retained while research on FMS continues but no longer than 20 years or 
other period as per local requirements. 
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10.6 
Appendix 6: Liver safety – suggested actions and follow-up 
assessments 
Study participants with PDILI must be assessed to determine if study medication must be 
discontinued. In addition, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. 
Investigators should attempt to obtain information on study participants in the case of study 
medication discontinuation to complete the final evaluation. 
Study participants with PDILI should not be withdrawn from the study until investigation and 
monitoring are complete. All results of these evaluations and observations, as well as the 
reason(s) for study medication discontinuation and/or study 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 >3xULN. The monitoring plan should include 
any necessary follow-up assessments (until resolution of the abnormal laboratory values). 
Phase 2 liver chemistry stopping criteria are designed to assure study participant safety and to 
evaluate liver event etiology. They are presented in the tables below. 
Table 10-2: Phase 2 liver chemistry stopping criteria and follow-up 
assessments 
Liver chemistry stopping criteria 
ALT-absolute 
ALT 5x ULN 
ALT increase 
ALT 3xULN persists for 4 weeks 
Bilirubina,b  
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) 
INRb 
ALT 3xULN and INR >1.5, if INR measured 
Cannot monitor 
ALT 3xULN and cannot be monitored weekly for 4 weeks 
Symptomaticc 
ALT 3xULN associated with symptoms (new or worsening) believed to be related 
to liver injury or hypersensitivity 
Suggested actions and follow-up assessments  
Actions 
Follow-up assessments 
• 
Immediately discontinue study medication. 
• 
Report the event to UCB within 24 hours. 
• 
Complete the liver event CRF, and complete an 
SAE data collection tool if the event also met the 
criteria for an SAE.b 
• 
Perform liver chemistry follow-up assessments. 
• 
Viral hepatitis serologyd 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminase values show downward 
trend 
• 
Obtain blood sample for PK analysis as 
soon as feasible after the most recent 
dosee 
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Table 10-2: Phase 2 liver chemistry stopping criteria and follow-up 
assessments 
Liver chemistry stopping criteria 
• 
Monitor the study participant until liver chemistry 
test abnormalities resolve, stabilize, or return to 
Baseline (see MONITORING). 
• 
Do not restart/rechallenge study participant with 
study medication. 
• 
Permanently discontinue study medication, and 
continue study participant in the study for any 
protocol-specified follow-up assessments 
• 
Consider the need for a toxicology screening 
MONITORING: 
If ALT 3xULN AND bilirubin 2xULN or INR 
>1.5: 
• 
Repeat liver chemistry tests (include ALT, AST, 
ALP, bilirubin) and perform liver event follow-up 
assessments within 24 hours. 
• 
Monitor study participant twice weekly until liver 
chemistry 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 chemistry tests (include ALT, AST, 
ALP, bilirubin) and perform liver chemistry 
follow-up assessments within 24 to 72 hours. 
• 
Monitor study participants weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to Baseline. 
• 
Serum CPK and LDH 
• 
Fractionate bilirubin, if total bilirubin 
2xULN 
• 
Obtain complete blood count with 
differential to assess eosinophilia 
• 
Record the appearance or worsening of 
clinical symptoms of liver injury (eg, 
fatigue, nausea, vomiting, right upper 
quadrant pain), or hypersensitivity, on 
the AE eCRF 
• 
Record use of concomitant medications 
(including acetaminophen [or 
paracetamol], herbal remedies, and other 
over-the-counter medications) on the 
concomitant medications eCRF. 
• 
Record alcohol use on the liver event 
alcohol intake eCRF 
• 
Exclude pregnancy 
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 HPLC 
assay (quantifies potential 
acetaminophen contribution to liver 
injury in study participants with definite 
or likely acetaminophen use in the 
preceding week [James et al, 2009]). 
• 
Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver 
disease; complete liver imaging and/or 
liver biopsy CRFs. 
AE=adverse event; ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
CPK=creatine phosphokinase; CRF=case report form; HBsAg=hepatitis B surface antigen; HBcAb=hepatitis B 
core antibody; HPLC=high performance liquid chromatography; IgG=immunoglobulin G; 
IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate dehydrogenase; 
PK=pharmacokinetic; 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 medication if ALT ≥3xULN and bilirubin ≥2xULN. Additionally, if 
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Table 10-2: Phase 2 liver chemistry stopping criteria and follow-up 
assessments 
Liver chemistry stopping criteria 
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 study participants receiving anticoagulants. 
c New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia). 
d Includes: hepatitis A IgM antibody; HBsAg and HBcAb; hepatitis C RNA; cytomegalovirus IgM antibody; 
Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile antibody or monospot testing); 
and hepatitis E IgM antibody. 
e PK sample may not be required for study 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 dose of study 
medication prior to the blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the 
study 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 IMP Handling Manual. 
 
Table 10-3: Phase 2 liver chemistry increased monitoring criterion with 
continued study medication 
Liver chemistry increased monitoring criterion and follow-up 
Criterion 
Actions 
ALT 3x ULN and <5xULN and 
bilirubin <2xULN, without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 4 weeks 
• 
Notify the UCB medical monitor within 24 hours of 
learning of the abnormality to discuss study 
participant safety. 
• 
Study participant can continue study medication. 
• 
Study participant must return weekly for repeat liver 
chemistry tests (ALT, AST, ALP, bilirubin) until the 
abnormalities resolve, stabilize or return to Baseline. 
• 
If at any time, the study participant meets liver 
chemistry stopping criteria, proceed as described in 
Section 7.1.1. 
• 
If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor study participants twice 
monthly until liver chemistry tests resolve, stabilize, 
or return to Baseline. 
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit 
of normal 
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10.7 
Appendix 7: Medical device AEs, adverse device effects, 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 
Not applicable. 
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10.9 
Appendix 9: Country-specific requirements 
Not applicable. 
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10.10 
Appendix 10: Abbreviations and trademarks 
AChR 
anti-acetylcholine receptor 
ADA 
antidrug antibody 
ADL 
activities of daily living 
AE 
adverse event 
AESI 
adverse event of special interest 
AESM 
adverse event of special monitoring 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BPI-SF 
Brief Pain Inventory-short form 
CIDP 
chronic inflammatory demyelinating polyradiculoneuropathy 
COVID-19 
coronavirus disease 2019 
CNS 
Central nervous system 
CPM 
Clinical Project Manager 
CRF 
case report form 
CRO 
contract research organization 
CSF 
cerebrospinal fluid  
C-SSRS 
Columbia-Suicidality Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
DEM 
Data Evaluation Meeting 
DIAM 
Drug-induced aseptic meningitis 
DRG 
dorsal root ganglia 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOS 
End of Study 
EOT 
End of Treatment 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
EW 
Early Withdrawal 
FAS 
Full Analysis Set 
FcRn 
neonatal Fc receptor 
FIQR 
Revised Fibromyalgia Impact Questionnaire 
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FMS 
fibromyalgia syndrome 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
geoCV 
geometric CV 
geoMean 
geometric mean 
GI 
gastrointestinal 
gMG 
generalized myasthenia gravis 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IAG 
Interim Analysis Group 
IB 
Investigator’s Brochure 
ICE 
intercurrent event 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IGRA 
interferon gamma release assay 
IMP 
investigational medicinal product 
IND 
Investigational New Drug 
IPD 
important protocol deviation 
IRT 
interactive response technology 
ITP 
immune thrombocytopenia 
LLOQ 
lower limit of quantification 
LMM 
linear mixed effect model 
LTBI 
latent tuberculosis infection 
MDRD 
Modification of Diet in Renal Disease 
MG 
myasthenia gravis 
MG-ADL 
myasthenia gravis-activities of daily living 
MOG 
myelin oligodendrocyte glycoprotein antibody 
NRS 
numeric rating scale  
NTM(B) 
nontuberculosis mycobacteria 
OTC 
over-the-counter 
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PD 
pharmacodynamic(s) 
PD-PPS 
Pharmacodynamic Per-Protocol Set 
PDILI 
potential drug-induced liver injury 
PiDMC 
Program Independent  Data Monitoring Committee 
PK 
pharmacokinetic(s) 
PK-PPS 
Pharmacokinetic Per-Protocol Set 
PLEX 
plasma exchange 
prn 
(pro re nata) as needed) 
PRO 
patient-reported outcome 
PV 
pemphigus vulgaris 
QTcF 
QT interval corrected using Fridericia’s formula 
QW 
once weekly 
RS 
Randomized Set 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
sc 
subcutaneous(ly) 
SD 
standard deviation 
SFU 
Safety Follow-up 
SMC 
Safety Monitoring Committee 
SoC 
standard of care 
SS 
Safety Set 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TFL 
Tables, figures, and listings 
ULN 
upper limit of normal 
VAS 
visual analog scale 
WOCBP 
woman of childbearing potential 
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10.11 
Appendix 11: Protocol amendment history 
10.11.1 
Amendment 2 (29 Nov 2022) 
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 reason for this amendment is to update safety information in line with the revised IB dated 
06 September 2022.  
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of activities 
1.3.1 Additional study 
assessments 
2.3 Benefit/Risk 
Assessment 
7.1.2 Other permanent 
discontinuation criteria 
7.1.4 Temporary 
discontinuation 
10.2 Appendix 2: Clinical 
Laboratory Tests 
8.2.2 Neurological 
examination 
8.3.7 Adverse events of 
special monitoring 
8.9.2 Immunology 
10.13 Appendix 13 
Management of Adverse 
Event of Special 
Monitoring 
Removal of the assessments related 
to the former AESM of severe GI 
disorders and opportunistic 
infections. 
Addition of assessments for the 
new AESM of suspected aseptic 
meningitis. 
Removal of the headache 
questionnaire (formerly Appendix 
13) and management of severe 
diarrhoea (formerly Appendix 15).  
New Appendix 13 detailing the 
management of the AESM 
(severe/serious headache, and 
suspected aseptic meningitis) 
The accumulated safety data on 
rozanolixizumab led to an update 
of the adverse events requiring 
special monitoring.  
As of the cut-off date of the IB 
(13 Jul 2022), the following SAEs 
Headache and Meningitis Aseptic 
(PT terms) suggest a possible 
causal relationship to 
rozanolixizumab; based on both 
their temporal association with 
IMP infusion (primarily initial 
infusion) and given the events have 
occurred more than once. There is 
a change in the headache reporting 
process such that severe and/or 
serious headache will be reported 
via the SAE reporting process. 
1.1 Synopsis 
The maximum study duration per 
study participant was updated to 
37 weeks.  
Correction. 
1.3 Schedule of activities, 
Table 1-1 
The visit window for Run-In 
Visit 1 was removed. 
A visit window is not required as 
participants can enter the study 
once their eligibility is confirmed. 
A visit window of ±2d was added 
to Visit 3 
To allow clinical flexibility. 
Footnote b was updated to remove 
reference to the local laboratory. 
The CRO does not have local 
laboratory facilities and therefore 
all tests must be performed at the 
central laboratory. 
Footnote e was updated to include 
Visit 2. 
Added for completeness. 
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Section # and Name 
Description of Change 
Brief Rationale 
Footnote m was added to “Serum 
complement (C3, C4) and plasma 
complement (C3a, C5a).” 
Added for completeness. 
2 Introduction 
Updates to text describing the 
results of completed studies in the 
rozanolixizumab clinical 
development program. 
Update in line with studies status 
at the time of this amendment, and 
to reference the most recent 
information on exposure to 
rozanolixizumab. 
2.3 Benefit/Risk 
Assessment 
Revised text on most common 
adverse drug reactions, potential 
risks, and AESM. 
To update the list of most common 
adverse drug reactions, potential 
risks, and adverse events of special 
monitoring. 
4.4 End of study definition 
The SFU/EOS visit was corrected 
to 5 weeks after the Run-out 
Period. 
Correction.  
5.1 Inclusion criteria 
Inclusion criterion #2 (now #2a) 
was updated to add “or with 
assistance of the caregiver.” 
Inclusion criterion #7 was 
removed.  
To improve clarity and remove 
redundancy across Inclusion 
criteria #2 and #7. 
Inclusion criterion #3 (now #3a) 
was modified.  “Prior confirmed” 
related to fibromyalgia diagnosis 
was removed.  
“Score” was added after “BPI-SF 
interference.” 
The criterion has been updated to 
ensure the study participant meets 
the American College of 
Rheumatology 2016 diagnosis 
criteria at Screening. 
“Score” was added for clarity. 
Inclusion criterion #5 (now #5a) 
was updated to remove male 
contraception requirements. 
To update male contraception 
requirements with current 
guidelines, after completion of the 
required reproductive toxicity 
studies and considering that 
rozanolixizumab has not genotoxic 
potential and potential exposure 
through seminal fluid is expected 
to be negligible. 
5.2 Exclusion criteria 
Exclusion criterion #8 (now #8a) 
was updated to add reference to the 
MDRD study equation for 
assessment of renal impairment. 
To ensure consistency across study 
sites and as requested by the 
agency.  
Exclusion criterion #30 (now #30a) 
was updated to remove “Baseline.”  
Clarification. 
6.5.1 Permitted 
concomitant treatments 
The standard of care medications 
for FMS text was updated. 
To provide clarity and align with 
local prescribing practices. 
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Section # and Name 
Description of Change 
Brief Rationale 
(medications and 
therapies) 
7.1.4 Temporary 
discontinuation of IMP 
Point #1 was updated to remove 
<1.0g/L and add “serum total IgG 
reported below the LLOQ 
(currently 1.09g/L)” 
To accurately reflect the lower 
limit of quantification of the assay 
Point #1 was updated to remove 
<1.0g/L and add “serum total IgG 
reported between the LLOQ 
(currently 1.09g/L)” 
Update of the temporary 
discontinuation in relation to 
COVID-19. 
Update to adapt the withdrawal 
criteria to the evolution of the 
medical practices and local 
guidelines with regards to COVID 
management. 
8.1 Efficacy assessments  
Section 8.1.4 Patient-reported 
outcomes was removed. 
Subsequent subsections were 
renumbered. 
Clarification. 
8.1.1 Brief Pain Inventory-
Short Form 
Paragraph #1 was updated to add 
“including dosing on dosing days.” 
Clarification. 
8.1.5 Fatigue NRS 
Text was added to clarify that the 
Fatigue NRS can be completed by 
the patient at home.  
Clarification. 
8.2.1 Physical examination 
Reference to Visit 1 was updated to 
Visit 0. 
Clarification. 
8.2.2 Neurological 
examination 
Posture was removed. 
During the time of eCRF 
development, posture was not 
available in the data standards, 
however, other variables included 
on the eCRF capture enough 
information. 
8.2.3 Vital signs 
Visit 2 was added to the vital signs 
bulletpoint. 
Updated for consistency to 
schedule of activities. 
8.2.5 Clinical safety 
laboratory assessment 
Reference to local laboratory was 
removed. 
The CRO does not have local 
laboratory facilities and therefore 
all tests must be performed at the 
central laboratory. 
8.2.6.2 Tuberculosis signs 
and symptoms 
questionnaire 
The text regarding the TB 
questionnaire was updated. 
To clarify application of the TB 
questionnaire for the study in 
assessment and management of 
tuberculosis and tuberculosis risk 
factors. 
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Section # and Name 
Description of Change 
Brief Rationale 
8.2.6.3 Tuberculosis 
assessment by IGRA 
References to local laboratory 
IGRA tests were removed.  
The CRO does not have local 
laboratory facilities and therefore 
all tests must be performed at the 
central laboratory. 
8.3.3 Follow-up of AEs 
and SAEs 
“Non-serious” was deleted. 
Clarification. 
8.3.8 Anticipated serious 
adverse events 
Pain was added as an anticipated 
serious adverse event for FMS 
population.  
Other (including FMS-related) 
pain increase and exacerbation of 
FMS can be a serious expected 
event in the FMS population. 
9.1 Definition of analysis 
sets 
The analysis sets and definitions 
were updated. 
Analysis sets updated to match the 
Early Phase SSI accepted standard. 
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint 
The covariate “site” was removed. 
No longer required as site will be 
evaluated in a sensitivity analysis. 
9.7.1 Interim analysis 
A sentence about the timing of the 
interim analysis was added. 
To allow for an earlier interim 
analysis if required. 
10.2 Appendix 2: Clinical 
Laboratory Tests 
Bulletpoint #2 about local 
laboratory results was removed and 
references to dipstick urinalysis and 
local urine testing. 
The CRO does not have local 
laboratory facilities and therefore 
all tests must be performed at the 
central laboratory. 
Blood Urea Nitrogen was updated 
to Urea 
To align with regional 
terminology. 
Glucose (non-fasting) was updated 
to Random Glucose. 
To account for study participants 
who arrive to clinic in a fasted 
state. 
Serology testing for hepatitis A was 
removed. 
To correct an error. 
IGRA TB test and stool samples 
were removed. 
To correct an error as these tests 
are performed by a central 
laboratory. 
Footnote b was removed from the 
IgA, IgE and IgM bulletpoint. 
IgA, IgE, IgM are not blinded 
parameters as the mechanism of 
action of rozanolixizumab does not 
affect these parameters. 
10.4 Appendix 4: 
Contraceptive guidance 
and collection of 
pregnancy information 
Contraception requirements for 
males was removed. 
Follow-up for pregnant partners of 
male study participants was 
removed. 
To update male contraception 
requirements with current 
guidelines, after completion of the 
required reproductive toxicity 
studies and considering that 
rozanolixizumab has not genotoxic 
potential and potential exposure 
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Section # and Name 
Description of Change 
Brief Rationale 
through seminal fluid is expected 
to be negligible. 
10.10 Appendix 10: 
Abbreviations and 
trademarks 
The definitions for CNS, CSF, 
DIAM, MDRD abbreviations were 
added. 
General update. 
10.14 Appendix 14: 
Management of Infections 
and 
Hypoammaglobulinemia 
Paragraph #4 was updated to 
remove <1.0g/L and add “serum 
total IgG reported between the 
LLOQ (currently 1.09g/L).” 
To accurately reflect the 
parameters lower limit of 
quantification of the assay. 
Protocol Amendment 
Summary of Changes 
Table (before the Table of 
Contents) 
Summary of changes and table for 
Protocol Amendment 1 was moved 
to Section 10.11 Appendix 11: 
Protocol amendment history. 
To accommodate the protocol 
amendment summary of changes 
for the most recent amendment 
(#2). 
Global 
Minor administrative, consistency, 
formatting and typographical 
changes have been made 
Updated to provide clarity and be 
consistent with remainder of 
protocol 
 
10.11.2 
Amendment 1 (24 Oct 2022) 
This amendment was 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 reason for this amendment was to incorporate the changes requested by the Medicines and 
Healthcare products Regulatory Agency to the original protocol. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
Paragraph #6 was updated to add 
“internal” before Safety Monitoring 
Committee (SMC). 
To clarify the SMC is a group of 
experts internal to the Sponsor 
which monitors emerging data of 
the study 
1.3 Schedule of activities, 
Table 1-1 
Urine drug screen was added as a 
Screening assessment. A new 
footnote d was added to state that 
urine drug screen for drug abuse 
includes amphetamines, 
barbiturates, benzodiazepines, 
cocaine, cannabinoids, and opiates. 
This test can be performed at other 
visits at the discretion of the 
investigator. Subsequent footnotes 
were renumbered. 
The urine drug screen was added 
as this is a standard procedure at 
the Clinical Research Organization 
(CRO) study sites 
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Section # and Name 
Description of Change 
Brief Rationale 
6.1 Treatments 
administered  
A sentence was added to state the 
approximate duration of study 
treatment sc infusion.  
To clarify the duration and route of 
study treatment administration 
9.7.2 Data monitoring  
Paragraph #1 was updated to add 
“internal” before SMC. A sentence 
was added to state that if required a 
“closed session” may be instituted 
to allow the review of unblinded 
data. Brief details about the closed 
SMC session were added. 
To clarify the SMC is a group of 
experts internal to the Sponsor 
which monitors emerging data of 
the study 
An additional paragraph about the 
Program Independent Data 
Monitoring Committee (PiDMC) 
was added 
To clarify the PiDMC is a group of 
independent experts external to the 
Sponsor assessing progress and 
safety data over the entire 
rozanolixizumab clinical 
development program 
10.1.5 Committees 
structure 
The text was updated to add 
“internal” before SMC. A sentence 
was added to state that if required a 
“closed session” may be instituted 
to allow the review of unblinded 
data. 
To clarify the SMC is a group of 
experts internal to the Sponsor 
which monitors emerging data of 
the study 
An paragraph about the PiDMC 
was added 
To clarify PiDMC is a group of 
independent experts external to the 
Sponsor assessing progress and 
safety data over the entire 
rozanolixizumab clinical 
development program 
10.2 Clinical laboratory 
tests 
Urine drug screen was added 
The urine drug screen was added 
as this is a standard procedure at 
the CRO study sites 
10.10 Abbreviations and 
trademarks 
The definition for the PiDMC 
abbreviation was added 
General update 
 
