Clinical trial NCT05514873
Conditions: Generalized Myasthenia Gravis
Keywords: gMG
Sponsor: UCB Biopharma SRL
Start date: 2022-10-31; Completion date: 2024-10-23
Enrollment: 26 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the study is to evaluate the safety and tolerability of switching from intravenous (IV) complement component 5 (C5) inhibitors to subcutaneous (SC) Zilucoplan in study participants with generalized myasthenia gravis (gMG)

Detailed description:

Arms: arm 1: Study participants will be treated with subcutaneous zilucoplan (0.3mg/kg/day)
Interventions: intervention 1: zilucoplan (RA101495)
Intervention descriptions: intervention 1: Subcutaneous injection

Protocol documents:
Prot_000.pdf: 
UCB 
 
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A PHASE 3B, MULTICENTER, OPEN-LABEL, SINGLE-ARM 
STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND 
EFFICACY OF ZILUCOPLAN IN PARTICIPANTS WITH 
GENERALIZED MYASTHENIA GRAVIS SWITCHING FROM 
INTRAVENOUS COMPLEMENT COMPONENT 5 INHIBITORS 
TO SUBCUTANEOUS ZILUCOPLAN 
 
PROTOCOL MG0017 
PHASE 3b 
 
SHORT TITLE: 
An open-label study to evaluate the safety, tolerability, and efficacy of subcutaneous zilucoplan 
in participants with generalized myasthenia gravis who were previously receiving intravenous 
complement component 5 inhibitors 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying number: 
IND Number: 
134340  
Confidential Material 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document History 
Document 
Date 
Type of amendment 
Amendment 3 
30 Nov 2022 
Not applicable 
Amendment 2 
21 Oct 2022 
Not applicable 
Amendment 1 
15 Jul 2022 
Not applicable 
Original Protocol 
24 May 2022 
Not applicable 
 
Amendment 3 (30 Nov 2022) 
Overall Rationale for the Amendment: 
The protocol amendment introduces an optional Extension Treatment Period that allows access 
to zilucoplan for participants who wish to continue receiving it after completing the 12-week 
Main Treatment Period of the study. It allows for study participants to continue receiving 
zilucoplan treatment until the approval of the marketing application for the indication of 
generalized myasthenia gravis (gMG) in the US or until further notice from the Sponsor.  
The table below does not include correction of minor typographical errors and 
formatting/stylistic changes. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1, Synopsis 
Section 3, Table 3-1 
Objectives and 
estimands/endpoints 
Section 4.1, Overall design 
Section 4.2, Scientific 
rationale for study design 
Section 4.4, End of study 
definition 
Section 6.1, Treatments 
administered 
Section 6.8, Treatment after 
the end of the study 
Section 7.1.2, QTc stopping 
criteria 
Section 8.1.1.6, Patient 
Preference assessment 
Section 8.1.1.8, Time to 
first receipt of rescue 
therapy 
Endpoints updated to define the 
duration. Overall design of the study, 
treatment groups and duration updated 
to include the Extension Treatment 
Period. 
To include an Extension 
Treatment Period in the study 
and allow eligible 
participants who have 
completed the 12-week Main 
Treatment Period to have 
continued access to 
zilucoplan. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.1.1.9, Change in 
SOC therapy dose regimen 
Section 1.2, Schema 
Figure 1-1 updated to include the 
Extension Treatment Period. 
Footnotes “d,” “e,” "f," "g," and "h" 
added. 
Footnote “b” modified for clarity 
reasons. 
As above. 
Section 1.3, Schedule of 
Activities 
Table 1-2 updated to include the 
Extension Treatment Period and time 
points for data collection. 
Footnote “b,” “c,” “k,” and “u” 
updated. 
Footnote “w” and “x” added. 
As above. 
 
 
Footnotes “k” and “u” 
modified for clarity reason. 
 