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10.12 
Appendix 12: Assessment and Management of Tuberculosis 
and Tuberculosis Risk Factors 
Tuberculosis is a safety topic of interest. The safety topics of interest are selected based on 
findings from the IMP clinical program to date, potential risks generally associated with biologic 
immunomodulators, or findings from other medicines with a related mechanism of action. 
For rozanolixizumab clinical studies, the safety topic of interest was selected because it is a 
biologic immunomodulator, although its mechanism of action is less likely to be associated with 
increased risk of infection compared with other immunomodulators such as glucocorticoids. 
10.12.1 
TB definitions 
a. Known TB infection whether present or past is defined as: 
• Active TB disease or clinical signs and symptoms strongly suggestive of TB 
(pulmonary or extrapulmonary). 
• History of active TB disease involving any organ system or findings in other organ 
systems consistent with TB, unless adequately treated and proven to be fully recovered 
upon consultation with an appropriate specialist. 
• Any evidence by radiography or other imaging modalities consistent with previously 
active TB disease that is not reported in the study participant’s medical history. 
b. High risk of acquiring TB infection is defined as: 
• HIV infection. 
• Known close exposure (eg, sleeping in the same room) to another person with active TB 
disease within 3 months prior to Screening. 
• Time spent within 3 months prior to Screening in a healthcare delivery setting or 
institution where individuals infected with TB are housed or where the risk of 
transmission of infection is high. 
c. LTBI is defined as an infection by Mycobacterium tuberculosis with: 
• Evidence of prior exposure (ie, a positive IGRA or TB skin test result) AND 
• Chest imaging (or other imaging) negative for TB infection, AND 
• Absence of signs, symptoms (eg, evidence of organ-specific involvement), or physical 
findings suggestive of TB infection. 
d. Tuberculosis (IGRA) test conversion is defined as a positive or indeterminate (and 
confirmed indeterminate on repeat) IGRA result for the current test when previous IGRA test 
results were negative. 
10.12.2 
Screening Period 
If IGRA TB testing is considered to be performed at Screening, it is recommended that is the 
first study procedure to be performed after signing the ICF. 
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10.12.3 
Physical Examination 
The investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the study participant’s medical or 
social history. The most common primary focus of TB is the lung. Other sites may include 
gastrointestinal system, bone/joints, lymph glands, and meninges, etc. However, in immune 
compromised patients and/or patients treated with biologics, especially TNF inhibitors, extra-
pulmonary manifestations of TB are common compared to a normal population. 
In addition to a physical examination done intermittently throughout the study, study participants 
will be evaluated for medical history and for signs and symptoms of latent or active TB and for 
risk factors for exposure to TB at the following time points: Screening, Baseline, and at regular 
intervals (not less than 12 weeks apart, that is at Week 13 and Week 25) thereafter, including the 
EOT/EW and SFU/EOS. IGRA testing during the study should be performed as clinically 
indicated. 
10.12.4 
Interferon gamma release assay (IGRA) 
IGRA is a whole-blood testing methodology for diagnosing Mycobacterium tuberculosis 
infection. It has become the gold standard but does not allow differentiating LTBI from active 
tuberculosis disease. 
In case an IGRA test is performed in a study participant, the choice of a commercially available 
IGRA test should be made in accordance with current clinical practice. 
The result must be recorded in the eCRF. 
10.12.5 
Practical steps 
In case an IGRA test is required, it will be performed at Screening and the test results will be 
reported as positive, negative, or indeterminate. Schematic representation on IGRA testing is 
presented as follows: 
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Figure 10-1: Decision tree for IGRA TB results at Screening or before entering a 
study 
 
IGRA=interferon-gamma release assay; LTBI=latent tuberculosis infection; TB=tuberculosis 
a IGRA retest must be done during the Screening period. 
b Study participants with LTBI may be randomized in the study only after they have completed at least 1 week of 
appropriate TB preventive therapy and thereafter, will continue and complete the entire preventive therapy. 
If an IGRA is positive or indeterminate, the study participant must be evaluated by an 
appropriate specialist. 
The positive IGRA may represent LTBI or active TB disease. The positive IGRA result may also 
reflect positivity from a prior diagnosed and adequately or inadequately treated past TB 
infection.  
If the IGRA test result is indeterminate, the IGRA previously performed may be repeated once.  
The retest must be done during the Screening Period. If the test is positive or indeterminate on 
Participant
Participant
Participant
Participant
Participant NOT
Participant NOT
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retest, the study participant must not be randomized to IMP without further evaluation by an 
appropriate specialist. 
If upon evaluation by an appropriate specialist, active TB is diagnosed at Screening the study 
participant is not eligible for the study and must not be enrolled. 
If upon evaluation LTBI is diagnosed at Screening, an appropriate TB preventive therapy must 
be initiated and the study participant can be enrolled after successful completion of at least 1 
week of TB preventive therapy. 
Schematic representation on IGRA testing during the study is presented below. 
Figure 10-2: Decision tree for IGRA TB results during a study 
 
ASAP=as soon as possible; IGRA=interferon-gamma release assay; IMP=investigational medicinal product; 
LTBI=latent tuberculosis infection; TB=tuberculosis 
Participant
Participant
Participant
Participant
participant from
participant from
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a IGRA retest must be done ASAP and prior to the next IMP dose 
b Study participants with LTBI may continue the study only after they have completed at least 1 week of appropriate 
TB preventive therapy and thereafter, will continue and complete the entire regimen. 
10.12.6 
IGRA Test Conversion 
All study participants with positive or indeterminate IGRA test results must immediately stop 
IMP administration. In case of a IGRA test conversion, the study participant must be considered 
as having either a suspected new latent or an active TB infection and be promptly referred to an 
appropriate specialist (eg, pulmonologist, infectious disease specialist) for further evaluation. 
Additional assessments (eg, blood tests or IGRA, chest X-rays, or other imaging) should be 
performed where medically relevant and documented. Such conversions should be reported as 
AEs - see Section 10.3. The AE term would need to be updated with final diagnosis once 
available.  
10.12.7 
Latent TB 
In case the evaluation by the appropriate specialist diagnoses a new LTBI, a TB preventive 
therapy in accordance with applicable clinical guidelines should be immediately initiated. The 
investigator must provide full documentation of duration, start and stop dates of TB preventive 
therapy (of at least 1 week duration) and discuss with the UCB study physician (or medical 
monitor) in an anonymized manner prior to allowing study participant to screen (if the LTBI was 
discovered prior to study participant Screening) or prior to receiving IMP (if LTBI was identified 
at Screening) or prior to re-starting the IMP (if LTBI was identified during the study). The 
investigator must assess that the study participant’s likelihood of completing the full course of 
therapy is high and duly record their opinion in the study participant’s record prior to 
randomizing the study participant or re-starting the IMP. 
Evidence of treatment adherence or compliance should be recorded within the treatment 
timeframe and should be completed in appropriate sections of the eCRF. 
If no TB preventive therapy is initiated for the newly diagnosed LTBI, the study participant must 
permanently stop IMP and be withdrawn from the study. Every related action should be 
discussed in advance with the medical monitor. 
Study participants who prematurely discontinue treatment for LTBI or who, in the opinion of the 
investigator or sponsor, are noncompliant with TB preventive therapy must discontinue further 
intake of IMP and be immediately withdrawn. Once withdrawn from study treatment, study 
participants should return for the EOT/EW, complete all EW assessments, and complete an EOS 
Visit. LTBI must be reported as an AE. Follow-up reports should be completed as per protocol 
requirement until such time as the LTBI resolves. 
Additional considerations regarding including LTBI study participants in the study 
• Study participants who initiated treatment for LTBI during the Screening Period should 
repeat chemistry laboratory parameters (can also be done at a local laboratory), medical 
history and all physical examinations for signs and symptoms of TB (after completing at least 
1 week of treatment for LTBI) prior to randomization in the study and must continue the full 
course of TB preventive treatment. 
Rescreening may occur only after discussion with and approval by the study physician (or 
medical monitor). 
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10.12.8 
Active TB 
Study participants who develop active TB during the study must be withdrawn from the study. 
The study participant must be immediately permanently discontinued from study medication and 
an EW Visit must be scheduled as soon as possible, but no later than the next scheduled visit. 
The study participant should be encouraged to keep the EOS Visit as specified by the protocol. 
Treatment for active TB should be started immediately. 
10.12.9 
Safety Reporting Requirements 
The reporting requirements for events relating to TB are as follows: 
• IGRA test conversions defined as a positive or indeterminate (and confirmed indeterminate 
on repeat) should be reported as AEs. The AE term would need to be updated with final 
diagnosis once available. 
• LTBI must be reported as an AE. It is usually reported as a non-serious AE unless it meets 
SAE criteria. Follow-up reports should be completed as per protocol requirement until the 
LTBI resolves. 
• Confirmed active TB is always considered an SAE and must be reported per SAE reporting 
instruction. Follow-up reports should be completed as per protocol requirement until TB 
infection resolves. 
Notes: 
− “TB Positive” is an unclear term and the study investigative site will be queried for 
clarification to obtain event diagnosis. 
− Suspected LTBI and suspected active TB are considered working diagnosis that should 
be clarified before final database lock. The study investigative site will be queried for 
final diagnosis. 
 
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10.13 
Appendix 13: Management of Adverse Event of Special 
Monitoring 
Management of Adverse Event of Special Monitoring 
Adverse events of special monitoring are defined as product specific adverse events, adverse 
reactions, or safety topics requiring special monitoring by one or more regulatory authorities or 
by UCB. For rozanolixizumab, AESMs (defined by UCB) are: 
• Severe and/or serious headache 
• Suspected aseptic meningitis 
Occurrence of AESM require immediate reporting (within 24h of awareness regardless of 
seriousness) to UCB. Upon reception of AESM by UCB a standard medical follow-up query will 
be sent to the site to gather extensive medical information about the AESM. See Table 1-3 for 
assessments that may be required in case of an AESM. 
Suspected Aseptic Meningitis 
Drug-induced aseptic meningitis (DIAM) is a diagnosis of exclusion after ruling out infectious 
causes (Jolles et al, 2000). A few cases of aseptic meningitis (drug-induced) have been reported 
in the rozanolixizumab program. Consequently, suspected aseptic meningitis is being managed 
as an adverse event of special monitoring (see Section 8.3.7). 
Participants should be monitored for signs and symptoms suggestive of central nervous system 
(CNS) involvement and evaluated immediately if meningitis is suspected. A full neurological 
workup should be strongly considered including, but not limited to, imaging, (eg, CT scan, or 
preferably gadolinium enhanced MRI), a lumbar puncture with cerebrospinal fluid (CSF) 
analysis inclusive of glucose, protein, differential complete blood count, cultures, gram stain, 
and/or viral polymerase chain reaction (PCRs), as appropriate. Whenever possible, CSF should 
be stored for assessment of rozanolixizumab PK, PD, specific antibody titers, or other 
biomarkers. A concurrent blood sample should be collected as per local practice. The ultimate 
investigative procedures are at the discretion of the investigator or the treating physician. For 
studies where a neurologist is not the investigator, a neurological consultation is also 
recommended to aid in decision making and patient management. In addition, blood samples for 
exploratory safety biomarkers (see Section 8.9) should be collected for participants with a 
diagnosis of DIAM, preferably within 72 hours after onset of symptoms. These investigations 
will be performed to further understand the potential mechanisms of DIAM in the participants. 
All procedures related to the diagnosis, treatment, and investigation of meningitis should be 
recorded in the eCRF and preliminary data should be included on the SAE form used for 
reporting the event as an AESM within 24 hours (ie, preliminary data reported on the first 
reporting may not have CSF results yet but the reporting should occur as soon as there is a 
suspected diagnosis). Full results should be communicated in subsequent exchanges with the 
sponsor). 
Treatment must be temporarily held if a participant has a diagnosis of suspected meningitis of 
any cause until the diagnostic workup is complete. Based on CSF findings, negative cultures, 
absence of other disease causes, and relationship with IMP a diagnosis of potential DIAM can be 
made (given that the blinded portions of a study should remain blinded to actual treatment 
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assignment). If deemed appropriate by the investigator and agreed upon by the participant and 
the sponsor, the study treatment can resume upon the complete resolution of symptoms. The 
benefit and risk of the treatment should be carefully considered prior to reinitiating the IMP. If a 
participant experiences a second episode of similar symptoms suggestive of DIAM, then the 
participant must discontinue the IMP and treatment must be permanently discontinued. 
Participants experiencing an event of DIAM should be strongly encouraged to remain in the 
study regardless of IMP discontinuation. This will allow for monitoring and follow-up of the 
participant including a complete neurological exam on subsequent physical examinations. 
Longer term follow-up on any AEs related to DIAM that are ongoing may be warranted until 
resolution. Associated symptoms with aseptic meningitis should be managed at the investigator’s 
discretion. 
Severe and/or Serious Headache 
Based on current available clinical data, headache is the most commonly reported adverse drug 
reaction in study participants treated with rozanolixizumab. Study participants should be well 
informed of this potential adverse drug reaction and should be instructed on how to manage it.  
Determination of the severity of headache will be consistent with Common Terminology Criteria 
for Adverse Events (CTCAE) version 5.0 Severe headache is defined as severe pain limiting 
ADL. Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, and 
taking medications.  
In the event of a headache, the investigators should take the medical history of previous 
headaches, concomitant medication, and co-morbidities (eg, asthma) in consideration.  
Severe and/or serious headache is initially reported at a home visit or during a telephone call, the 
study participant should be evaluated by a healthcare professional as soon as possible for further 
investigations. Study participants should be monitored for signs and symptoms suggestive of 
CNS involvement and evaluated immediately if other causes (eg, meningitis, intracranial 
bleeding) are suspected (please see above). In addition, samples for exploratory safety 
biomarkers should be collected for study participants experiencing severe or serious headache 
when possible. These investigations will be performed to further understand the mechanism of 
headaches in the study participants.  
If deemed appropriate by the investigator and agreed upon by the study participant and the 
sponsor, the study treatment can resume treatment upon the resolution of the severe and or 
serious headache event. The benefit and risk of the treatment should be carefully considered 
prior to reinitiating the IMP.  
Headaches will be treated as clinically indicated according to national guidelines. It is 
recommended that the study participants have an analgesic available in case of headache with the 
instruction for frequency and dosage provided by a healthcare professional. The analgesic can be 
started at the early onset of headache. Study participants experiencing any treatment-related 
headache will be followed until resolution of the event. 
Prophylactic treatment of headaches may be permitted for study participants who have 
experienced previous episodes of treatment-related headache after discussion with the medical 
monitor. The benefit risk of continuing treatment with IMP and chronic prophylactic with 
analgesics must be carefully evaluated by the investigator. 
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10.14 
Appendix 14: Management of Infections and 
Hypogammaglobulinemia 
Study participants who have signs or symptoms of any infection should be monitored closely and 
managed according to local guidelines. This may include tests for specific organisms if clinically 
indicated. 
Study participants MUST discontinue IMP, perform the EOT/EW Visit, AND move into the 
SFU Period if the following event occurs: Study participant has a significant infective episode 
including but not limited to bacteremia/sepsis, infectious meningitis, septic arthritis, 
osteomyelitis, complicated pneumonia, or visceral abscess which may or may not result in 
hospitalization. This list is not intended to be all inclusive, and the investigator is expected to 
apply their judgment on continuing IMP based on the clinical situation (Section 7.1.2). 
To maintain the study integrity, IgG level will remain blinded to the study sites and the study 
team (see Section 6.3.1.1 for further details on the maintenance of the study blind). During this 
time, serum IgG level will be monitored by an independent unblinded medical monitor external 
to the study team. As part of the overall safety surveillance, the unblinded medical monitor will 
review available safety information for study participants with low IgG levels and may query the 
site for supportive information. In addition, to preserve the blind, the unblinded medical monitor 
may request additional IgG sampling and/or supportive information for any study participants at 
random. 
The IMP may be temporarily discontinued as requested by the independent unblinded medical 
monitor in case of low serum IgG levels as described in Section 7.1.4. Mock infusions will be 
administered to maintain the blind in case of low IgG levels. 
Treatment may be temporarily discontinued for the study participant who develops a non-serious 
persisting or recurrent infection with a serum total IgG level reported between the LLOQ 
(currently 1.09g/L) and <2g/L. Upon resolution of infection and the IgG returning to the level of 
≥2g/L, the study participant may be allowed to resume treatment with the IMP. Ad hoc 
assessments can be performed to monitor recovery of IgG levels. 
Treatment must be temporarily discontinued for the study participant who develops an event of 
hypogammaglobulinemia with a serum total IgG of <1.09g/L irrespective of infection. When the 
IgG level reaches ≥2g/L, the study participant may be allowed to continue treatment with IMP. 
The risks and benefits of the treatment should be carefully considered prior to reinitiating the 
IMP. 
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10.15 
Appendix 15: Management of Infusion Reactions or 
Hypersensitivity Reactions 
Study participants must be closely monitored for reactions during and after the study drug 
administration period. Standard precautions must be taken for the study participants with regards 
to potential infusion-related reactions. Suggested management guidelines for infusion-related 
reactions or anaphylaxis at the study site are provided in Table 10-4. Definitions of severity of 
the relevant events should be consistent with CTCAE version 5.0. Nurses administering the IMP 
at home should follow their own management guidelines, which should be reviewed and 
endorsed by the investigator prior to first home administration. 
Table 10-4: Suggested management guidelines at site for infusion reactions or 
anaphylaxis 
Type of reaction 
Suggested action 
Acute – Mild 
Grade 1 
Monitor vital signs every 10 min. 
If the reaction worsens to Grade 2, follow the instruction below. 
Acute – Moderate 
Grade 2 
Interrupt/hold infusion temporarily to further assess and initiate 
treatment if necessary. 
Consider the use of iv fluid and antihistamine iv/im. 
Consider administering acetaminophen or NSAIDs. 
Monitor vital signs initially every 5 min. 
If the reaction improves and upon further assessment it is clear that the 
event is not an anaphylaxis, restart the infusion cautiously. Continue to 
monitor vital signs every 5 minutes. 
If reaction recurs or worsens to Grade 3, discontinue infusion. 
Acute – Severe 
Grade 3 or 
anaphylaxis 
Discontinue IMP infusion permanently. 
Alert crash team. 
Maintain airway; ensure oxygen is available. 
Administer: 
− Antihistamine iv/im, corticosteroids iv, epinephrine im, and iv 
fluids as appropriate. 
− Monitor vital signs every 2 min. 
− Hospitalize, if condition not improving or worsens. 
− Monitor patient until symptoms resolve. 
CTCAE=Common Terminology Criteria for Adverse Events; im=intramuscular; IMP=investigational medicinal 
product; iv=intravenous(ly); NSAID=nonsteroidal anti-inflammatory drug 
Note: Management criteria were adapted from the CTCAE v5.0 (National Cancer Institute, 2017). 
Suspected anaphylactic reactions should be diagnosed using Sampson’s Criteria (Sampson et al, 
2006). The infusion must be discontinued immediately and emergency resuscitation measures 
implemented. 
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In study participants experiencing an infusion-related reaction or anaphylaxis, blood samples will 
be collected as soon as possible, while the event is ongoing, to investigate the nature of the 
reaction as per Schedule of Activities (Section 1.3). 
Samples for serum complement (C3, C4) and plasma complement (C3a, C5a) should be 
collected as specified in the Schedule of Activities (Section 1.3). Additional tests such as IgE 
levels, tryptase may be performed when there is a suspicion of Type I or III hypersensitivity 
reaction. The results of all monitoring, including laboratory testing, should be made available to 
the study site and sponsor. 
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11 
REFERENCES 
Chandran A, Schaefer C, Ryan K, et al. The comparative economic burden of mild, moderate, 
and severe fibromyalgia: results from a retrospective chart review and cross-sectional survey of 
working-age U.S. adults. J Manag Care Pharm 2012;18:415–26. 
Cook MK, Malkin M, Karafin MS. The use of plasma exchange in Hashimoto's encephalopathy: 
A case report and review of the literature. J Clin Apher. 2015:30(3):188-192. 
Dyck PJ, Daube J, O'Brien P, et al. Plasma exchange in chronic inflammatory demyelinating 
polyradiculoneuropathy. N Engl. J. Med. 1986;314(8):461-5. 
Goebel A, Krock E, Gentry C, et al. Passive transfer of fibromyalgia symptoms from patients to 
mice. J Clin Invest. 2021;131(13):e144201. 
Guptill JT, Juel VC, Massey JM, et al. Effect of therapeutic plasma exchange on 
immunoglobulins in myasthenia gravis. Autoimmunity. 2016:49(7):472-9. 
Häuser W, Ablin J, Fitzcharles MA, et al. Fibromyalgia. Nat Rev Dis Primers. 2015;1:15022. 
doi: 10.1038/nrdp.2015.22. PMID: 27189527. 
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, Sewell WAC, Leighton C. Drug-induced aseptic meningitis: diagnosis and 
management. Drug Saf. 2000:22(3): 215-26. 
Kaplan AA. Therapeutic plasma exchange: a technical and operational review. J Clin Apheres. 
2013;28(1):3-10. 
Krock E, Morado-Urbina CE, Menezes J, et al. Fibromyalgia patients with elevated levels of 
anti-satellite glia cell immunoglobulin G antibodies present with more severe symptoms. Pain. 
2023 ; Online ahead of print. 
Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the 
management of fibromyalgia. Annals of the rheumatic diseases. 2017;76(2):318-28. 
Mascarenhas RO, Souza MB, Oliveira MX, et al. Association of Therapies With Reduced Pain 
and Improved Quality of Life in Patients With Fibromyalgia: A Systematic Review and Meta-
analysis. JAMA Intern Med. 2021;181(1):104-112. 
Mease PJ, Spaeth M, Clauw DJ, et al. Estimation of minimum clinically important difference for 
pain in fibromyalgia. Arthritis Care Res (Hoboken). 2011;63(6):821-6. 
Peter HH, Ochs HD, Cunningham-Rundles C, Vinh DC, Kiessling P, Greve B, Jolles S. 
Targeting FcRn for immunomodulation: Benefits, risks, and practical considerations. J Allergy 
Clin Immunol. 2020 Sep;146(3):479-491 
Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 
2007;7(9):715-25. 
Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and 
management of anaphylaxis: summary report – Second National Institute of Allergy and 
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Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 
2006;117(2):391-7. 
Turner MS, Sutton D, Sauder DN. The use of plasmapheresis and immunosuppression in the 
treatment of pemphigus vulgaris. J Am Acad Dermatol. 2000;43(6):1058-64. 
Vyvgart Prescribing Information, 2021. https://www.argenx.com/product/vyvgart-prescribing-
information.pdf. 
White LA, Birnbaum HG, Kaltenboeck A, et al. Employees with fibromyalgia: medical 
comorbidity, healthcare costs, and work loss. J Occup Environ Med 2008;50(1):13–24. 
Williams DA, Arnold LM. Measures applied to the assessment of fibromyalgia: Fibromyalgia 
impact questionnaire (FIQ), brief pain inventory (BPI), the multidimensional fatigue inventory 
(MFI-20), the MOS sleep scale, and the multiple ability self-report questionnaire (MASQ; 
cognitive dysfunction). Arthritis Care Res (Hoboken). 2011; 63(0 11): S86–S97. 
doi:10.1002/acr.20531. 
Williams ME, Balogun RA. Principles of separation: indications and therapeutic targets for 
plasma exchange. Clin J Am Soc Nephrol. 2014;9(1):181-90. 
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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:
fm0001-protocol-amend-3-14Apr2023
Version:
1. 0
Document Number:
CLIN-000214789
Title:
fm0001-protocol-amend-3-14Apr2023
Approved Date:
14 Apr 2023
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 14-Apr-2023 10:07:40 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 14-Apr-2023 11:15:35 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Medical
Date of Signature: 14-Apr-2023 11:45:11 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 14-Apr-2023 13:27:29 GMT+0000
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SAP_001.pdf: 
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Statistical Analysis Plan v2.0 
Rozanolixizumab 
FM0001 
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STATISTICAL ANALYSIS PLAN 
Study: FM0001 
Product: Rozanolixizumab 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PHASE 2A, PROOF-OF-CONCEPT STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF 
ROZANOLIXIZUMAB TO TREAT ADULT STUDY 
PARTICIPANTS WITH SEVERE FIBROMYALGIA SYNDROME 
SHORT TITLE: 
A Phase 2A proof-of-concept study to evaluate the efficacy and safety of rozanolixizumab to 
treat adult study participants with severe fibromyalgia syndrome 
Sponsor Name: UCB Biopharma SRL 
Legal Registered Address: Allée de la Recherche 60, 1070 Brussels BELGIUM 
Regulatory Agency Identifier Number(s): 
Registry 
ID 
EudraCT Number: 
2022-001523-32 
IND Number: 
Not applicable 
NCT Number: 
Currently not available 
Confidentiality Statement 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... 5 
1 
INTRODUCTION ............................................................................................................. 8 
1.1 
Objectives and Endpoints .............................................................................................. 8 
1.2 
Study Design ................................................................................................................ 10 
2 
STATISTICAL HYPOTHESES ...................................................................................... 12 
3 
SAMPLE SIZE DETERMINATION .............................................................................. 12 
4 
POPULATIONS FOR ANALYSIS ................................................................................. 12 
5 
STATISTICAL ANALYSES .......................................................................................... 14 
5.1 
General Considerations ................................................................................................ 14 
5.1.1 
General Study Level Definitions ......................................................................... 15 
5.1.1.1 
Study and Period Day ................................................................................ 15 
5.1.1.2 
Study Periods ............................................................................................. 15 
5.1.1.3 
Definition of Baseline Values ................................................................... 16 
5.1.1.4 
Treatment Assignment and Treatment Group ........................................... 18 
5.1.2 
Changes to Protocol-Defined Analyses ............................................................... 18 
5.1.3 
Protocol Deviations ............................................................................................. 19 
5.1.3.1 
COVID-19 Related Protocol Deviations ................................................... 19 
5.1.4 
Handling of Dropouts or Missing Data ............................................................... 20 
5.1.5 
Handling Repeated and Unscheduled Measurements .......................................... 20 
5.1.6 
Center Pooling Strategy ....................................................................................... 21 
5.1.7 
Coding Dictionaries ............................................................................................. 21 
5.2 
Study Population Characteristics ................................................................................. 21 
5.2.1 
Participant Disposition ......................................................................................... 21 
5.2.2 
Impact of COVID-19 on Study Visits ................................................................. 22 
5.3 
Demographics and Other Baseline Characteristics ...................................................... 22 
5.3.1 
Demographics ...................................................................................................... 22 
5.3.2 
Other Baseline Characteristics ............................................................................. 23 
5.3.3 
Medical History ................................................................................................... 23 
5.3.4 
History of Headache ............................................................................................ 23 
5.3.5 
Medical History on Pain Management Programs ................................................ 23 
5.3.6 
Prior and Concomitant Medications .................................................................... 23 
5.3.7 
Prior and Concomitant Medical Procedures ........................................................ 24 
5.4 
Measurements of Treatment Compliance .................................................................... 24 
5.5 
Pharmacokinetics and Pharmacodynamics .................................................................. 25 
5.5.1 
Pharmacokinetics ................................................................................................. 25 
5.5.2 
Pharmacodynamics .............................................................................................. 25 
5.6 
Safety Analysis ............................................................................................................ 26 
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5.6.1 
Extent of Exposure .............................................................................................. 26 
5.6.2 
Adverse Events .................................................................................................... 27 
5.6.3 
COVID-19 AEs ................................................................................................... 30 
5.6.4 
AEs of Special Interest and AEs of Special Monitoring ..................................... 30 
5.6.5 
Adverse Events of Focus (AEOF) ....................................................................... 30 
5.6.6 
Clinical Laboratory Evaluations .......................................................................... 31 
5.6.7 
Vital Signs ........................................................................................................... 32 
5.6.8 
Electrocardiograms (ECG) .................................................................................. 32 
5.6.9 
Other Safety Variable(s) ...................................................................................... 33 
5.6.9.1 
Physical examination ................................................................................. 33 
5.6.9.2 
Neurological Examination ......................................................................... 33 
5.6.9.3 
Suicidal Risk Monitoring - C-SSRS .......................................................... 33 
5.6.9.4 
Assessment of Tuberculosis and Tuberculosis Risk Factors ..................... 33 
5.6.9.5 
Potential Drug-Induced Liver Injury (pDILI) ........................................... 34 
5.7 
Immunogenicity ........................................................................................................... 35 
5.8 
Efficacy Analysis ......................................................................................................... 42 
5.8.1 
Derivations of Efficacy Variables(s) ................................................................... 43 
5.8.2 
Primary Efficacy Variable ................................................................................... 44 
5.8.2.1 
Primary Analysis of Primary Efficacy Variables(s) .................................. 44 
5.8.2.2 
Secondary Analysis of Primary Efficacy Variable(s) ............................... 45 
5.8.3 
Supportive and Sensitivity Analyses of the Primary Efficacy Variable .............. 46 
5.8.4 
Derivations of Secondary and Exploratory Efficacy Variables ........................... 46 
5.9 
Other Analyses ............................................................................................................. 47 
5.9.1 
Pressure Pain Threshold ...................................................................................... 47 
5.10 
Biomarkers ................................................................................................................... 47 
5.11 
Immunological Endpoint ............................................................................................. 47 
5.12 
Early readout analysis and data monitoring ................................................................. 48 
5.12.1 
Early Readout Analysis ....................................................................................... 48 
5.12.2 
Data Monitoring ................................................................................................... 48 
6 
CTR AND DSUR OUTPUTS ......................................................................................... 48 
6.1 
CTR .............................................................................................................................. 48 
6.2 
DSUR ........................................................................................................................... 49 
7 
REFERENCES ................................................................................................................ 50 
8 
APPENDICES ................................................................................................................. 51 
8.1 
Appendix 1: Abnormality Criteria for Laboratory and Vital Sign Parameters ............ 51 
8.1.1 
Laboratory Assessments Marked Abnormality Criteria ...................................... 51 
8.1.2 
Vital signs ............................................................................................................ 52 
8.2 
Appendix 2: Handling of Dates ................................................................................... 53 
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8.2.1 
Adverse Events .................................................................................................... 53 
8.2.2 
Medications .......................................................................................................... 55 
8.2.3 
Procedures ............................................................................................................ 56 
8.2.4 
Time Since Diagnosis / First Symptoms of FMS ................................................ 56 
8.3 
Appendix 3: AEOF ...................................................................................................... 57 
8.4 
Appendix 4: Period of Onset Assignment ................................................................... 58 
8.4.1 
Adverse Events and IPDs .................................................................................... 58 
8.4.2 
Medications .......................................................................................................... 59 
9 
AMENDMENT(S) TO THE STATISTICIAL ANALYSIS PLAN (SAP) ..................... 60 
9.1 
Amendment 1 ............................................................................................................... 60 
 
LIST OF TABLES 
Table 1-1: 
Objectives and Estimands/Endpoints ................................................................. 8 
Table 5-1:  
Study days and periods .................................................................................... 15 
Table 5-2: 
Definition of Baseline ...................................................................................... 17 
Table 5-3: 
Treatment Group Descriptions ......................................................................... 18 
Table 5-4: 
Sequence Descriptions ..................................................................................... 18 
Table 5-5: 
Period descriptions ........................................................................................... 18 
Table 5-6:  
ADA Sample Status ......................................................................................... 35 
Table 5-7:  
ADA Participant Status Categories .................................................................. 37 
Table 5-8:  
Efficacy endpoint time points .......................................................................... 43 
 
 
 
 
 
 
 
 
 
 
 
 
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   LIST OF ABBREVIATIONS 
  
ADA 
antidrug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
AESM 
adverse event of special monitoring 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ALQ 
above the limit of quantification 
AST 
aspartate aminotransferase 
ASP 
All Study Participants Set 
BLQ 
below the limit of quantification 
BMI 
body mass index 
BPI-SF 
Brief Pain Inventory-Short Form 
CI 
confidence interval 
CRO 
contract research organization 
CSR 
clinical study report 
C-SSRS 
Columbia Suicidality Severity Rating Scale 
CV 
coefficient of variation 
DEM 
Data Evaluation Meeting 
DILI 
drug-induced liver injury 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
eCRF 
Electronic Case Report Form 
EDV 
Early Discontinuation Visit 
EMA 
European Medicines Agency 
ePRO 
electronic patient reported outcome 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FIQR 
Revised Fibromyalgia Impact Questionnaire 
FMS 
Fibromyalgia syndrome 
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geoCV 
Geometric coefficient of variation 
geoMean 
Geometric mean 
ICF 
Informed Consent Form 
ICH 
International Council For Harmonisation 
Ig 
immunoglobulin 
IGRA 
Interferon-Gamma Release Assay 
IMP 
Investigational Medicinal Product 
IPD 
important protocol deviation 
LLOQ 
lower limit of quantification 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
NAb 
Neutralizing antibody 
NI 
Negative immunodepletion 
NRS 
Numeric rating scale 
NS 
Negative Screen 
PD 
Pharmacodynamic 
pDILI 
Potential drug-induced liver injury  
PDS 
Pharmacodynamic Set 
PI 
Positive immunodepletion 
PK 
Pharmacokinetic 
PKS 
Pharmacokinetic Set 
PS 
Positive Screen 
PT 
Preferred Term 
PBO 
Placebo 
RLZ 
Rozanolixizumab 
RS 
Randomized Set 
QTcF 
QT interval corrected using Fridericia’s formula 
QW 
Once Weekly 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
sc 
Subcutaneous 
SD 
Standard Deviation 
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SOC 
System Organ Class 
SFU 
Safety follow-up 
SMC 
Safety monitoring committee 
SS 
Safety Set 
SS-r 
Safety Set - as randomized  
SS-t 
Safety Set - as treated  
SSD 
Safety signal detection 
TB 
Tuberculosis 
TFL 
tables, figures and listings 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
WHO-DD 
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 FM0001. The SAP summarizes what will be 
provided in the tables, figures and listings (TFLs) to be included in the final clinical study report 
(CSR) according to the protocol, as well as defining the output to be generated for safety signal 
detection (SSD) and for the Early Readout Analysis. The TFL specifications are contained in a 
separate document and are based on the UCB Standard TFL Shells. The requirements for the 
Early Readout Analysis will be defined in the Unbinding Plan and the Safety Monitoring 
Committee (SMC) procedures will be defined in a separate charter.  
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 amended accordingly. In addition, if the 
methodology for the analysis of primary or secondary endpoints must be modified or updated 
prior to unblinding, a SAP amendment will be required. If, after unblinding, additional analyses 
are required to supplement the planned analyses described in this SAP, these changes will be 
described in the CSR together with the associated rationale. Other minor changes to non-key 
analyses will also be documented in the CSR. 
The content of this SAP is compatible with the International Council for Harmonisation 
(ICH)/Food and Drug Administration (FDA) E9 Guidance documents (Phillips et al, 2003).  
1.1 
Objectives and Endpoints 
Objectives, endpoints and applicable estimands are described in Table 1-1 below.  
Table 1-1: Objectives and Estimands/Endpoints 
Objectives 
Endpoints/Estimands 
Primary 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
Primary estimand (efficacy): 
• Treatment: rozanolixizumab 560 mg QW 
or Placebo QW 
• Target Population: study participants with 
severe FMS 
• Endpoint: BPI-SF average interference 
score after 12 weeks of double-blind 
treatment. 
• Intercurrent event handling: 
− The ICE discontinuation of treatment 
will be handled using a hypothetical 
strategy assuming that the study 
participants did not experience the 
events, with data following 
discontinuation excluded from 
analysis. 
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Table 1-1: Objectives and Estimands/Endpoints 
Objectives 
Endpoints/Estimands 
• Population level summary: mean 
difference in average BPI-SF interference 
score between the two treatments 
Secondary 
• To assess the safety and tolerability of 
rozanolixizumab in study participants 
with severe FMS 
• Occurrence of TEAEs during the study 
• TEAEs leading to withdrawal of IMP 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
• BPI-SF average interference score after 24 
weeks of treatment 
• FIQR score after 10 weeks of treatment 
• Mean 7-day average daily pain score 
(Pain NRS) after 12 weeks of treatment 
• Mean 7-day fatigue score (Fatigue NRS) 
after 12 weeks of treatment 
Exploratory 
• To assess the PK of rozanolixizumab in 
study participants with severe FMS 
• Plasma concentration of rozanolixizumab 
prior to dosing on Week 13 and Week 25 
• To evaluate the efficacy of 
rozanolixizumab for treatment of study 
participants with severe FMS 
• Pressure pain threshold as measured by 
pressure algesiometry 
• To assess the safety and tolerability of 
rozanolixizumab in study participants 
with severe FMS 
• Change from Baseline in vital signs and 
laboratory results at scheduled 
assessments during the Treatment Period 
through the Run-Out Period 
• To evaluate the incidence and emergence 
of ADA of rozanolixizumab in study 
participants with severe FMS 
• Antidrug antibody incidence at scheduled 
assessments during the Treatment Period 
• To assess the PD effect of 
rozanolixizumab in study participants 
with severe FMS 
• Value (absolute) and change from 
Baseline (absolute and percentage) in 
serum total IgG and IgG subclasses at 
scheduled assessments during the 
Treatment Period 
• To assess the effect of rozanolixizumab 
on exploratory biomarkers in study 
participants with severe FMS 
• Assessment of IgG binding in in vitro cell 
assay at scheduled assessments during the 
Treatment Period and the Run-Out Period 
• Assess genetic variation for potential 
effects on disease progression and/or drug 
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Table 1-1: Objectives and Estimands/Endpoints 
Objectives 
Endpoints/Estimands 
response and also any changes in 
epigenetics 
• Exploratory biomarkers may be measured 
to evaluate changes from Baseline in 
response to rozanolixizumab 
1.2 
Study Design 
This is a Phase 2A, multi-center, randomized, double-blind, placebo-controlled, proof-of-concept 
study to evaluate the efficacy, safety, PK, and PD of rozanolixizumab for the treatment of severe 
FMS. Study participants who have a confirmed diagnosis of FMS and have been diagnosed for at 
least 6 months, with symptoms for at least 2 years before enrollment will be considered for the 
study.  
Study participants enrolled under Protocol Amendments 1 and 2, must meet the following 
criteria during the Screening Period: 
− BPI-SF interference score ≥6 
− FIQR score ≥64 
− Fatigue NRS score ≥5 
− Completed a pain management program of at least 36 hours duration, completion must 
have been >6 months from study entry date  
− Mean daily average 24h pain intensity ≥5 and <10 assessed by Pain NRS for at least 7 of 
the last 10 consecutive days of the Screening Period. 
− Pain NRS scores ≥4 at all completed assessments in the last 10 consecutive days of the 
Screening Period. 
Study participants enrolled under Protocol Amendment 3 must meet the following criteria during 
the Screening Period: 
− BPI-SF interference score ≥6 
− Mean daily average 24 hours pain intensity ≥6 and <10 assessed by Pain NRS. This will 
be assessed over a 10-day period within the Screening Period. Study participants require 
a minimum of 7 out of 10 assessments over the 10-day period. 
− Pain NRS scores ≥4 at all completed assessments within the 10-day period. 
In total and allowing for a dropout rate of 25%, approximately 60 study participants are planned 
to be enrolled and randomized in the study at up to 8 centers from the UK, with a target of 
48 study participants completing the study.  
The study will consist of a Screening Period of up to 28 days, a 2-week, single-blind Run-In 
Period, 2 subsequent 12-week, double-blind Treatment Periods, followed by a 2-week, single-
blind Run-Out Period and a 5-week SFU Period. 
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Study participants will be randomized in a 1:1:1 ratio to 1 of 3 sequences. The study participants 
in each sequence will receive the following treatment regimen during the double-blind Treatment 
Periods (see Figure 1-1): 
• Sequence 1: Rozanolixizumab 560 mg sc QW for 24 weeks (12 + 12 weeks Treatment 
Period) (N=20, Group 1) 
• Sequence 2: Placebo sc QW for 12 weeks, followed by rozanolixizumab 560 mg sc QW for 
12 weeks (N=20, Group 2) 
• Sequence 3: Placebo sc QW for 24 weeks (N=20, Group 3). 
Figure 1-1: Study Schematic 
 
EOS=end of study; QW=once weekly; sc=subcutaneous. 
Note: All study participants receive placebo in a single-blind manner during the Run-In and Run-Out Periods. 
The two 12-week period design allows for both intra- and inter-study participant comparisons. 
Sequence 2 allows for intra-study participant comparison of 12 weeks receiving placebo and 
12 weeks receiving rozanolixizumab. Sequence 3, which has placebo throughout, enables 
adjustments for any period effects, and Sequence 1 Treatment Period 1 allows for inter-study 
participant comparisons with both Sequence 2 (Treatment Period 1) and Sequence 3 (Treatment 
Period 1 and Treatment Period 2). 
In addition, comparing treatment effects after 24 weeks of treatment is possible through comparing 
the 24-week assessments from Sequence 1 and Sequence 3. 
The initial 2-week Run-In Period and the final 2-week Run-Out Period will be study participant-
blind, with study participants not informed that they are receiving placebo, to limit the impact of 
any start-of-study or end-of-study induced placebo effects. The two 12-week treatment periods 
will be study participant-, investigator-, and sponsor-blind. It is important that study participants 
do not know when their treatment changes, whether it is going from Run-In to Treatment Period 1, 
Treatment Period 1 to Treatment Period 2, or Treatment Period 2 to Run-Out. 
The endpoint-specific Baseline definitions are summarized in Section 5.1.1.  
For study participants enrolled under Protocol Amendments 1 and 2, the mean average daily pain 
over the previous 24 hours will be captured by the Pain NRS through a diary for at least 7 of the 
last 10 consecutive days of the Screening Period.  
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For study participants enrolled under Protocol Amendment 3, the daily average pain over the 
previous 24 hours will be captured using the Pain NRS through a diary over a 10-day period within 
the Screening Period. Study participants require a minimum of 7 out of the 10 daily Pain NRS 
assessments over this 10-day period to be eligible for randomization. 
All recorded Pain NRS scores over the 10-day period within the Screening Period will be used to 
calculate the mean daily average 24 hours pain intensity score (for example, if 10 daily scores are 
available take the mean of the 10 days; if 9 daily scores are available take the mean of the 9 days 
and so on). 
During the Run-In Period and at the end of the Treatment Periods, the Pain NRS will be collected 
at the assessment visit and for the 6 consecutive days following the visit, as described in the 
protocol. For all other visits, the average pain for the preceding 24 hours prior to the visit will be 
captured by the Pain NRS for that day only.  
2 
STATISTICAL HYPOTHESES 
No formal statistical hypothesis testing is planned in this study. 
3 
SAMPLE SIZE DETERMINATION 
The operating characteristics of the design were evaluated using a simulation approach and based 
on estimates of variability and treatment effects from fibromyalgia studies reported in 
clinicaltrials.gov and other papers. BPI-SF was used consistently in duloxetine studies. A sample 
size of 48 completed study participants gives more than 80% probability that if the true 
difference of the mean BPI-SF interference score after 12 weeks of treatment on 
rozanolixizumab compared with placebo was 1.0 units or better, then the comparison would pass 
a 1-sided 10% significance test. This assumes a between-study participant standard deviation 
component for the BPI-SF interference score of 1.74 units, and a within-study participant SD of 
1.5 units (a total between-study participant SD of 2.3 units) after accounting for the Baseline 
BPI-SF interference score. Through simulations of the design, it was estimated that 60 study 
participants starting the study would achieve the desired power, assuming a drop-out rate of 
25%, and assuming a uniform distribution of drop-out timings. This accounts for the fact that 
drop-out participants contribute partial information up to the point of discontinuation and 
corresponds to an effective sample size of 48. 
Simulations including the interim analysis were also conducted, and based on the impact on the 
operating characteristics, it was decided that no multiplicity adjustment was needed for the final 
analysis.  
4 
POPULATIONS FOR ANALYSIS 
All Study Participants Set:  
The All Study Participants Set (ASP) consists of all study participants that sign the informed 
consent form. This set includes screening failures.  
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Randomized Set: 
The Randomized Set (RS) will consist of all participants randomized into the study.    
Safety Set –as Randomized:  
The Safety Set as randomized (SS-r) consists of all study participants who received any study 
treatment, including during the Run-In period. The study participants will be analyzed according 
to the randomized treatment groups during the specific treatment period.  
The SS-r will be used for production of safety analysis by visit and demographic and 
immunogenicity analysis.  
Safety Set – as Treated:  
The Safety Set as treated (SS-t) consists of all study participants who received any study 
treatment, including during the Run-In period. 
For analysis purposes, the SS-t is used only for tabulating AEs, as described in 
Section 5.6.25.6.2.  
Full Analysis Set:  
The Full Analysis Set (FAS) consists of all study participants in the SS-r who have a Baseline 
value and at least one post-Baseline efficacy endpoint assessment. Study participants who 
receive at least one dose of treatment not per randomization schedule will be excluded from the 
FAS. 
This analysis set will be used for the summaries and analyses of primary, secondary, and 
exploratory efficacy variables data.  
Pharmacokinetic Set:  
The Pharmacokinetics Set (PKS) consists of all study participants in the SS-r who have at least 
one dose of active IMP and at least one measurable PK concentration, including below limit of 
quantification (BLQ) samples. The PKS will be used for all PK summaries and analyses. If a 
study participant in the PKS is missing individual time points or are otherwise unobservable, 
they will be included in the PKS but those time points will be omitted from the PK summaries, 
as appropriate.  
Pharmacodynamic Set:  
Pharmacodynamic set (PDS) is a subset of the FAS, 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 unblinding), and who had at least one valid post-Baseline 
measurement of serum total IgG or IgG subclasses. The final PDS will be identified after 
unblinding to confirm availability of at least one post-baseline valid measurement due to 
blinding. PDS will be used for all PD summaries and analyses. 
Participants who had important protocol deviations affecting the relevant efficacy/PK/PD 
variables, as confirmed during a pre-analysis review of the data prior to unblinding may be 
excluded from relevant analyses. Such exclusions will be agreed and documented prior to 
unblinding and will be described in TFLs and/or the CSR.  
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5 
STATISTICAL ANALYSES 
5.1 
General Considerations  
All tables, figures, and listings (TFLs), including statistical evaluation, will be produced by 
Veramed using SAS version 9.4 or higher (SAS Institute, Cary, North Carolina, USA). Analysis 
data will adhere to Clinical Data Interchange Standards Consortium (CDISC) guidance 
documents for Analysis Data Model (ADaM) and follow the UCB interpretation.  
Listings will be presented by study participant and planned treatment sequence. The presentation 
of tables and figures varies from variable to variable and will be specified in the respective 
section. 
All tabulations will be performed per specified analysis set, visit and time point (where 
applicable). Details of planned tabulations will be described in the TFL shells. Data listings 
containing all documented data and all derived data will be generated. 
1) Categorical Variables  
Categorical variables will be summarized using frequency counts and percentages. Unless 
otherwise stated, the denominator for the percentage calculations will be based on the number of 
study participants in the respective analysis set, treatment sequence, treatment group, visit and 
time point (as applicable) with non-missing data. If there are any study participants with missing 
values for a categorical variable, an additional row displaying the number of study participants 
with missing data will be added.  
2) Continuous Variables 
Summary statistics will be presented for continuous variables including number of participants 
(n), mean, standard deviation (SD), median, minimum and maximum. Geometric mean 
(geoMean), geometric coefficient of variation (geoCV) and 95% CI for the geoMean will also be 
presented in the summaries of PK concentration data. The 25th and 75th percentiles (Q1 and Q3) 
will be included for descriptive statistics of ePRO data.  
When reporting descriptive statistics, the following rules will apply: 
• Mean (arithmetic and geometric), SD, Q1, Q3, and median will use 1 decimal place more, or 
1 significant figure more than the original data 
• Confidence intervals will use 1 decimal place more, or 1 significant figure more – depending 
on the reporting format of the original data – than the value around which the confidence 
interval is constructed 
• Coefficient of variation (CV) will be reported as a percentage to 1 decimal place 
• Minimum and maximum will be reported using the same number of decimal places or 
significant figures as the original value 
• If no participants have data at a given time point, then only n=0 will be presented. If n<3, 
then only the n, minimum and maximum will be presented. If n=3, then only n, minimum, 
mean, median and maximum will be presented. The other descriptive statistics will be left 
blank. 
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5.1.1 
General Study Level Definitions 
5.1.1.1 
Study and Period Day 
Study day for an event or measurement occurring before the date of the first dose of Treatment 
Period 1 will be calculated as follows:  
Study Day=Event/Measurement Date−Date of First Dose 
Study day for an event or measurement occurring on the date of the first dose of Treatment 
Period 1 is 1. Study day for an event or measurement occurring on or after the date of the first 
dose to the date of the last dose including Run-Out period will be calculated as follows:  
Study Day = (Event/Measurement Date−Date of First Dose) + 1  
For events or measurements occurring after the date of the last dose including Run-Out period 
study day will be prefixed with ‘+’ in the data listings and will be calculated as follows: 
Study Day = + (Event/Measurement Date−Date of Last Dose of the study) 
 Period day for an event or measurement occurring on the date of the first dose in a Treatment 
Period is 1. Period day for an event or measurement occurring on or after the date of the first 
dose to the day before the date of the first dose in the following Treatment Period will be 
calculated as follows:  
Period Day = (Event/Measurement Date−Date of First Dose in a Treatment Period) + 1  
There is no Study Day 0. For the purpose of the study participant data listings, study day or 
period day will not be calculated if the event/measurement date is partial. Instead, study day or 
period day will be presented as ‘--‘in the relevant participant data listing. Table 5-1 below 
describe the ranges of study and period days during the study.  
Table 5-1:  Study days and periods  
 
Screening & 
Run-In  
Treatment 
Period 1  
Treatment 
Period 2 
Run-Out 
Period 
Safety FU 
Period 
 
Day-42 to Day 
-1 
Day 1 to Day 84  Day 85 to 
Day 168 
Day 169 to 
Day 182 
Day 183 to 
Day 218 
Study Day 
-42 to -1 
1 to 84 
85-168 
169-182 
+1 to +35 
Period Day 
 
1 to 84 
1 to 84 
  
  
5.1.1.2 
Study Periods 
The maximum study duration per study participant will be 37 weeks. 
• Screening Period (Day -42 to Day -15): Eligibility will be assessed during the Screening 
Period of up to 28 days 
• Run-In Period (Day -14 to Day -1): Study participants who have been confirmed eligible to 
participate in the study will be randomized 1:1:1 to study treatment. During the 2-week Run-
In Period, all study participants will receive placebo sc QW and will be blinded to this 
treatment. 
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• Treatment Period 1 (Day 1 to Day 84): Study participants will receive their randomized 
treatments for the first 12-week Treatment Period. 
• Treatment Period 2 (Day 85 to Day 168): Study participants will receive their randomized 
treatments for the second 12-week Treatment Period. 
• Run-Out Period (Day 169 to Day 182): At the end of both 12-week Treatment Periods, all 
study participants will receive placebo sc QW during a 2-week Run-Out Period and will be 
blinded to this treatment. 
• Safety Follow-up Period (SFU, Day 183 to Day 218): Study participants who complete both 
Treatment Periods and Run-Out Period will enter the 5-week SFU Period.  
• Study participants who permanently discontinue IMP are encouraged to complete the 
EOT/EW Visit and the SFU/End of Study (EOS) Visit. In these cases, the SFU will not take 
place between study Day 183 to Day 218.  
• Safety analysis will include periods from Run-In through end of SFU period. Efficacy, PK 
and PD analysis will include data collected from Treatment Period 1 to end of SFU Period.  
Efficacy, PK and PD measurements collected post-Baseline and up to and including Visit 15 will 
be allocated to Treatment Period 1. Efficacy, PK and PD measurements collected after Visit 15 
and up to and including Visit 27 will be allocated to Treatment Period 2.  
For the purposes of analysis, data including AEs, IPDs, and medications will be assigned a study 
period using the rules summarized in Appendix 4 Section 8.4.  
 
5.1.1.3 
Definition of Baseline Values  
Endpoint-specific Baseline definitions are presented in Table 5-2. Scheduled or unscheduled 
measurements may be used as the Baseline value. If a measurement is missing or repeated at 
Baseline, and is obtained prior to the first dose of IMP in the Run-In Period/at Day 1 (dependent 
upon the endpoint), then the last available measurement will be used as the Baseline value. In 
rare circumstances the latest observation may be a data point collected at an unscheduled visit - 
such an observation would also be allowable as Baseline value.  
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Table 5-2: 
Definition of Baseline 
Endpoint 
Definition of Baseline 
Hematology, serum 
chemistry, urinalysis, vital 
signs 
Baseline is defined as the most recent value obtained prior to the first 
dose of IMP in the Run-In Period, or Screening if this is missing. 
 
Efficacy  
Baseline is defined as the measurements on Day 1 (Visit 3, Week 1) 
prior to administration of treatment or during Run-In Period depending 
on the endpoint:  
• 
For BPI-SF, the Baseline measurement is at Day 1 (Visit 3, Week 
1). If Day 1 measurement is missing, then the Screening 
measurement will be used.  
• 
For Pain NRS, and Fatigue NRS, the Baseline measurement will 
be the average of the 7 days prior to Day 1 (Visit 3, Week 1), not 
including Day 1 data. If there are <3 assessments available within 
the 7 days, the Baseline measurement will be missing.  
• 
For FIQR, the Baseline will be the last assessment before Day 1. 
This is Day -7 (Visit 2, Week -1) or Screening visit if Day-7 is 
missing.  
Note that for all endpoints listed above, if a dose of study medication 
was not received at Visit 3, but the efficacy assessment was performed 
at Visit 3 (or Visit 2 for FIQR), the Baseline assessment would be 
defined as above.  
Pharmacodynamics (PD) 
Baseline is defined as the latest non-missing assessment performed 
prior to dosing on Day 1 (Visit 3, Week 1). If Day 1 measurement is 
missing, the Run-In (Visit 1, Week -2) measurement will be used.  
Note that if a dose of study medication was not received at Visit 3, but 
the PD assessment was performed at Visit 3, this would still be used as 
the Baseline assessment. 
Pressure Pain Threshold 
Baseline is defined as the average of the three assessments performed 
per site, prior to dosing on Day 1 (Visit 3, Week 1). 
Note that if a dose of study medication was not received at Visit 3, but 
the Pressure Pain Threshold assessment was performed at Visit 3, this 
assessment would still be used as the Baseline assessment. 
Anti-drug antibody (ADA) 
Baseline is defined as the last measurement prior to receiving the first 
dose of rozanolixizumab. For participants randomized to Sequence 1, 
Baseline is the Day 1 (Visit 3, Week 1) pre-dose assessment, or Day -7 
(Visit 1, Week -1), if missing. For participants randomized to 
Sequence 2, Baseline is the Day 85 (Visit 15, Week 13) pre-dose 
assessment, or Day 1 (Week 3, Visit 1), if missing.  
Note that if a dose of study medication was not received at Visit 3, or 
Visit 15 (dependent upon the participant), but the ADA assessment 
was performed at Visit 3 or Visit 15, this assessment would still be 
used as the Baseline assessment. 
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5.1.1.4 
Treatment Assignment and Treatment Group 
Table 5-3: 
Treatment Group Descriptions 
Treatment 
groups  
Full Description 
Data Display 
Description 
Included data 
1 
Placebo  
PBO  
Sequence 2, Treatment Period 1, and 
Sequence 3, both Treatment Periods 
2 
Rozanolixizumab exposure 
up to12 weeks 
RLZ 12 weeks 
Sequence 1, Treatment Period 1, and 
Sequence 2, Treatment Period 2 
3 
Rozanolixizumab extended 
exposure from 12 to 24 
weeks 
RLZ 24 weeks 
Sequence 1, Treatment Period 2 
Table 5-4: 
Sequence Descriptions 
Sequences 
Full Description 
Data Display Description  
1 
Sequence 1: Rozanolixizumab 12 weeks in Treatment 
Period 1, rozanolixizumab 12 weeks in Treatment 
Period 2 
Seq1: RLZ 12w +RLZ 12w 
2 
Sequence 2: Placebo in Treatment Period 1, 
rozanolixizumab 12 weeks in Treatment Period 2 
Seq2: PBO+RLZ 12w 
3 
Sequence 3: Placebo in Treatment Period 1 and 
Treatment Period 2 
Seq3: PBO+PBO  
Table 5-5: 
Period descriptions 
Periods 
Full Description 
Data Display Description  
 
Pre-Screening 
Pre-Screening 
0 
Screening (Day -42 to Day -15) 
Screening 
1 
Run-In (Day -14 to Day -1) 
Run-In 
2 
Treatment Period 1 (Day 1 to Day 84) 
TP1 
3 
Treatment Period 2 (Day 85 to Day 168) 
TP2 
4 
Run-Out (Day 169 to Day 182) 
Run-Out 
5 
Safety follow-up (Day 183 to Day 218, note that if a 
participant withdraws prior to this point SFU will not 
take place between Day 183 and 218) 
SFU 
5.1.2 
 Changes to Protocol-Defined Analyses 
According to the protocol, the Baseline for each variable will be taken as the value measured 
prior to, but closest to, the treatment on Day 1 (Visit 3, Week 1). However, this rule is specific to 
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efficacy endpoint assessments only. For safety variables the Baseline will be the most recent 
value prior to the first dose in the Run-In period. The Baseline definitions for all endpoints are 
summarized in Section 5.1.1.3.  
According to the protocol, the mean 7-day pain and fatigue scores after 10 weeks of treatment 
will be used for the secondary efficacy endpoint analysis. However, it has been clarified in the 
SAP that this is based on 12 weeks of treatment (Visits 3-14 in Treatment Period 1, and Visits 
15-26 in Treatment Period 2). 
Per the protocol, as a secondary analysis strategy, dropouts will be imputed as if they belong to 
the placebo group, under the conservative assumptions that dropouts are due to a lack of drug 
efficacy. This analysis will not be produced for the CSR. 
5.1.3 
Protocol Deviations 
Important protocol deviations are a subset of protocol deviations that may significantly impact 
the completeness, accuracy, and/or reliability of the study data (primary or key secondary 
outcomes) or that may significantly affect a participant’s rights, safety, or well-being. 
The criteria for identifying such protocol deviations will be defined within the IPD specifications 
document. 
Important protocol deviations will be categorized as follows:  
• Inclusion/exclusion criteria deviations 
• Incorrect treatment or dose administered 
• Procedural non-compliance 
• Treatment non-compliance 
• Withdrawal criteria deviation  
All protocol deviations will be reviewed as part of the ongoing data cleaning and data evaluation 
process. All protocol deviations will be discussed at data cleaning meetings for identification of 
individual IPDs and will be classified by the deviation types in the IPD document. IPDs 
identified at the data cleaning meetings will be listed by planned treatment sequence for the RS 
and will include the period of onset, deviation type and description. The period of onset of IPDs 
is derived per the rules stated in Appendix 4 Section 8.4. All IPDs will be summarized by 
treatment group and period.  
At least one Data Evaluation Meeting (DEM) will be performed prior to unblinding for the Early 
Readout Analysis. During this meeting, attendees will decide whether any study participants or 
data should be excluded from any of the analysis sets. A final DEM will be performed prior to 
database lock to confirm the analysis sets prior to the final analysis. The exclusion of any 
participants and the rationale will be clearly documented within the relevant TFLs.  
5.1.3.1 
COVID-19 Related Protocol Deviations  
UCB guidance on deviations and amendments related to SARS-CoV2 pandemic states that the 
identified COVID-19 related protocol deviations need to be reviewed on an ongoing basis in case 
they collectively or individually may give reason to consider a protocol amendment (for example 
study design changes or changes to primary analysis methods etc.).  
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Additionally, at data cleaning meetings and DEMs, entries on COVID-19 impact pages will be 
reviewed and assessed whether they are also IPDs. In this case, the COVID impacts will be 
queried to be reported on the protocol deviation log document. 
5.1.4 
 Handling of Dropouts or Missing Data 
Unless otherwise specified, there will be no imputation of missing data. 
For Pain and Fatigue NRS, the 7-day average scores will be calculated based on available data. If 
there are any missing records in the 7-day periods (inclusive of the assessment visit and the 
following 6 days), the scores will be calculated as the average amongst the recorded scores, 
ignoring the missing data. A minimum of 3 completed scores are required to calculate the 
average; otherwise, the average will be treated as missing. Missing data from visits associated 
with single assessments will not be imputed. 
For details regarding PK data, see Section 5.5.1. 
Handling missing or partial missing date and time described in Appendix 2, Section 8.2. 
5.1.5 
Handling Repeated and Unscheduled Measurements  
All repeated and unscheduled measurements will be presented in the data listings, where 
applicable. Repeated measurements are defined as more than one measurement at the same time 
point. Unscheduled and repeated measurements will not be used in the descriptive statistics 
unless otherwise specified. 
Assessments performed at the Early Withdrawal (EW) visit and which are within the protocol 
defined window of a scheduled visit will be assigned to that scheduled visit, and summarized 
accordingly. If any such data are already recorded at the given scheduled visit, data from the EW 
visit will not be re-mapped. Data will be re-mapped on a ‘per assessment’ basis where 
assessments are grouped as follows: 
• All hematology assessments 
• All clinical chemistry assessments 
• All urinalysis assessments 
• Vital signs assessments; systolic blood pressure, diastolic blood pressure, pulse rate and 
temperature) 
− Re-mapped vital signs assessments will be mapped to the pre-dose time point only. 
• Height and weight 
• All IgG assessments (total and subclasses) 
The grouping above defines which measurements will be retained together for any re-mapping. 
An individual parameter would not be re-mapped in isolation of the other parameters performed 
at the EW visit. For example, a measurement of diastolic blood pressure would only be re-
mapped together with the other vital signs assessments performed at the EW visit. If at least one 
data point is already available at the respective scheduled visit (eg, systolic blood pressure), the 
data at the EW will not be re-mapped. 
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Re-mapped EW visit data will be displayed in the by visit summary tables only if the assessment 
was planned for the particular visit.  
Assessments performed at the EW visit which are not within the protocol defined window of a 
scheduled visit will not be mapped to a scheduled visit and will be listed only.  
5.1.6 
Center Pooling Strategy  
The data from different centers will be pooled for TFLs. 
5.1.7 
Coding Dictionaries 
Adverse events and medical history will be coded using the latest available version of the 
Medical Dictionary for Regulatory Activities (MedDRA®) (Version 24.1). Medications will be 
coded according to the World Health Organization Drug Dictionary (WHO-DD) Global B3 
(Version 1 Mar 2021). Medical procedures will not be coded. 
5.2 
Study Population Characteristics  
5.2.1 
Participant Disposition 
Study participant disposition will be listed by planned treatment sequence for the ASP and will 
include the following information: study participant status (screen failure, completed or 
discontinued), date of informed consent, date of randomization, date and time of first and last 
dose of IMP (including during Run-In and Run-Out Periods), date of premature study 
termination (if applicable), and primary reason for study termination (if applicable). The listing 
will also include the date and reason for breaking the randomization code (if applicable) as well 
as the date of final contact for each study participant.  
Study discontinuations will be listed by planned treatment sequence for the RS and will include 
the reason for discontinuation and the period in which the participant discontinued. The period of 
discontinuation is derived as follows: 
• If a participant receives a dose of IMP in the Run-In Period and withdraws prior to the first 
dose of IMP in Treatment Period 1, then the period of discontinuation is Run-In.  
• If a participant withdraws after starting Treatment Period 1 (defined as receiving a dose of 
IMP during Treatment Period 1) and prior to receiving a dose of IMP in Treatment Period 2 
or attending one or more visits between Visit 16 and 26, the period of discontinuation is 
Treatment Period 1.  
• If a participant withdraws after starting Treatment Period 2 (defined as receiving a dose of 
IMP during Treatment Period 2 or attending one or more visits between Visit 16 and 26) and 
prior to receiving a dose of IMP in Run-Out, the period of discontinuation is Treatment 
Period 2.  
• If a participant withdraws after starting Run-Out (defined as receiving a dose of IMP during 
Run-Out, or attending Visit 27 or Visit 28), and did not attend the end of treatment (EOT) 
visit, the period of discontinuation is Run-Out. 
The study discontinuation listing will also include the total number of days on study medication, 
calculated in the following way: 
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Total days on study medication = Date of the last dose of study medication (including Run-Out)– 
date of the first dose in the Run-In Period +1 day 
In addition, there will be separate listings for re-screened study participants, of participants who 
did not meet eligibility criteria, and of visit dates. 
Study participant disposition will be shown in tables. The number of participants who screened, 
the number of screen failures, and reasons for screen failure will be summarized overall (note: 
re-screened subjects will only be counted once). Additionally, the number of participants who 
completed the study, the number of participants who discontinued, and reasons for 
discontinuation of study will be summarized overall and by (planned) treatment sequence and 
period. The percentages for discontinuation will be calculated based on the number of 
participants that started each period. 
Study participant disposition will also be summarized by site and investigators using the ASP, 
showing first participant in, last participant out, the number of participants screened, and the 
number and percentage of study participants included in each of the RS, SS-r, SS-t, FAS, PKS 
and PDS, overall and for each planned treatment sequence.  
Discontinuation due to AEs and the disposition of analysis sets will also be tabulated. 
5.2.2 
Impact of COVID-19 on Study Visits 
A listing of visits impacted by COVID-19 will be presented for all participants based on the 
ASP. This will include visit, visit date, study day, impact category, relationship to COVID-19 
and the narrative of the event. Participants who discontinue treatment or stop study participation 
due to COVID-19 pandemic will be included in participant disposition summaries.  
The number and percentage of participants with visits impacted by COVID-19 for any reason 
will be summarized by planned treatment sequence and impact category (overall and for each 
category separately). The denominator for the percentages will be the number of participants in 
the RS. 
5.3 
Demographics and Other Baseline Characteristics 
5.3.1 
Demographics 
All demographic characteristics will be summarized for the FAS and RS by treatment sequence 
and overall. The following continuous variables will be summarized using descriptive statistics: 
• Age at Screening (years) 
• Weight (kg) 
• Height (cm) 
• BMI (kg/m2) 
Body mass index in kg/m2 will be 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 following categorical variables will be summarized using frequency counts and percentages: 
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• Age (18-<65, 65-<85, ≥85 years) based on requirements for European Union Drug 
Regulating Authorities Clinical Trials (EudraCT) reporting 
• Age (≤18, 19-<65, ≥65 years) based on requirements for clinicaltrials.gov reporting 
• Weight (<100kg, >=100kg) 
• BMI (<30 kg/m2 and ≥30 kg/m2) 
• Gender 
• Race 
• Ethnicity 
• Country 
A listing of demographics by study participant and planned treatment sequence will be presented 
for the ASP. This will include participant ID, the year of birth, country, age at Screening (in 
years), gender, race, ethnicity, height (cm), weight (kg) and body mass index (BMI) at 
Screening. 
5.3.2 
Other Baseline Characteristics 
Descriptive statistics of BPI-SF Interference, Fatigue and Pain NRS and FIQR Baseline scores 
will be summarized by planned treatment sequence. Additionally, time (year) since diagnosis and 
time (year) since first symptoms of FMS based on the Screening date will be summarized in 
years using the SS-r (see Appendix 2 Section 8.2.4  for details on how to handle partial dates). 
Time since diagnosis and time since first symptoms of FMS will also be listed.  
5.3.3 
Medical History  
Medical history and ongoing medical conditions will be listed for the RS and summarized for the 
SS-r by planned treatment sequence and overall, MedDRA system organ class (SOC) and 
preferred term (PT). The reported term will be included in the listing. The summary will include 
the number and percentage of study participants and will be sorted alphabetically by SOC, High 
Level Group Term (HLGT) and, within HLGT, by descending incidence of PT, based on the ‘All 
Participants’ column. Family medical history collected for PDILI events will be listed.  
5.3.4 
History of Headache 
A listing of the history of headache responses will be presented by planned treatment sequence 
for the SS-r. 
5.3.5 
Medical History on Pain Management Programs 
A by participant listing of the information collected on the medical history of pain management 
programs electronic case report form (eCRF) will be presented by planned treatment sequence 
for the SS-r.  
5.3.6 
Prior and Concomitant Medications  
Prior and concomitant medications will be classified in the below categories. Past medications 
are a subset of prior medications. 
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Prior medications include medications that started prior to the first dose of IMP in Run-In. This 
includes Pre-Screening medications which are received prior to the date of Screening and 
includes any medications that started prior to dosing in Run-In and continued after the first dose 
in Run-In (prior and concomitant). 
 Concomitant medications include any medications that have been taken at least once on or after 
the date of first administration of IMP in Run-In. Permitted concomitant medications are limited 
to those listed in Section 6.5.1 of the protocol.  
Based on the above definitions a medication may be considered as both prior and concomitant.  
Prior and concomitant medications will be listed for the SS-r by planned treatment sequence and 
will include WHO-DD Anatomical Main Group [Level 1 term text], Pharmacological Subgroup 
[Level 3 term text], PT and reported term where applicable. All periods for which medication 
was received will be included in the listing. Periods are assigned based on whether a participant 
entered the given period. Full details of the rules for period assignment are described in 
Appendix 4 Section 8.4.2  
Prior medications will be summarized by planned treatment sequence for the SS-r and will 
include WHO-DD Anatomical Main Group [Level 1 term text], Pharmacological Subgroup 
[Level 3 term text] and PT. This table will include all medications that started and stopped prior 
to the first dose of IMP in Run-In and medications that started prior to and continued after the 
first dose of IMP in Run-In.  
Concomitant medications will be summarized by treatment group and period for the SS-r and 
will also include WHO-DD Anatomical Main Group [Level 1 term text], Pharmacological 
Subgroup [Level 3 term text] and PT.  
5.3.7 
Prior and Concomitant Medical Procedures 
Prior and concomitant medical procedures will be classified in the below categories. 
Prior medical procedures are defined as procedures occurring prior to the date of informed 
consent. 
Concomitant medical procedures are defined as procedures occurring on or after the date of 
informed consent.  
Prior and concomitant medical procedures will be listed only. The listing will contain the date of 
procedure and the period of onset. For the purpose of assigning the medical procedure to a 
category and to define the period of onset, partial and missing start dates will be imputed based 
on the rules defined in Appendix 2 Section 8.2.3. Medical procedures will be assigned to a 
period based on the date of the procedure. 
5.4 
Measurements of Treatment Compliance 
As dosing is performed in-house by the investigator or member of staff, no specific assessment 
of compliance is warranted. Any dosing deviation will be addressed in the DEM and described in 
the CSR.  
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5.5 
Pharmacokinetics and Pharmacodynamics 
5.5.1 
Pharmacokinetics 
All pharmacokinetic summaries will be presented using the PKS and listings will be presented 
based on the SS-r. PK samples from study participants on placebo will not be analyzed. 
Consequently, participants randomized to Sequence 3 will be excluded from the analyses 
described in this section and will not be included in TFLs. PK samples taken prior to the 
intended dose will be associated with the relevant dose for the purpose of tables and analyses. 
Samples taken after intended dose will be excluded from the analysis.  
The listing of plasma concentrations will include treatment sequence, visit, actual blood 
sampling time (presented as time relative to the start time of dosing of the respective visit), 
scheduled sampling time, and days since the previous dose. 
The plasma concentrations of rozanolixizumab at each scheduled assessment will be summarized 
by treatment group and period using descriptive statistics and presented in the form of table and 
figures. In addition, individual plasma concentrations will be shown in a figure by participant 
and actual time since the time of first active dose. 
The following rules will apply for PK data listings and summaries: 
• Values below the LLOQ will be reported as BLQ. 
• Descriptive statistics of concentrations will be calculated if at least 2/3 of the concentrations 
are quantified at the respective time point.  
• Values that are BLQ will be replaced by the numerical value of the LLOQ/2 (0.1ug/mL). 
• The 95% CI lower and 95% CI upper will be left blank if the SD (or equivalently, the  
geoCV) is 0 
• The geometric coefficient of variation (CV) is calculated as sqrt (exp(std ln^2)-1)*100, 
where std ln is the standard deviation of the log-transformed data. 
 
5.5.2 
Pharmacodynamics  
Venous blood samples will be collected for measurement of total serum IgG and subclass IgG 
concentrations as PD assessments. The observed concentration, change and percent change from 
Baseline in total serum IgG and IgG subclasses will be listed. The listings will also report the 
maximum change and maximum percent change from Baseline in each Treatment Period, based 
on the maximum decrease or smallest increase if no decrease is observed. 
The observed concentration, change and percent change from Baseline, and maximum change 
and percent change, in total serum IgG and IgG subclasses will be summarized for each planned 
treatment sequence on the PDS.  
The observed concentration, change and percent change from Baseline in total serum IgG and 
IgG subclasses will be summarized by each assessment for each treatment group on the PDS. 
There will be three treatment groups: placebo, rozanolixizumab for up to 12 weeks [Sequence 1, 
Period 1 and Sequence 2, Period 2], or rozanolixizumab given beyond 12 weeks [Sequence 1, 
Period 2].  
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The observed concentration and percent change from Baseline in Total IgG will be summarized 
by each visit by planned treatment sequence and Baseline body weight categories (<100kg, and 
>=100kg). 
The observed Baseline Total IgG, and the maximum percent change from Baseline for each 
Treatment Period will be summarized by planned treatment sequence and the Baseline body 
weight categories (<100kg, and >=100kg). 
For the purpose of calculating change from baseline or for descriptive statistics, BLQ values will 
be imputed with half of the lower limit of quantification (LLOQ). 
Median percent change from Baseline values in Total IgG will be plotted against study week for 
the entire study duration, by planned treatment sequence.  
Median percent change from Baseline values in Total IgG will be plotted against assessment 
number (1-4 within the given treatment period), by treatment group.  
Median percent change from Baseline in total IgG will be plotted against study week for the 
entire study duration, by planned treatment sequence and Baseline body weight categories 
(<100kg, and >=100kg). 
Spaghetti plots will be provided for Total IgG and percent change from Baseline in Total IgG 
over time stratified by treatment sequence. 
For correlation analysis between clinical endpoints and PD data, scatterplots including regression 
lines and Pearson correlation coefficients will be provided for change and percent change from 
Baseline at Visit 15 (or Visit 27) in total IgG versus:  
• Change from Baseline at Visit 15 and Visit 27 in BPI-SF interference. 
• Change from Baseline at Visit 13 and Visit 25 for FIQR 
• Change from Baseline based on the average score at Visit 14 and Visit 26 and the following 
6 days, for pain NRS and fatigue NRS.  
Scatterplots will be summarized by treatment group.  
Boxplots of maximum change and percent change from Baseline for Total IgG will also be 
plotted by sequence and period, for a total of 6 box plots.  
All pharmacodynamic summaries and figures will be presented based on the PDS, and listings 
will be presented using the SS-r.  
5.6 
Safety Analysis 
Overall safety summaries and listings will be performed using the SS-r. AE tables will be 
summarized using SS-t.  
5.6.1 
Extent of Exposure 
Administration of treatments will be listed by participant and planned treatment sequence. The 
listing will include the actual and planned treatment received, start and stop date and time of 
drug administration, total volume of treatment given, and site of injection (L/R side of the body 
and upper/lower abdomen).  
Study medication duration will be calculated in two ways: 
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• For the entire study duration (in days): 
− Calculated as the date of last dose of IMP (including Run-Out) - date of first dose of IMP 
in the Run-In Period + 1. 
• For Treatment Periods 1 and 2 only (in days): 
− Calculated as the date of the last dose of IMP (excluding Run-Out) – date of first dose of 
IMP in Treatment Period 1 +1.  
Study medication durations will be summarized by sequence using descriptive statistics. 
An additional summary of the number of infusions received in Treatment Periods 1 and 2 will 
also be generated. The following summaries will be generated based on the SS-r, by planned 
treatment sequence: 
• Number of infusions received as continuous and using the following categorical values: 1-4, 
5-8, 9-12, 13-16, 17-20, and 21-24;  
• Number of infusions received excluding mock infusions, using similar approach as the point 
above. 
An additional by participant listing of the exposure to IMP will be generated.     
5.6.2 
Adverse Events 
All AEs will be coded using MedDRA® and characterized as pre-treatment and treatment-
emergent according to the intake of each treatment. Adverse events with a start date prior to the 
first dose of IMP in the Run-In Period will be defined as pre-treatment AEs. A TEAE is defined 
as any AE with a start date on or after the first dose of IMP in Run-In, and on or before the 
earliest of the following: the last date of infusion (including Run-Out, if applicable) +56 days, 
final contact date or death. A TEAE is also defined as any unresolved event already present 
before administration of treatment that worsens in intensity following exposure to the treatment.  
Adverse events will be summarized by treatment period and treatment group based on the SS-t. 
If a participant receives an incorrect treatment  per the randomization schedule, the participant 
will be excluded from the summaries, and the AEs for this participant will be listed only. In such 
cases these will be noted in the footnotes for the relevant tables. Pre-treatment AEs will not be 
included in any summaries.    
 Adverse events will be assigned to the respective treatment period and treatment group based on 
the start date of the AE. The assignment of AEs to a given treatment period is summarized in 
Appendix 4 Section 8.4. The treatment groups will be summarized per treatment period in the 
following way: 
•  Run-In: 
− PBO (All 3 sequences) 
• Treatment Period 1 
− RLZ (Sequence 1) 
− Pooled PBO (Sequence 2 and 3) 
• Treatment Period 2 
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− RLZ/RLZ (Sequence 1) 
− PBO/RLZ (Sequence 2) 
− PBO/PBO (Sequence 3) 
• Run-Out and SFU (pooled) 
− RLZ/RLZ (Sequence 1) 
− PBO/RLZ (Sequence 2) 
− PBO/PBO (Sequence 3) 
The total N within the summary tables will correspond to the number of participants randomized 
to the respective treatment sequence who receive at least one dose of IMP in the given treatment 
period or who entered the SFU period. 
For details regarding partial dates, see Appendix 2 Section 8.2.  
The number and percentage of participants who experience TEAEs will be summarized by 
MedDRA™ SOC, HLT, and PT as described above.  
         Summaries of TEAEs will include the following:  
• Incidence of overall TEAEs (overview including number and percentage of study participant 
with any TEAEs, serious TEAEs, discontinuations due to TEAEs, permanent withdrawal of 
study medication due to TEAEs, drug related TEAEs, severe TEAEs and TEAEs leading to 
death; event counts will also be included) 
• Incidence of any TEAEs 
• Incidence of any serious TEAEs 
• TEAEs leading to permanent withdrawal of IMP 
• Incidence of severe TEAEs  
• Incidence of treatment-related TEAEs  
• Incidence of TEAEs by maximum causal relationship with IMP 
• Incidence of TEAEs by maximum intensity 
• Incidence of serious TEAEs by maximum causal relationship with IMP 
• Incidence of serious TEAEs by causal relationship  
• Incidence of fatal TEAEs by causal relationship with IMP 
• Incidence of non-serious TEAEs above reporting threshold of 5% of study participants 
− For the purpose of this table, the 5% reporting threshold will be considered based on all 
TEAEs reported within each of the following groups: 
◦ 
PBO Run-In  
◦ 
PBO Treatment Period 1 
◦ 
RLZ Treatment Period 1 
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◦ 
PBO/PBO Treatment Period 2, Run-Out, SFU 
◦ 
PBO/RLZ Treatment Period 2, Run-Out, SFU 
◦ 
RLZ/RLZ Treatment Period 2, Run-Out, SFU 
ie, non-serious TEAEs occurring with incidence >5% within any of the above groups will 
be included.  
• Incidence of drug-related TEAEs (overview including number and percentage of study 
participant with any drug-related TEAEs, serious drug-related TEAEs, discontinuations due 
to drug-related TEAEs, permanent withdrawal of study medication due to drug-related 
TEAEs, severe drug-related TEAEs and drug-related TEAEs leading to death; event counts 
will also be included) 
• Incidence of drug-related TEAEs by preferred term  
• Incidence of serious drug-related TEAEs by preferred term 
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.  
In summaries including intensity, the following intensity categories will be summarized: ‘Mild’, 
‘Moderate’, ‘Severe’. Participants who experience the same event multiple times will be 
included in the most severe category for tabulations by maximum intensity. Events with missing 
intensity will be considered as ‘Severe’ events for summary purposes but recorded as missing in 
the listings.  
Adverse event summaries will be sorted in the following way: 
• For Run-In: 
− Sort by alphabetical SOC and HLT within SOC. Within SOC and HLT within SOC, sort 
by descending frequency of PT in Run-In.  
• For Treatment Period 1 and Treatment Period 2: 
− Sort by alphabetical SOC and HLT within SOC. Within SOC and HLT within SOC, sort 
by descending frequency of PT in the RLZ/RLZ (Treatment Period 2) group. In the case 
of ties, sort these alphabetically within the RLZ/RLZ (Treatment Period 2) group.  
• For Run-Out and SFU group:  
− Sort by alphabetical SOC and HLT within SOC. Within SOC and HLT within SOC, sort 
by descending frequency of PT in the RLZ/RLZ group. In the case of ties, sort these 
alphabetically within the RLZ/RLZ group 
All listings will be presented by planned treatment sequence and will include study participant, 
SOC/HLT/PT/reported term, the onset date and outcome date of the event, the Treatment Period 
of onset, most recent actual treatment received, days since the most recent dose (derived), the 
event duration (derived), days since the first dose in the Run-In Period (derived), days since the 
first dose in Treatment Period 1 (derived), pattern of event, flag for a serious event, intensity, 
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relationship, action taken, AESM flag, AESI flag, Adverse Event of Focus (AEOF) flag, and 
outcome, unless specified. 
The following listings of AEs and TEAEs will be provided: 
• All AEs 
• All TEAEs 
5.6.3 
   COVID-19 AEs 
Confirmed COVID-19 cases will be recorded as AEs and will be reported under the AE section. 
An overall summary of TEAEs related to COVID-19 will be provided. This summary table will 
include the number and percentage of participants, as well as event counts, with any TEAE, any 
TEAE related to study drug, any severe TEAE, any severe TEAE related to study drug, any 
TESAE, any TESAE related to study drug, any TEAE leading to treatment discontinuation, any 
study drug related TEAE leading to treatment discontinuation, any TEAE leading to study 
withdrawal, and any deaths. In addition, to the above summary, TEAEs related to COVID-19 
will be summarized by SOC, HLT, and PT in a separate table. Both COVID-19 AE tables will be 
summarized by treatment period and treatment group based on SS-t.  
MedDRA has a COVID-19 Standardised MedDRA Query (SMQ). The query used in this study 
will be the broad MedDRA COVID-19 SMQ as defined at the specified analysis time points (see 
https://www.meddra.org/COVID-19-terms-and-MedDRA). 
5.6.4 
AEs of Special Interest and AEs of Special Monitoring 
An AE of special interest (AESI) listing will be produced of Potential Hy’s Law, defined as 
≥3xULN alanine aminotransferase (ALT) or aspartate aminotransferase (AST) with coexisting 
≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase (ALP), by treatment 
sequence and participant including most recent treatment received prior to the AE.  
An AE of special monitoring (AESM) is a product-specific AE, adverse reaction, or safety topic 
requiring special monitoring by UCB. AESM will be listed.  
Following events will be listed under AESM  
• Severe and/or serious headache 
• Suspected aseptic meningitis  
Summaries of the incidence of AESM and incidence of AESI will be generated. AESM and 
AESI summaries will be based on investigator assessment as recorded on the eCRF and 
confirmed during data review.  
5.6.5 
Adverse Events of Focus (AEOF)  
Rozanolixizumab treatment-emergent adverse events of focus (AEOF) include the following 
categories: 
• Headaches 
• Possible aseptic meningitis 
• Gastrointestinal disturbances 
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• Hypersensitivity reactions 
• Anaphylactic reactions 
• Injection site reaction 
• Infections 
• Opportunistic infections 
• Effects on the kidney 
• Drug related hepatic disorders 
• Effect on lipids 
Further details are described in Section 8.3.  
A by-participant listing of all treatment-emergent AEOF by category (as listed above) will be 
provided. The number and percentage of study participants who experience each treatment-
emergent AEOF will be summarized by treatment period and treatment group based on the SS-t. 
The following tables will be presented: 
• 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 
Note that each of the AEOF categories will be tabulated independently, eg, for the overall 
incidence summary, there will be one page showing the incidence of headaches, one page 
showing incidence of gastrointestinal disturbances, one for hypersensitivity reactions, etc.  
5.6.6 
Clinical Laboratory Evaluations  
All laboratory results values (clinical chemistry and hematology) will be listed by study 
participant, planned treatment sequence, time point and parameter. Changes from Baseline for 
numeric variables, the reference ranges and a flag to indicate whether values are below the lower 
limit of the reference range or above the upper limit of the reference range will be presented.  
Separate listings of all clinical chemistry and hematology laboratory results for participants who 
had at least one treatment-emergent marked abnormality (as defined in the abnormality criteria in 
Section 8.1.1 ) during the study will be presented. 
Urinalysis results will be listed for all study participants by treatment sequence, and will include 
changes from Baseline for numeric variables, and the reference ranges (if applicable). 
Any additional laboratory variables which were not collected for screening eligibility and are not 
included in the outputs described previously will be listed separately for all time points collected. 
These will include the following:  
• Serology 
• Serum pregnancy test (for women of childbearing potential, if taken post screening) 
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• Urine pregnancy tests 
• Urine toxicology screen (if taken post screening) 
• IGRA assessments  
• COVID-19 testing (for participants enrolled under Protocol Amendments 1 and 2 only) 
Clinical chemistry and hematology parameters will be summarized by planned treatment 
sequence and periods and time point for both absolute values and changes from Baseline. 
Summaries will be based on the SS-r.  
Treatment-emergent marked abnormalities with abnormalities defined in Appendix 1 
Section 8.1.1 will be summarized by clinical chemistry and hematology groups, planned 
treatment sequence and visit. Treatment-emergent here refers to measurements obtained on or 
after the date of the first dose of IMP in Run-In, and on or before the earliest date of the 
following: the last infusion (including Run-Out if applicable) +56 days, final contact date, or 
death, and which did not meet the abnormality criteria at Baseline. 
Measurements that are below the limit of quantification (BLQ) or above the limit of 
quantification (ALQ) will be presented as received in the listings. For the purpose of calculating 
change from baseline or for descriptive statistics, BLQ values will be imputed with half of the 
lower limit of quantification (LLOQ) and ALQ values will be imputed to the upper 
quantification limit (ULOQ). 
5.6.7 
Vital Signs  
The following vital signs measurements will be assessed: 
• Systolic and diastolic blood pressure  
• Pulse rate 
• Body temperature (oral, tympanic or axillary) 
• Body weight  
Vital signs assessment values and changes from Baseline will be summarized by planned 
treatment sequence, period, and time point where applicable, based on the SS-r. The time points 
summarized will be per Protocol Amendment 3. Therefore, any assessments completed by 
participants enrolled under any prior version of the protocol which are not required under 
Protocol Amendment 3, will be listed only.  
Vital signs measurements will be listed by planned treatment sequence, period, and time point 
including changes from Baseline and details of abnormal values. Body weight will be listed only.  
Treatment-emergent vital signs abnormalities defined as in Appendix 1, Section 8.1.2 will be 
summarized by planned treatment sequence, period and by time point as applicable.  
5.6.8 
Electrocardiograms (ECG)  
The following ECG parameters will be reported:  
• Heart rate 
• PR interval  
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• RR interval 
• QT interval  
• QRS interval  
• QTc interval (QT corrected for heart rate using Fridericia’s formula [QTcF])  
The individual measurements will be reported in the by-participant listings and will be presented 
by planned treatment sequence and time point. ECG findings will be listed separately. 
5.6.9 
    Other Safety Variable(s)  
5.6.9.1 
Physical examination  
Study participants with abnormalities in the physical examination at Screening will be listed by 
planned treatment sequence for the SS-r including details of the abnormality.  
5.6.9.2 
Neurological Examination 
In study participants who report severe and/or serious headache or suspected aseptic meningitis 
at the clinic visit, a full neurological examination (including fundoscopy) should be performed. 
Neurological examination and fundoscopy results will be listed by planned treatment sequence.  
5.6.9.3 
Suicidal Risk Monitoring - C-SSRS 
Study participants will be monitored appropriately for suicidal ideation and behavior or any other 
unusual changes in behavior. Suicidality will be assessed by trained study personnel using the C-
SSRS (Columbia University Medical Center, 2008). This scale will be used for screening as well 
as to assess suicidal ideation and behavior that may occur during the study. Collected C-SSRS 
data will be listed by planned treatment sequence for participants where suicidal ideation or 
behavior has been reported. Module of the questionnaire, time point, question and the associated 
response will be listed for all the visit days where this questionnaire is collected. 
5.6.9.4 
Assessment of Tuberculosis and Tuberculosis Risk Factors 
TB will be evaluated via various assessments as specified below during the study. Findings for 
TB assessment performed during PE after screening will be reported as AEs. No separate TB 
listing or table will be produced for PE TB assessment.  
The TB questionnaire will not be reported. TB assessment by IGRA will be reported together 
with other laboratory parameters.  
No separate TB listing or table will be produced for IGRA TB assessment.  
TB assessment by chest X-ray or other assessments will not be reported.  
IGRA test conversions should be reported as AEs as described in the protocol. The AE term 
would need to be updated with final diagnosis once available.  
No specific listing will be provided for test conversion.  
Latent TB 
Any latent TB infection will be reported as an AE and graded appropriately as described in this 
protocol. No specific listing will be provided for Latent TB infection.  
Active TB or NTM infection 
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Study participants who develop active TB or NTM infection during the study (conversion 
demonstrated by IGRA) will be withdrawn from the study. The study participant will be 
immediately and permanently discontinued from the IMP. The study participant should complete 
the assessments outlined for the EOT/EW Visit and encouraged to enter the 5-week SFU Period. 
Confirmed active TB is always considered an SAE and will be reported in AE section.  
5.6.9.5 
Potential Drug-Induced Liver Injury (pDILI) 
The number and percentage of participants who meet one or more of the following pDILI criteria 
at any visit (including unscheduled visits) will be summarized by treatment period and treatment 
group, based on the SS-r: 
• Participants with at least one post-Baseline liver laboratory assessment 
• Incidence of potential hepatotoxicity with symptoms potentially associated with hepatitis or 
hypersensitivity 
• Incidence of potential hepatotoxicity with no symptoms potentially associated with hepatitis 
or hypersensitivity 
• Laboratory criteria for pDILI: 
− (AST or ALT >= 3 x ULN) and TBL >= 1.5 x ULN 
− (AST or ALT > = 3 x ULN) and TBL >= 2 x ULN 
− (AST or ALT >= 3 x ULN) and TBL >= 2 x ULN and ALP < 2 x ULN (Hy’s Law) 
In order to meet the above criteria, a study participant must experience the elevation in bilirubin 
and ALT or AST (and the absence of the ALP elevation) at the same visit. For example, a study 
participant who experiences a >=2xULN elevation of bilirubin at one visit and a >=3xULN 
elevation in ALT (or AST) at a subsequent visit has not fulfilled the Hy’s law criteria. If 
participant meets part of one criterion but at least one parameter is unknown, then he/she should 
not be considered for meeting the criterion. 
Additional analyses for liver function tests (LFTs) will be performed to assess the potential for 
liver toxicities in accordance with the United States Food and Drug Administration guidelines. 
Per guidelines, the following criteria will be used to define levels of LFT elevation: 
• Aspartate aminotransferase (AST): >3 x ULN, >5 x ULN, >8 x ULN, >10 x ULN, >20 x 
ULN 
• Alanine aminotransferase (ALT): >3 x ULN, >5 x ULN, >8 x ULN, >10 x ULN, >20 x ULN 
• AST or ALT: >3 x ULN, >5 x ULN, >8 x ULN, >10 x ULN, >20 x ULN 
• Total bilirubin (TBL): >1.5 x ULN, >2 x ULN 
• Alkaline phosphatase (ALP) >1.5 x ULN 
The number and percentage of study participants who meet one or more of the above LFT 
elevation criteria at any visit (including unscheduled visits) will be summarized by treatment 
period and treatment group, based on the SS-r.  
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A listing of results obtained for all scheduled and unscheduled visits will also be provided for 
study participants who meet at least one of the following criteria: 
• (ALT or AST>=3xULN) and (TBL >= 1.5 x ULN) 
• (ALT or AST>=3xULN) and (TBL >= 2 x ULN) and (ALP < 2 x ULN) 
The listing will show the new ratio, nR, calculated as the ratio of either ALT or AST (whichever 
is higher) to ALP, expressed as multiples of their ULN, ie, Max (ALT x ULN or AST x ULN) / 
ALP x ULN.  
5.7 
Immunogenicity 
The immunogenicity analysis will be summarized based on the SS-r by treatment sequence or by 
visit when applicable. Samples from study participants on placebo will not be tested for anti-drug 
antibodies (ADA). Consequently, participants randomized to Sequence 3 will be excluded from 
the analyses described in this section and will not be included in TFLs. 
Anti-drug antibodies will be measured using a three-tiered assay approach: screening, 
confirmatory and titration assay. Any sample confirmed positive for ADA will be assayed to 
determine whether there is neutralizing potential. 
Samples will first be evaluated in the screening assay (reported as ‘negative screen’ or ‘positive 
screen’), followed by analysis of screened positive samples in the confirmatory assay to confirm 
the true positivity of the samples (reported as ‘negative immuno-depletion’ or ‘positive immuno-
depletion’). Samples that are confirmed as positive in the confirmatory assay will be evaluated in 
a titration assay to quantify the ADA level and will be reported as titer (reciprocal dilution factor 
including minimum required dilution (MRD)).  
The ADA sample status will be determined for each pre-treatment (Baseline) and post-treatment 
(post-Baseline) visit where samples were taken for ADA analysis (both scheduled and any 
unscheduled visits):  
Table 5-6:  
ADA Sample Status 
ADA sample status 
Definition 
ADA negative (ADA-) 
Sample values that are either ‘negative screen’ or ‘positive screen’ and 
‘negative 
immuno-depletion’ 
if 
corresponding 
rozanolixizumab 
concentrations are equal or below the validated drug tolerance limit of the 
ADA assay (200ug/ml rozanolixizumab) allowing detection of 100 ng/ml 
ADA. 
Note that if an ADA sample does not have a corresponding PK sample (at 
the same visit), then it is assumed that the drug concentration is below the 
drug tolerance limit. 
ADA positive (ADA+) 
Sample values that are ‘positive screen’ and ‘positive immuno-depletion’  
ADA inconclusive 
Sample values that are either ‘negative screen’ or ‘positive screen’ and 
‘negative immuno-depletion’ but with corresponding rozanolixizumab 
concentrations  above the validated drug tolerance limit of the ADA assay 
(200ug/ml rozanolixizumab) allowing detection of 100 ng/ml ADA.  
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ADA sample status 
Definition 
Note that if an ADA sample does not have a corresponding PK sample (at 
the same visit), then it is assumed that the drug concentration is below the 
drug tolerance limit and therefore this sample cannot be classified as 
‘Inconclusive’. 
Missing  
Samples that were collected per schedule but could not be tested for ADA 
status due to inadequate sample volume, mishandling, or errors in sample 
collection, processing, storage, etc.  
Evaluable ADA sample 
A sample for which the sample status is not missing nor ADA inconclusive 
Neutralizing antibody (NAb) sample status (positive/negative/inconclusive/missing) will be 
determined for ADA positive samples. Samples that are NAb positive will be evaluated in a 
titration assay to quantify the NAb level and will be reported as titer. 
Definition of ADA Baseline 
The Baseline values for ADA will be based on the last measurement prior to receiving the first 
dose of rozanolixizumab. For participants randomized to Sequence 1, Baseline is the Visit 3 
(Week 1) pre-dose assessment, or Visit 1 (Week -1), if missing. For participants randomized to 
Sequence 2, Baseline is the Visit 15 (Week 13) pre-dose assessment, or Week 3 (Visit 1), if 
missing.  
ADA/NAb Participant Status 
The ADA/NAb participant status will be further classified on study participant level as outlined 
below (Shankar et al. 2014; Rup et al. 2015, Presentation Immunogenicity Summit, 2021, Joleen 
White, Enabling Clinical Immunogenicity Impact Assessment with Standardized Data Tabulation 
Models).  
The by-participant classifications for ADA status will be derived 3 times: 
• For the entire study duration (ie, including all samples from Treatment Periods 1 and 2, and 
SFU). Note that participants in Sequence 2 will not have samples from Treatment Period 1. 
• Based on RLZ 12 weeks exposure:  
− Sequence 1 Baseline (Visit 3) to Day 85 (Visit 15) 
− Sequence 2 Baseline (Visit 15) to Day 169 (Visit 27)   
• Based on RLZ 24 weeks exposure: 
− Sequence 1 Baseline (Visit 3) to Day 169 (Visit 27)   
Based on the above, participants in Sequence 1 will have 3 ADA classifications, and participants 
in Sequence 2 will have 2 ADA classifications. The combined ADA/NAb participant status will 
be derived only based on the ADA status for the entire study duration (ie, each participant will 
have only 1 ADA/NAb classification). 
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The ADA participant status is composed of 6 individual categories: ADA negative, inconclusive, 
and ADA positive whereby a positive participant’s status is further subdivided into treatment-
induced, treatment boosted, or non-treatment-emergent ADA positive.  
However, the ADA participant status as defined in category 1 (ADA-NEG) can only be applied 
for participants having 2/3 (66.6%) of the protocol scheduled post-baseline ADA samples 
‘evaluable’, (ie, neither missing as per schedule nor inconclusive) which is equivalent to the 
following:  
• For the entire study duration 
− For Sequence 1, a minimum of 6/8 samples 
− For Sequence 2, a minimum of 4/5 samples 
• RLZ 12 weeks 
− For Sequence 1, a minimum of 2/3 samples 
− For Sequence 2, a minimum of 2/3 samples 
• RLZ 24 weeks 
− For Sequence 1, a minimum of 4/6 samples 
Study participants that have a positive baseline value and no post-baseline values collected will be 
categorized as categories 2 (ADA-POS) and 5 (Non-TE-POS). 
For a dropout participant, the participant status would be evaluated on the basis of the sample 
collection compared to all anticipated protocol scheduled samples assuming that they had actually 
completed the study.  
Table 5-7:  
ADA Participant Status Categories 
Term 
Definition 
 
Category 
ADA participant status categories 
ADA-NEG (Pre ADA 
negative – treatment 
induced ADA negative) 
Study participants who have negative ADA sample status at 
baseline and at all sampling time points post-baseline with 
the number of evaluable samples (non- missing per 
schedule nor inconclusive) more or equal to 2/3 as defined 
above. 
 
[Note: study participants with baseline samples missing and 
negative ADA status at all sampling time post-baseline are 
included in this category; based on the following rationale: 
in case the participant would be pre-Ab positive, the 
participant is expected to present ADA positive samples 
post-baseline]  
1 
ADA-POS  
Study participants who have a positive ADA sample status 
at any time point (either Baseline, or post-Baseline)  
2 
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Term 
Definition 
 
Category 
TI-POS (Pre ADA 
negative – Treatment 
Induced ADA positive) 
Study participants who have a negative ADA status at 
baseline and positive ADA status at any sampling point 
post-Baseline. 
3 
TB-POS (Pre ADA 
positive – Treatment 
Boosted ADA positive) 
Study participants who have a positive ADA status at 
baseline and positive ADA status at any sampling point 
post-baseline with non-missing increased titer values 
compared to baseline (>fold difference from Baseline value 
as determined by the MSR of the assay). 
 
4 
Non-TE-POS (Pre-ADA 
positive- Non-Treatment -
Emergent ADA positive)  
 
Study participants who have a positive ADA status at 
baseline and 1) negative ADA status at all evaluable 
sampling points post-baseline or 2) positive ADA status at 
any evaluable sampling points post- baseline with non-
missing titer values of the same or lower magnitude as 
baseline (≤ fold difference from Baseline value as 
determined by the MSR of the assay). 
 
5 
Inconclusive 
Study participant for who the ADA participant status 
cannot be defined due to missing or inconclusive samples. 
Inconclusive [1]: Study participant that had negative ADA 
status at baseline and post-baseline samples missing per 
schedule or inconclusive that is higher than the % allowed 
as defined above, while others post-baseline samples are 
ADA negative up to the time point of interest.  
Inconclusive [2]:  Participants who do not satisfy any of the 
above criteria. 
6 
Combined ADA participant status categories 
TE-POS (TE ADA positive) 
Includes study participants defined in category 3 and 4 
7 
Treatment emergent ADA 
positive – NAb positive 
(TE-POS, NAb-POS) 
Study participants in category 7 who have at least one NAb 
positive sample 
8 
Treatment emergent ADA 
positive – NAb negative 
(TE-POS, NAb-NEG) 
Study participants in category 7 who have no NAb positive 
samples 
9 
Non-treatment emergent 
ADA positive–- NAb 
positive (Non-TE-POS, 
NAb-POS) 
Study participants in category 5 who have at least one NAb 
positive sample 
10 
Non-treatment emergent 
ADA positive–- NAb 
negative  (Non-TE-POS, 
NAb-NEG) 
Study participants in category 5 who have no NAb positive 
samples 
11 
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The fold difference increase from baseline value, ie, the minimum significant ratio (MSR) 
determined during assay validation, will be reported in the relevant tables, listings and figures. It 
reflects the fold difference in titer level that considered higher than the assay variation in titer 
determination. 
Calculation of Fold Increase for use of MSR, and for classifying ‘Non-TE-POS (Pre-ADA 
positive- Non-Treatment-Emergent ADA positive)’ and ‘TB-POS (Pre ADA positive – 
Treatment Boosted ADA positive)’ category: 
Fold increase= post-dose titer/baseline titer 
 The following summaries, figures and listings will be produced and will be presented using the 
SS-r: 
Tables: 
• Summary table displaying the number and percentage of study participants with a positive 
ADA, negative ADA, inconclusive or missing ADA sample status at the time of each visit by 
planned treatment sequence.  
• Summary table displaying the number and percentage of study participants with a positive 
NAb, negative NAb, inconclusive or missing NAb sample status at the time of each visit by 
planned treatment sequence.  
• Number and percentage of study participants in each of the individual and combined ADA 
participant status categories and combined categories (1-11) presented in Table 5-7 for each 
time period specified above. The denominator will be the total number of study participants 
with an individual ADA participant category defined for each time period.  
• Total prevalence of pre-existing ADA and NAb, defined as number and percentage of 
participants having an ADA/NAb positive sample status at baseline, with the denominator 
being the total number of study participants having an evaluable ADA/NAb sample result at 
baseline. 
• The first occurrence of treatment-emergent ADA positivity: cumulative number and 
percentage of TE-ADA positive participants (category 7) who are ADA positive for the first 
time based on samples collected over the entire study duration, including SFU.  
• Summary table of mean maximum percentage change from Baseline in total IgG summarized 
by ADA participant categories (1-6) for the following: 
− Sequence 1, Treatment Period 1 (RLZ 12 weeks) using ADA participant category based 
on RLZ 12 weeks exposure and maximum percent change from Baseline in total IgG in 
Treatment Period 1. 
− Sequence 2, Treatment Period 2 (RLZ 12 weeks) using ADA participant category based 
on RLZ 12 weeks exposure and maximum percent change from Baseline in total IgG in 
Treatment Period 2. 
− Sequence 1, Treatment Period 1 and Treatment Period 2 (RLZ 24 weeks) using ADA 
participant category based on RLZ 24 weeks exposure and maximum percent change 
from Baseline in total IgG in Treatment Period 2 
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− Sequence 1 Treatment Period 1 and Sequence 2, Treatment Period 2 (RLZ 12 weeks) 
using ADA participant category based on RLZ 12 weeks exposure and maximum percent 
change from Baseline in total IgG in Treatment Period 1 for Sequence 1, and Treatment 
Period 2 for Sequence 2. 
• Summary table of mean change from Baseline in BPI-SF Interference score in Treatment 
Periods 1 and 2, summarized by ADA participant categories (1-6) for the following: 
− Sequence 1, Treatment Period 1 (RLZ 12 weeks) using ADA participant category based 
on RLZ 12 weeks exposure and change from Baseline in BPI-SF interference score at 
Visit 15.  
− Sequence 2, Treatment Period 2 (RLZ 12 weeks) using ADA participant category based 
on RLZ 12 weeks exposure and change from Baseline in BPI-SF interference score at 
Visit 27. 
− Sequence 1, Treatment Period 1 and Treatment Period 2 (RLZ 24 weeks) using ADA 
participant category based on RLZ 24 weeks exposure and change from Baseline in BPI-
SF interference score at Visit 27. 
− Sequence 1 Treatment Period 1 and Sequence 2, Treatment Period 2 (RLZ 12 weeks) 
using ADA participant category based on RLZ 12 weeks exposure and change from 
Baseline in BPI-SF interference score at Visit 15 for Sequence 1, and Visit 27 for 
Sequence 2. 
• Overall summary table of TEAEs summarized by ADA participant categories 1, 5, 6, and 7 
where the participant category is based on ADA data for the entire study duration. This table 
will include the following: 
− Sequence 1 – all TEAEs occurring on or after the first dose in Treatment Period 1, up to 
the SFU Visit.  
− Sequence 2 – all TEAEs occurring on or after the first dose in Treatment Period 2, up to 
the SFU Visit.  
• Summary table of incidence of TEAE by ADA participant category 1, 5, 6, and 7 for the 
where the participant category is based on ADA data for the entire study duration, as 
described for the overall summary table. This table will be repeated for the AEOF 
hypersensitivity reactions, anaphylactic reactions and injection site reactions (defined as 
AEOF in Section 13.7). 
    Figures: 
• Individual time course plots for ADA positive study participants, (within categories 3,4 and 
5) representing ADA and NAb titers (on log-scale), percentage change from Baseline for 
total IgG and change from Baseline for BPI-SF Interference Score. This will include the 
following: 
− For Sequence 1: All data from Visit 3 (ADA Baseline) to SFU, with the x-axis presented 
in weeks 
− For Sequence 2: All data from Visit 15 (ADA Baseline) to SFU, with the x-axis presented 
in weeks 
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• A plot of the median change from Baseline in Total IgG over time by cumulative ADA 
positivity status and planned treatment sequence. The ADA positive status will be considered 
in a cumulative manner at each time point (ie, if a participant has had at least one positive 
sample at any time point up to and including the given time point, that participant will be 
counted as positive at that time point, regardless of any subsequent negative measurements. 
In addition, if the Baseline sample is missing then the sample will be classified as being 
negative for the cumulative ADA status). This plot will include the following: 
− For Sequence 1: All data from Visit 3 (ADA Baseline) to SFU, with the x-axis presented 
in weeks 
− For Sequence 2: All data from Visit 15 (ADA Baseline) to SFU, with the x-axis presented 
in weeks 
• A plot of median percent change from Baseline in Total IgG over time by cumulative ADA 
positivity status and planned treatment sequence, as described above.  
• A box-and-whisker plot of maximum post-Baseline ADA titer (on log-scale) versus ADA 
participant category (where the participant category is based on ADA/NAb data for the entire 
study duration) for categories 8, 9, 10, and 11 by treatment sequence. The same plot will be 
repeated for NAb titer for ADA participant categories 8 and 10. 
• Time course plot of mean CFB in BPI-SF Interference score, summarized by ADA 
participant categories 1, 6, 8, 9, 10, and 11, where the participant category is based on 
ADA/NAb data for the entire study duration. Separate plots for each treatment sequence will 
be generated. 
− For both Sequence 1 and Sequence 2, BPI-SF Interference scores from Visits 7, 11, 15, 
19, 23 and 27 will be presented, with the x-axis presented in weeks. 
• Spaghetti plots of percentage CFB for total IgG, for each of the ADA participant categories 
1, 6, 8, and 9 (where the participant category is based on ADA/NAb data for the entire study 
duration). Individual samples that tested positive for ADA will be indicated on the plot. 
Separate plots for each treatment sequence will be generated.  
− For both Sequence 1 and Sequence 2, BPI-SF Interference scores from Visits 7, 11, 15, 
19, 23 and 27 will be presented, with the x-axis presented in weeks. 
• Scatterplot of individual change from Baseline in BPI-SF Interference score categorized by 
ADA titer tertile (including category ADA not present) for each scheduled assessment. The 
same plot will be repeated for NAb titer. Positive ADA/NAb samples that do not have an 
associated titer, will not be included in the plot. 
− For Sequence 1, ADA/NAb and BPI-SF data for Visits 11, 15, 23, and 27 will be 
displayed. 
− For Sequence 2, ADA/NAb and BPI-SF data for Visits 23 and 27 will be displayed. 
These visits will be overlaid with Visits 11 and 15 for Sequence 1, to reflect 12 weeks of 
exposure.  
• Scatterplot of individual percentage change from Baseline for total IgG categorized by ADA 
titer tertile (including category ADA not present) for each scheduled assessment. The same 
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plot will be repeated for NAb titer. Positive ADA/NAb samples that do not have an 
associated titer, will not be included in the plot. 
− For Sequence 1, ADA/NAb and BPI-SF data for Visits 4, 11, 15, 16, 23, and 27 will be 
displayed. 
− For Sequence 2, ADA/NAb and BPI-SF data for Visits 16, 24, and 27 will be displayed. 
These visits will be overlaid with Visits 4, 11, and 15 for Sequence 1, to reflect 12 weeks 
of exposure.  
Listings: 
• A listing of the by visit ADA/NAb results including the results from the screening assay, 
confirmatory assay, and titration assay (titer level), the fold change compared to baseline and 
the ADA/NAb sample status will be presented by planned treatment sequence and 
participant. This listing will also contain the time since the previous administration of IMP 
(in days). 
• A listing of the ADA and ADA/Nab participant categories will be presented by planned 
treatment sequence.  
− Participants randomized to Sequence 1 will have 3 ADA classifications (based on ADA 
data for the entire study duration, 12 weeks and 24 weeks), and 1 ADA/NAb 
classification (based on ADA/NAb data for the entire study duration) 
− Participants randomized to Sequence 2 will have 2 ADA classifications (based on ADA 
data for the entire study duration, and 12 weeks) and 1 ADA/Nab classification (based on 
ADA/NAb data for the entire study duration).  
• A listing of the by visit ADA and NAb sample status, ADA titer, NAb titer, rozanolixizumab 
plasma concentration, percentage change from Baseline for total IgG and IgG subclasses, and 
change from Baseline for BPI-SF Interference score will be presented.  
• A listing of the following TEAEs will be generated: 
− For participants randomized to Sequence 1 – all TEAEs occurring on or after the first 
dose in Treatment Period 1, up to the SFU Visit.  
− For participants randomized to Sequence 2– all TEAEs occurring on or after the first dose 
in Treatment Period 2, up to the SFU Visit.  
This listing will include the ADA and NAb sample status and ADA and NAb titers at the 
closest sampling time point to the date of onset of the TEAE (this could be prior to or after 
the date of onset). If both sampling points are equidistant to the TEAE, then the prior one is 
selected. 
 
5.8 
Efficacy Analysis 
The observed result and change from Baseline of each efficacy assessment (including the 
individual items as well as the summary scores) will be tabulated by planned treatment sequence 
and visit (including Screening and Run-In, if applicable), based on the FAS.  
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The observed result and change from Baseline of each efficacy assessment (including the 
individual items as well as the summary scores) will also be summarized by treatment group, 
based on the FAS. 
Mean change from Baseline (with 95% confidence intervals based on summary statistics) for 
BPI-SF and FIQR will be summarized by treatment sequence and period using a Forest plot. The 
BPI-SF plot will contain all BPI-SF interference questions as well as the BPI-SF interference 
score. The FIQR plot will include all individual questions as well as the domain scores and 
overall FIQR score. Plots will be based on the mean change from Baseline at Assessment 3 in 
each treatment period. 
Figures for mean change from Baseline over time will be generated for each efficacy parameter 
by treatment sequence over both Treatment Periods, and by treatment and period day. For the 
latter all combinations of treatment and sequence will be displayed separately (6 symbols per 
plot) and the periods will be superimposed. 
For the NRS measurement collected over multiple days, the average of the measurements related 
to a given visit will be summarized in the tables and figures, rather than the individual 
measurements. If two or more pain or fatigue NRS results are recorded on the same calendar day, 
the latest result of the day will be used for the purpose of calculating the average score, and for 
display in the summaries. All measurements will be presented in the listings and duplicate scores 
will be indicated as appropriate. 
5.8.1 
Derivations of Efficacy Variables(s) 
The different efficacy variables will have different Baseline and endpoint measurement time 
points, depending on when the relevant data is being collected. Table 5-8 gives details on the 
timing of these baseline and effect measurements.  
Table 5-8:  Efficacy endpoint time points  
Endpoint  
Baseline 
measurement 
Effect measurement for 
period 1  
Effect measurement for 
period 2  
BPI-SF interference 
(and other endpoints 
derived from BPI-
SF) 
start of Treatment 
Period 1 
Visit 3, D1 pre-dose 
pre-dose start of Treatment 
Period 2 
Visit 15, Week 13, D85  
(12 weeks of treatment) 
Run-Out visit 1  
Visit 27, Week 25, D169 (12 
weeks of treatment) 
Pain and fatigue 
assessment (NRS) 
Run-In visit 2 (starting 
at D-7 and going to D-
1) 
Visit 14, Week 12 
starting at D78 and going to 
D84  
(12 weeks of treatment) 
Visit 26, Week 24 
starting at D162 and going to 
D168  
(12 weeks of treatment) 
FIQR (and endpoints 
derived from the 
FIQR)  
Run-In visit 2 
Visit 2, D-7 
Visit 13, Week 11, D71 
(10 weeks of treatment) 
Visit 25, Week 23, D155 
(10 weeks of treatment) 
• BPI-SF interference score is calculated as the mean of the seven pain interference items 
of the BPI-SF questionnaire. The BPI-SF interference score will be calculated if more 
than 50%, of the total items have been completed on a given administration. For more 
details on BPI-SF see (Cleeland and Ryan, 1991). 
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• The FIQR is scored in 3 steps: 
o Step 1. Sum the scores of the items within each of the three domains (domain 1: 
activities, domain 2: overall impact, and domain 3: symptoms). 
o Step 2. Divide domain 1 score by three, domain 2 score is unchanged, and divide 
domain 3 score by two. (So if the scores in domains 1, 2 and 3 are 60, 9 and 40, 
respectively, then domain 1 score divided by three = 20; domain 2 remains 
unchanged at = 9; domain 3 score divided by two = 20) 
o Step 3. Add the three resulting domain scores to obtain the total Revised 
Fibromyalgia Impact Questionnaire (FIQR) score. In the example above the total 
FIQR score would be 20+9+20 = 49 
o Missing answers: For unanswered questions the following “weighting” factor 
should be used. If only x questions from the first section (function) were 
answered, one would weigh the summated score of the x questions by 9/x (as 
there are 9 items in the function set of questions) Likewise the second section 
(overall impact) would have a weighting of 2/x (there are only 2 items) and the 
third section (symptoms) would have a weighting of 10/x (there are 10 items). 
5.8.2 
Primary Efficacy Variable  
The primary efficacy endpoint is the average BPI-SF interference score after 12 weeks of 
double-blind treatment, adjusted for Baseline score.  
For the purpose of analysis, there will be three treatment groups: placebo, rozanolixizumab for 
up to 12 weeks [Sequence 1, Period 1 and Sequence 2, Period 2], or rozanolixizumab given 
beyond 12 weeks [Sequence 1, Period 2]. The main difference of interest is that between 
rozanolixizumab for up to 12 weeks and placebo. 
In order to estimate the mean difference in the average BPI-SF interference scores after 12 weeks 
of treatment, the BPI-SF interference scores measured at Visits 7, 11, 15, 19, 23, and 27 will be 
modelled using a longitudinal linear mixed effect model (LMM). The pre-dose value taken at the 
first visit of Treatment Period 2 (Visit 15) will be used as the measure of treatment effect after 12 
weeks of treatment for Period 1, while the pre-dose value taken at Run-Out Visit 27 will be used 
as the measure of treatment effect after 12 weeks of treatment for Period 2. Any BPI-SF 
assessments which are not completed within the protocol defined window of the scheduled visit 
will not be included within the primary efficacy analysis.  
5.8.2.1 
Primary Analysis of Primary Efficacy Variables(s) 
The LMM for the BPI-SF interference score will have treatment as a fixed effect and the study 
participant ID will be included as a random effect. 
The following additional fixed effects will be included: 
• Treatment Period (1 or 2) 
• assessment number within the period (1st, 2nd, or 3rd assessment categorical) number 
corresponding to Visit 7, 11, and 15 for Treatment Period 1, or Visit 19, 23, or 27 for Treatment 
Period 2) 
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• an interaction of treatment by assessment number 
• an interaction of assessment number-by-Treatment Period  
The following covariates will also be included: 
• BPI-SF interference scores at Baseline (taken at Visit 3, prior to dosing) 
The model can also be written as follows:  
𝑌𝑖𝑗= 𝑌𝑖,𝑏𝑙+ 𝑃𝑒𝑟𝑖𝑜𝑑𝑖𝑗+ 𝐴𝑠𝑠𝑒𝑠𝑠𝑚𝑒𝑛𝑡𝑖𝑗+ 𝑇𝑅𝑇+ 𝐴𝑠𝑠𝑒𝑠𝑠𝑚𝑒𝑛𝑡𝑖𝑗× 𝑇𝑅𝑇𝑖𝑗+ 𝑃𝑒𝑟𝑖𝑜𝑑𝑖𝑗× 𝐴𝑠𝑠𝑒𝑠𝑠𝑚𝑒𝑛𝑡
+ (1|𝑠𝑖) 
Where 𝑌 indicates the measurement of interest (BPI-SF interference score in this case), 𝑖 the i-th 
participant, 𝑗 the j-th observation for each participant, × indicate an interaction, and (1|𝑠𝑖) 
indicate the random intercept effect for participant i. 𝑌𝑖,𝑏𝑙 indicates the baseline value for 
participant i. Note that this model is specified as-is for conceptual clarity, but is over-
parameterized, which may need to be taken into account during model fitting.  
The model will utilize an unstructured covariance pattern for the repeated measures. If the model 
does not converge using the unstructured pattern, then an autoregressive covariance structure 
will be used. The Kenward-Roger approximation will be used to estimate the denominator 
degrees of freedom.  
The LS Means estimate for each of the treatments with 95% CI should be reported. LS Means 
should be estimated assuming assessment effects of assessment 3 and using the period effect for 
period 2. In addition, the LS Means estimate of the differences between rozanolixizumab 12 
weeks and 24 weeks, respectively, and placebo should be reported, using the same period and 
assessment effects as before.  
• Rozanolixizumab 12 weeks – Placebo 
• Rozanolixizumab 24 weeks – Placebo 
• Rozanolixizumab 12 weeks - Rozanolixizumab 24 weeks 
P-values for the baseline, treatment period, assessment number, treatment by assessment number, 
and treatment period by assessment number interaction terms will be reported. 
All study participants in the FAS with Baseline BPI-SF score and one or more post-Baseline 
assessments will be included in the model. 
Inter current event (ICE): Permanent discontinuation of treatment will be handled using a 
hypothetical strategy assuming that the study participants did not experience the events, with 
data following discontinuation excluded from analysis. 
In addition, summary statistics of all results at assessment number 3 (in Treatment Periods 1 and 
2) for all participants included in the model will be reported in the primary efficacy table by 
treatment group. 
5.8.2.2 
Secondary Analysis of Primary Efficacy Variable(s) 
As secondary analysis strategy, each period will be analyzed separately using a mixed effect 
model, with study participant as random effect and treatment, assessment number, treatment by 
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assessment number interaction, and Baseline as fixed effects. For Treatment Period 1, there will 
be 2 treatment groups: placebo and rozanolixizumab. For Treatment Period 2, there will be 3 as 
defined for the primary analysis. 
The LS Means estimate for each of the treatments with 95% CI should be reported, as well as the 
LS Means estimate of the differences between relevant treatment groups. See below treatment 
differences to be estimated at by period analysis.  
Treatment Period 1;  
• Rozanolixizumab 12 weeks – Placebo 12 weeks_Seq2 (between Seq1 and Seq2) 
• Rozanolixizumab 12 weeks – Placebo 12 weeks_Seq3 (between Seq1 and Seq3) 
• Rozanolixizumab 12 weeks – Placebo 12 weeks (between Seq1 and pooled placebo from 
Seq2 and Seq3) 
Treatment Period 2;  
• Rozanolixizumab 24 weeks – Placebo 24 weeks (between Seq1 and Seq3) 
• Rozanolixizumab 12 weeks - Rozanolixizumab 24 weeks (between Seq2 and Seq1) 
• Rozanolixizumab 12 weeks – Placebo (between Seq2 and Seq3) 
P-values for the baseline, assessment number, and treatment by assessment number interaction 
should also be reported.  
In addition, summary statistics of all results at assessment number 3 (in Treatment Period 1 and 
2, as appropriate) for all participants included in the model will be reported in the secondary 
analysis summary tables. 
5.8.3 
Supportive and Sensitivity Analyses of the Primary Efficacy Variable 
As a sensitivity analysis to evaluate the assumption of treatment effect being independent from 
site, site (center) will be included in the primary analysis model as an additional covariate. Other 
covariates may be included if considered appropriate.  
The primary analysis of the primary efficacy endpoint will be repeated as an additional 
sensitivity analysis, using the same ICE strategy as described in Section 5.8.1. This analysis will 
be based on the study population which includes all participants in the FAS who have received at 
least 80% of the doses of randomized study medication (up to the point of withdrawal or 
completion), per treatment period. Note that for participants randomized to rozanolixizumab, 
mock infusions which are given as a result of temporarily discontinuing IMP will be classified as 
a ‘missed’ dose. In addition, summary statistics of all results at assessment number 3 (in 
Treatment Periods 1 and 2) for all participants included in the model will be reported in the 
sensitivity analysis tables. 
5.8.4 
Derivations of Secondary and Exploratory Efficacy Variables 
Analyses of the following secondary efficacy endpoints will be conducted using an LMM in the 
same way as for the primary estimand analysis, using the same ICE strategies: 
• FIQR total score after 10 weeks of treatment 
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• FIQR individual domain score (activities, overall impact and symptoms) after 10 weeks of 
treatment 
• Mean 7-day pain score (NRS) after 12 weeks of treatment (collected during the 12th week). 
• Mean 7-day fatigue score (Fatigue NRS) after 12 weeks of treatment (collected during the 
12th week). 
For these endpoints, the time points to be used for analysis and baseline are as described in 
Table 5-8; the value taken at Week 11 (Visit 13) will be used as the measure of treatment effect 
for FIQR after 10 weeks of treatment for Treatment Period 1, while the FIQR assessed at Week 
23 (Visit 25) will be used as the measure of treatment effect after 10 weeks of treatment for 
Treatment Period 2. Any FIQR assessments which are not completed within the protocol defined 
window of the scheduled visit will not be included within the efficacy analysis. 
 
Note that for NRS, the participant will be asked at Visit 14 and Visit 26 to complete the pain and 
fatigue NRS assessment for that day and every day for the following 6 days, and the average of 
these 7 measurements will be taken as the endpoint. A minimum of 3 valid records among 7-day 
assessments is required to use participant’s average score.  The scores measured at Visits 7, 11, 
and the average of Visit 14 and the following 6 days for Treatment Period 1, and Visit 19, 23, 
and the average of Visit 26 and the following 6 days for Treatment Period 2 will be used within 
the LMM. 
5.9 
Other Analyses 
5.9.1 
Pressure Pain Threshold 
Pressure pain threshold will be assessed by pressure algesiometry. Pressure algesiometry will be 
performed at 2 sites on the body: (1) the lateral forearm and (2) the contralateral anterior thigh. 
Triplicate and average PPT scores by time points will be listed for all study participant at each 
time point. Mean and change from Baseline in average PPT score will be summarized by 
assessment site, treatment sequence and period, based on the FAS. If only one or two PPT 
assessments are collected at a time point, the available assessments will be used for the average 
PPT score at that time point.  
5.10 
 Biomarkers 
Venous blood samples will be collected to measure IgG binding as an exploratory endpoint.  
The reporting and analysis of the exploratory biomarker results will be conducted separately 
from the CSR and will not be covered in this SAP or associated TFL shells. 
5.11 
Immunological Endpoint  
The following blood samples for immunological testing will be collected as specified in the 
protocol schedule of activities: 
• IgA, IgE, IgM (for participants randomized under Protocol Amendments 1 and 2 only) 
• Serum complement (C3, C4) 
• Plasma complement (C3a, C5a) 
A listing of serum immunoglobulin laboratory results will be provided using the SS-r.  
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Serum and plasma complement results collected at Baseline and at any post-Baseline visits, will 
be listed using SS-r.  
5.12 
Early readout analysis and data monitoring 
5.12.1 
Early Readout Analysis 
An Early Readout Analysis is planned to be conducted after all randomized study participants 
have either completed the BPI-SF assessment at Visit 27, or have withdrawn from the study.  
For this Early Readout Analysis, a snapshot of the database will be taken once the BPI-SF data 
has been entered at Visit 27 (or earlier in the case of withdrawals) for the final randomized 
participant. The data will be cleaned for the purpose of the analysis. Details regarding the 
unblinding of individual team members and results dissemination will be provided in a separate 
unblinding plan. The study team will be unblinded following data cleaning and all study data, 
including the live random code and any vendor data previously considered unblinding will be 
provided. Some study team members will remain blinded until database lock. Details of team 
members who should remain blinded are provided in the unblinding plan. The Investigators and 
study participants will remain blind to the assigned treatment dosing regimen until the Follow-
Up Period is complete and the database is locked.  
A subset of key TFLs will be provided which will include the evaluation of the primary efficacy 
estimand, the secondary efficacy endpoints, PK and PD data, as described in Section 5.8.2, 
Section 5.8.4 , Section 5.9.1 and Section 5.5.  
5.12.2 
   Data Monitoring 
A SMC will regularly review (approximately every 3 months, with the option to adapt the 
frequency based on recruitment rates) the available blinded safety data. The first SMC review 
will be conducted approximately 2 months after randomization of the first study participant, or 
when 25% of the study participants are randomized, whatever comes first. The SMC will decide 
if the study is safe to continue. Details will be described in a separate charter. 
If there are safety concerns during the SMC session an ad hoc closed SMC meeting may be 
called if revealing treatment allocation would aid decision making. The members of closed SMC 
sessions will be restricted and specified in the charter. 
6 
CTR AND DSUR OUTPUTS 
6.1 
CTR 
The following tables outlined in previous SAP sections fulfil the criteria for transparency 
reporting for clinicaltrials.gov and EudraCT: 
• DS_T_03 Disposition and Discontinuation Reasons [RS] as per Section 5.2.1  
• DM_T_01 Demographics (all age categories are mandatory) [RS] as per Section 5.3.1  
• AE_T_01 Incidence of TEAEs – Overview (mandatory, including both All Deaths and TEAE 
leading to Deaths)] [SS-t] as per Section 5.6.2 
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• AE_T_06 Incidence of Non-Serious TEAEs Above Reporting Threshold of 5% of participants 
[SS-t] as per Section 5.6.2  
• DS_T_04 Discontinuation due to AEs [RS] as per Section 5.2.1 
• AE_T_04b Incidence of serious TEAEs by Relationship [SS-t] 
• AE_T_04b Incidence of fatal TEAEs by Relationship [SS-t] 
For results disclosure on public registries (eg. ClinicalTrials.gov), treatment-emergent adverse 
events and treatment-emergent serious adverse events will be published.  
6.2 
DSUR 
The following tables will be created by the UCB statistical programming team for reporting for 
DSUR: 
• EX_T_03 Cumulative Duration of Exposure. This table will be created for DSUR outputs 
needed whilst the study is ongoing and also once the study is completed.  
• EX_T_03 Cumulative Duration of Exposure by Treatment, Age Group and Gender. This table 
will be created once the study is completed.  
− EX_T_03 Cumulative Duration of Exposure by Treatment and Race. This table will be 
created once the study is completed.  
 
 
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7 
REFERENCES 
Cleeland, Charles S., and K. Ryan. "The brief pain inventory." Pain Research Group 20 
(1991): 143-147. 
Nehring, S.M.; Goyal, A.; Patel, B.C. (2020). StatPearls Publishing, web link: 
https://www.ncbi.nlm.nih.gov/books/NBK441843/. 
United States Department of Health and Human Services, National Cancer Institute. 
Common Terminology for Adverse Events (CTCAE), Version 5.0, November 17, 2017.  
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8 
APPENDICES  
8.1 
Appendix 1: Abnormality Criteria for Laboratory and Vital Sign 
Parameters  
8.1.1 
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. If both high and low criteria are shown 
for a parameter, the criteria should be summarized separately in tabular or graphical data 
summaries. A treatment-emergent markedly abnormal assessment is defined as any abnormal 
assessment obtained on or after the first dose of IMP in Run-In, and on or before the earliest of 
the following: the last date of infusion (including Run-Out, if applicable) +56 days, final contact 
date or death and where the corresponding Baseline value does not meet the criteria. 
 
Hematology  
PARAMETER  
UNIT 
(conventional) 
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    
Platelets  
109/L  
109/L   
<50.0 x 109/L   
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   
Bilirubin (Total)  
mg/dL  
umol/L  
>3.0 x ULN if Baseline value is normal 
(based on reference range);  
>3.0 x Baseline value if Baseline is 
abnormal   
Albumin2  
g/dL  
g/L  
<2 g/dL; <20 g/L   
Creatinine  
mg/dL  
umol/L  
>3.0 x ULN or >3.0 x |Baseline;  
Estimated glomerular 
filtrate rate (eGFR)  
mL/min/1.73 m2  mL/min/1.73 
m2  
eGFR ≤29 mL/min/1.73 m2  
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PARAMETER  
UNIT 
(conventional)  
UNIT  
(standard)  
MARKED ABNORMALITY 
CRITERIA  
C reactive protein 
(CRP)3 
mg/L  
mg/L  
>10 mg/dL; >100mg/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 G  
(g/L) 
(g/L) 
<1.09 g/L (BLQ) 
Potassium  
mmol/L  
mmol/L  
Low: <3.0 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 /dL; >10.34 mmol/L   
Triglycerides  
mg/dL  
mmol/L  
>500 mg/dL; >5.7 mmol/L  
Abbreviations: ALT= alanine aminotransferase; AST = aspartate aminotransferase; dL = deciliter; 
GGT: gamma-glutamyltransferase; L = liter; mg = milligram; mmol = millimoles; μg = microgram; 
U = unit; ULN = upper limit of normal  
Note: Marked abnormality criteria are defined by Grade 3 or higher events according to the Common 
Terminology for Adverse Events (CTCAE), Version 5.0, November 17, 2017 unless otherwise 
noted. 
1WBC (Leukocytes) markedly abnormal high criterion is not based on Version 5 CTCAE Grade 3 or higher 
criteria. Due to the allowance of concomitant steroid medication that by its mechanism of action may elevate 
WBCs, 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). 
2Albumin data is classed as unblinding and results will therefore only be available after unblinding. 
3Includes 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/.  
4Glucose high criterion defined by Grade 3 and higher events according to CTCAE, Version 4.03, June 14, 
2010. 
8.1.2 
Vital signs   
Abnormality criteria to be applied in the assessment of vital signs parameter values are given 
below. A treatment-emergent markedly abnormal assessment is defined as any abnormal 
assessment obtained on or after the first dose of IMP in Run-In, and on or before the earliest of 
the following; the last date of infusion (including Run-Out, if applicable) +56 days, final contact 
date or death and where the corresponding Baseline value does not meet the criteria. 
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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  
>38.3 0C  
Body Weight  
 ≥ 10% decrease from Baseline  
≥ 10% increase from Baseline  
  
8.2 
Appendix 2: Handling of Dates 
Partial or completely missing dates may be imputed for the following reasons: 
• Classification of AEs as TEAEs 
• Durations of AEs 
• Classification of medications and medical procedures as prior or concomitant 
• Time since diagnosis of FMS and time since first symptoms of FMS. 
Imputed dates will not be shown in the listings; all dates will be displayed as reported in the 
database. 
8.2.1 
Adverse Events 
For the classification of TEAEs, the rules below will be applied for partial or completely missing 
start dates. In general dates will be imputed conservatively such that if possible an AE will be 
classified as treatment-emergent. If a TEAE could potentially be assigned to more than one 
period, based on imputation, the following priority order will be used to impute the dates – 
Treatment Period 2>Treatment Period 1>Run-In Period:   
• If only day is missing: 
− If month and year are the same as the first dose in Treatment Period 2, then use the date 
of first dose in Treatment Period 2, else; 
− If month and year are the same as the first dose in Treatment Period 1, then use the date 
of first dose in Treatment Period 1, else; 
− If month and year are the same as the first dose in Run-In (and not the same as the first 
dose in Treatment Period 1), then use the date of first dose in Run-In. 
− If none of the above apply then use the 1st of the known month or the date of Screening if 
this is later. 
If any of the above result in an imputed start date after a known end date then use the 1st of 
the start month or the date of Screening if this is later. 
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• If day and month are missing: 
− If the year is the same as the first dose in Treatment Period 2, then use the date of first 
dose in Treatment Period 2, else; 
− If the year is the same as the first dose in Treatment Period 1, then use the date of first 
dose in Treatment Period 1, else; 
− If the year is the same as the first dose in Run-In (and not the same as the first dose in 
Treatment Period 1 or Treatment Period 2), then use the date of first dose in Run-In. 
− If none of the above apply then use the 1st of January in the known year or the date of 
Screening if this is later. 
If any of the above result in an imputed start date after a known end date then use the 1st of 
January in the known year or the date of Screening if this is later. 
• If the start date is completely unknown, then use the date of first dose in Treatment Period 2. 
If this results in an imputed start date that is after a known end date, then use 
− The date of first dose in Treatment Period 1 (if prior to known end date), else; 
− The date of first dose in Run-In (if prior to known end date), else; 
− 1st of January in the year of the end date or the date of Screening if this is later.  
Missing or partially missing dates will be imputed as described in the below table for the 
calculation of duration of each AE. Adverse event duration is computed in and reported in days.  
Calculation rules for AE duration  
Data 
availability 
Onset date Outcome 
date 
Calculation rules 
Complete data 
D1 
D2 
Duration = D2 – D1 +1 day 
Start date 
partially or 
completely 
missing 
-- 
D2 
Duration = D2 – D0 +1 day 
Notes: D0 is imputed start date per above rules. 
End date 
partially 
missing or 
completely 
missing 
D1 
-- 
For ongoing AE: 
Duration = >Discharge date – D1  
For resolved AE: 
Duration = < Discharge date – D1  
Where discharge refers to the date of the SFU/EOS 
visit, or the date of last contact if the participant did not 
attend the SFU/EOS visit. 
 
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Calculation rules for AE duration  
Data 
availability 
Onset date Outcome 
date 
Calculation rules 
Start and end 
date missing 
-- 
-- 
For ongoing AE: 
Duration = >Discharge day – D0  
For resolved AE: 
Duration = <Discharge day – D0  
Where discharge refers to the date of the SFU/EOS 
visit, or the date of last contact if the participant did not 
attend the SFU/EOS visit. 
 
Days since most recent dose/first dose in Run-In/first dose in Treatment Period 1 are calculated 
in the following way: 
AE start date – date of most recent dose/first dose of treatment in Run-In/first dose in Treatment 
Period 1 +1 day 
This calculation will only be completed for AEs with a known start date.  
 
8.2.2 
Medications 
For the classification of medications as prior or concomitant, the rules below will be applied for 
partial or completely missing start dates. In general, dates will be imputed conservatively such 
that if possible a medication will be classified as concomitant. If a medication could potentially 
be assigned to more than one period, based on imputation, the medication would be assigned to 
all possible periods.  
• If only day is missing, then use the 1st of the known month or the date of Screening if this is 
later. 
• If day and month are missing, then use the 1st of January in the known year or the date of 
Screening if this is later. 
• If the start date is completely unknown, then use the date of Screening. 
 For the classification of prior and concomitant medications  the following rules will be applied 
for partial or missing 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 participant dies, then use the date of death; 
• If the stop date is completely unknown, do not impute the stop date. 
If the stop date of a medication is completely unknown and therefore not imputed, medications 
are assumed to be concomitant in all periods following the start date, for all periods the 
participant entered.  
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8.2.3 
Procedures 
For the classification of medical procedures as prior or concomitant, the rules below will be 
applied for partial or completely missing date of procedure.  
• If only day is missing, then use the 1st of the known month or the date of Screening if this is 
later. 
• If day and month are missing, then use the 1st of January in the known year or the date of 
Screening if this is later. 
• If the date  of procedure is completely unknown, then use the date of Screening. 
8.2.4 
Time Since Diagnosis / First Symptoms of FMS 
 For the calculation of time since diagnosis of FMS and time since first symptoms of FMS, the 
following rules will be applied for partial start dates:   
• If only day is missing, then use the 1st of the known start month  
• If month and day are missing, then use January 01 in the known start year. 
If the date is completely missing, then no imputation is applied and therefore, the time since 
diagnosis / first symptoms of FMS will not be calculated.  
Time since diagnosis of FMS is calculated in the following way: 
• Time since diagnosis of FMS (years) = (date of screening – date of FMS diagnosis)/365.25 
Time since first symptoms of FMS is calculated in the following way: 
• Time since first symptoms of FMS (years) = (date of screening – date of first symptoms of 
FMS)/365.25 
Time since diagnosis and time since first symptoms will be rounded to 1 decimal place for the 
listings. 
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8.3 
Appendix 3: AEOF 
 The following events are Adverse Event of Focus for rozanolixizumab:  
  
No  
Event (also included in Title of 
TFL output)  
Selection criteria  
1  
Headache  
(Note: also included in AESM if 
severe and/or serious)  
TEAE with HLGT=’Headaches’  
2 
Possible aseptic meningitis  
SMQ=’ Noninfectious meningitis’ narrow search 
3  
Gastrointestinal disturbances  
(Note: also included in AESM if 
severe)  
TEAE with   
HLT=‘Gastrointestinal and abdominal pains (excl oral and 
throat)’ or   
HLT=‘Nausea and vomiting symptoms’ or  
HLT=‘Diarrhoea (excl infective)‘ or  
HLT=‘Gastritis (excl infective)’ or  
PT = ‘Abdominal discomfort’  
4  
Hypersensitivity reactions   
  
SMQ=’Hypersensitivity’ narrow search  
5  
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:  
  
If a participant reports any TEAE which codes to a PT 
included in Category A, then the event will be flagged as 
an anaphylactic reaction.  
  
If a participant 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 (known or imputed), then both 
events will be flagged as anaphylactic reactions.   
  
If a participant reports any TEAE which codes to a PT 
included in Category D AND reports (either a TEAE 
which codes to a PT included in Category B OR a TEAE 
which codes to a PT included in Category C), and both 
TEAEs have the same start date (known or imputed), then 
both events will be flagged as anaphylactic reactions.  
  
6  
Injection site reactions  
TEAE with  
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No  
Event (also included in Title of 
TFL output)  
Selection criteria  
HLT=’Injection site reactions’ or  
HLT=’Infusion site reactions’ or  
HLT=’Administration site reactions NEC’  
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)  
TEAEs in MedDRA SMQ = ‘Opportunistic infections’ 
narrow search  
  
9  
Effects on the kidney  
TEAEs in   
SMQ= ‘Acute renal failure’ narrow search  
10  
Drug related hepatic disorders   
TEAEs in   
SMQ=’Drug related hepatic disorders - comprehensive 
search’ narrow and broad search  
11  
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’  
  
8.4 
Appendix 4: Period of Onset Assignment 
8.4.1 
Adverse Events and IPDs 
The period of onset for AEs and IPDs is determined in the following way: 
• If the event occurs prior to the date of first dose of IMP in Run-In, then the event is assigned 
to the Screening Period. 
• Events are assigned to the Run-In Period in the following cases: 
− If the event occurs on or after the date of first dose of IMP in Run-In and prior to the date 
of first dose of IMP in Treatment Period 1. 
− If the study participant withdraws during Run-In (ie prior to the first dose of IMP in 
Treatment Period 1) and the event occurs on or after the date of first dose of IMP in Run-
In and within 6 days after the date of last dose of IMP prior to withdrawal. 
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• Events are assigned to Treatment Period 1 in the following cases: 
− If the event occurs on or after the date of first dose of IMP in Treatment Period 1 and 
prior to the date of first dose of IMP in Treatment Period 2. 
− If the study participant withdraws during Treatment Period 1 (ie prior to the first dose of 
IMP in Treatment Period 2) and the event occurs on or after the date of first dose of IMP 
in Treatment Period 1 and within 6 days after the date of last dose of IMP prior to 
withdrawal. 
• Events are assigned to Treatment Period 2 in the following cases: 
− If the event occurs on or after the date of first dose of IMP in Treatment Period 2 and 
prior to the date of first dose of IMP in Run-Out. 
− If the study participant withdraws during Treatment Period 2 (ie prior to the first dose of 
IMP in Run-Out) and the event occurs on or after the date of first dose of IMP in 
Treatment Period 2 and within 6 days after the date of last dose of IMP prior to 
withdrawal. 
• Events are assigned to the Run-Out Period in the following cases: 
− If the event occurs on or after the date of first dose of IMP in Run-Out and within 6 days 
after the date of last dose of IMP in Run-Out. 
• Events are assigned to the SFU in the following case: 
− If the event occurs on or after 7 days after the date of last dose of IMP. 
For AEs, the above rules are applied after any date imputation. 
8.4.2 
Medications  
Medications are attributed to all study periods where received, using imputed start dates, if 
required: 
• If the medication was received prior to the date of Screening, then the medication is 
attributed to the Pre-Screening Period. 
• If the medication was received on or after the date of Screening and prior to the date of first 
dose of IMP in Run-In, then the medication is attributed to the Screening Period. 
• Medications are attributed to the Run-In Period in the following cases: 
− If the medication was received on or after the date of first dose of IMP in Run-In and 
prior to the date of first dose of IMP in Treatment Period 1. 
− If the study participant withdraws during Run-In (ie prior to the date of first dose of IMP 
in Treatment Period 1) and the medication was received on or after the date of first dose 
of IMP in Run-In and within 6 days after the date of last dose of IMP prior to withdrawal. 
• Medications are attributed to Treatment Period 1 in the following cases: 
− If the medication was received on or after the date of first dose of IMP in Treatment 
Period 1 and prior to the date of first dose of IMP in Treatment Period 2. 
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− If the study participant withdraws during Treatment Period 1 (ie prior to the date of first 
dose of IMP in Treatment Period 2) and the medication was received on or after the date 
of first dose of IMP in Treatment Period 1 and within 6 days after the date of last dose of 
IMP prior to withdrawal. 
• Medications are attributed to Treatment Period 2 in the following cases: 
− If the medication was received on or after the date of first dose of IMP in Treatment 
Period 2 and prior to the date of first dose of IMP in Run-Out. 
− If the study participant withdraws during Treatment Period 2 (ie prior to the date of first 
dose of IMP in Run-Out) and the medication was received on or after the date of first 
dose of IMP in Treatment Period 2 and within 6 days after the date of last dose of IMP 
prior to withdrawal. 
• Medications are attributed to the Run-Out Period in the following cases: 
− If the medication was received on or after the date of first dose of IMP in Run-Out and 
within 6 days after the date of last dose of IMP in Run-Out. 
• Medications are attributed to the SFU in the following case: 
− If the medication was received on or after 7 days after the date of last dose of IMP. 
 
9 
AMENDMENT(S) TO THE STATISTICIAL ANALYSIS PLAN 
(SAP) 
9.1 
Amendment 1 
The following updates were made in SAP Amendment 1: 
• The exploratory endpoints listed in Section 1.1 were updated to align with Protocol 
Amendment 3 
• Section 1.2 was updated to include the inclusion criteria for study participants enrolled under 
all versions of the protocol.  
• Clarifications were made to the definitions of the SS-t and PDS in Section 4 
• The definition of Period Day was updated in Section 5.1.1.1 and clarification of study 
periods was added to Section 5.1.1.2. 
• The definitions of Baseline were updated for hematology, serum chemistry, urinalysis, vital 
signs and ADA assessments in Section 5.1.1.3. The ECG endpoint was removed, and the PD 
and Pressure Pain Threshold Baseline definitions were added to the table. 
• Duplicated text relating to the analysis sets was removed from Section 5.1.1.4 
• An additional sub-section (Section 5.1.2) was added detailing the changes to protocol-
defined-analyses  
• Clarification relating to the reporting of IPDs and details regarding the classification of IPDs 
and analysis sets for the early readout and final analysis were added to Section 5.1.3.  
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• Clarification of the handling of early withdrawal events was added to Section 5.1.5. 
• The WHO-DD version was updated throughout 
• The calculation of total days on study medication was added to Section 5.2.1 and clarification 
of how the period of discontinuation is to be derived was added. 
• Section 5.3.1 was updated to include weight and BMI categories to the list of required 
categorical demographic summaries.  
• Additional sections were added to denote the listing requirements for the History of 
Headache and Medical History on Pain Management Programs eCRF following Protocol 
Amendment 3. 
• The definitions of prior and concomitant medications were amended in Section 5.3.6 and 
clarification was added regarding the attribution of medications to study periods. Reference 
to prior and concomitant medical procedures was removed and a new section was added for 
the definition and listing requirements of medical procedures (Section 5.3.7).  
• Clarification of the TFL requirements for the pharmacokinetics and pharmacodynamics 
endpoints were added to Sections 5.5.1 and 5.5.2, respectively.  
• Section 5.6.1 was updated to ensure the TFL summaries for extent of exposure cover all 
planned treatment sequences and not exposure to active drug only. In addition, the derivation 
of study medication duration was split out into 2 calculations for the summaries, and the 
summary by treatment duration category was removed. 
• In Section 5.6.2, the definition of TEAE was amended. The requirements of the table 
summaries were clarified, the requirement of exposure adjusted analysis was removed, and 
the data required in the AE listings was clarified.  In addition, the summaries of drug-related 
TEAEs and serious drug-related TEAEs by preferred term were added. 
• The definition of treatment-emergent was updated in Section 5.6.6 and Appendix 1. 
• The requirements of the clinical laboratory tables and listings were updated in Section 5.6.6 
• The requirements of the time points to summarise for the vital signs tables were updated in 
Section 5.6.7 
• ECG assessments at Visit 15, 27, and EOT/EW were removed from the schedule of 
assessments in Protocol Amendment 3. Therefore, the description of the summary tables 
were removed from Section 5.6.8. 
• The requirements of the immunogenicity analysis were re-defined in Section 5.7. 
• Section 5.8 was updated to clarify the table summary requirements of the efficacy endpoints, 
as well as the Forest plot requirements, and to clarify how multiple daily pain and fatigue 
NRS scores should be handled. 
• The model to be used for the secondary analysis was updated to align with the model for the 
primary efficacy analysis in Section 5.8.2.2 
• Section 5.8.3 was updated to clarify the requirements of the supportive and sensitivity 
analyses.  
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• Clarifications of the secondary and exploratory efficacy endpoints were added to Section 
5.8.4  
• Clarification that no imputation of efficacy variables will be conducted was added to Section 
5.8.5 
• The analysis requirements of the immunological endpoints were updated in Section 5.11 
• Reference to the Interim Analysis was removed throughout. 
• Section 5.12.1 was updated with a description of the Early Readout Analysis. 
• Section 6.2 was updated to clarify that the DSUR tables will be completed by the UCB 
statistical programming team. 
• Appendix 1 and 2 (Schedule of Activities and Changes to Protocol Planned Analyses) were 
removed and subsequent appendices were re-numbered accordingly.  
• Minor amendments were made to the TEMA criteria for WBC, glucose and IgG laboratory 
assessments marked abnormality criteria in Section 7.1 
• Section 7.2 was updated to add reference to partial times when classifying TEAEs and prior 
and concomitant medications, and calculating AE durations and time to onset of AEs. Rules 
were also added for handling partial dates of medical procedures and diagnosis and first 
symptoms of FMS. 
• Section 7.3 was updated to align with the AEOF criteria listed in the FM0001 PSAP. 
• Section 7.4 was added to clarify the assignment of period of onset for AEs, IPDs, and 
medications  
Additional minor clarifications and cosmetic updates were made throughout. 
 
 
 
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Approval Signatures
Name:
FM0001-sap-amend-1
Version:
1. 0
Document Number:
CLIN-000224266
Title:
FM0001-sap-amend-1
Approved Date:
16 May 2024
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Qualified Person
Date of Signature: 10-May-2024 09:37:27 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 16-May-2024 09:08:16 GMT+0000
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