Section 2.3, Benefit/risk 
assessment 
Reference to Advisory Committee on 
Immunization Practices added. 
Clarification. 
Section 5.1, Inclusion 
criteria 
Inclusion Criterion 2 (now 2a) modified 
for clarity reason. 
Clarification. 
Inclusion Criteria 7, 8, and 10 (now 7a, 
8a, and 10a, respectively) modified. 
Modified to account for the 
Main Treatment Period and 
clarification added on the 
entire study. 
Reference to Advisory Committee on 
Immunization Practices added to 
exclusion criterion 9 (now 9a). 
Clarification. 
Section 5.2, Exclusion 
criteria 
Exclusion Criteria 3, 12, 14 (now 3a, 
12a, and 14a, respectively) modified.  
Modified to account for the 
Main Treatment Period 
and/or Extension Treatment 
Period. 
Section 6, Study Treatments 
Second paragraph modified. 
Modified to account for the 
Main Treatment Period and 
the Extension Treatment 
Period for more clarity. 
Section 6.5.1, Permitted 
concomitant treatments 
(medications and therapies) 
Modified due to addition of Extension 
Treatment Period to the study. 
Modified to account for the 
Main Treatment Period and 
Extension Treatment Period. 
Section 6.5.2, Prohibited 
concomitant treatments 
(medications and therapies) 
The last paragraph modified. 
Updated due to the addition 
of the Extension Treatment 
Period to the study. 
Section 6.5.3, Vaccines 
Reference to Advisory Committee on 
Immunization Practices added. 
Clarification made that 
withdrawal of participants 
due to prohibited 
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Section # and Name 
Description of Change 
Brief Rationale 
concomitant medication not 
necessary (except for IV C5 
inhibitors). 
Section 6.5.4, Rescue 
medication 
Last paragraph changed. 
Clarification. 
Section 7.1, Discontinuation 
of study medication 
Paragraph updated. 
Clarification. 
Section 7.2, Participant 
discontinuation/withdrawal 
from the study 
Criterion 3 updated with general 
prohibited concomitant medication 
being replaced with IV C5 inhibitors.  
 Clarification. 
Sentence on Early Withdrawal and 
Withdrawal Visits modified. 
Updated due to the addition 
of the Extension Treatment 
Period. 
Section 8.3.1, Time period 
and frequency for collecting 
AE and SAE information 
Sentence shortened. 
Deleted information on the 
Withdrawal and Safety 
Follow-Up Visits as this is 
already given the cross-
referenced Section 4.4. 
Section 8.3.5, Pregnancy 
Withdrawal Visit included. 
Updated in line with 
modifications made in Table 
1-2. 
Section 8.4, Safety signal 
detection 
“(eg, AEs, vital signs, laboratory, or 
ECG results)” deleted. 
Updated, since in the 
Extension Treatment Period 
only a subset of safety 
variables mentioned in the 
deleted parentheses will be 
collected.  
Section 9.7, Planned interim 
analysis and data 
monitoring 
Interim analysis was added. 
Updated due to the addition 
of the Extension Treatment 
Period. 
Section 10.4, Appendix 4, 
Contraceptive guidance and 
collection of pregnancy 
information 
Contraception guidance updated to 
include the whole study rather than just 
the Main Treatment Period. 
As above. 
 
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SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h) 
Fax 
US and Canada: +1 800 880 6949 or +1 866 890 3175 
Email 
Global: DS_ICT@ucb.com (for interventional clinical studies) 
 
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TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ............................................................................................... 10 
1.1 
Synopsis ....................................................................................................................... 10 
1.2 
Schema ......................................................................................................................... 15 
1.3 
Schedule of Activities .................................................................................................. 17 
2 
INTRODUCTION ........................................................................................................... 24 
2.1 
Study rationale ............................................................................................................. 24 
2.2 
Background .................................................................................................................. 24 
2.3 
Benefit/risk assessment ................................................................................................ 25 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 26 
3.1 
Estimand/intercurrent event handling rationale and impact on the study .................... 28 
4 
STUDY DESIGN ............................................................................................................. 29 
4.1 
Overall design .............................................................................................................. 29 
4.2 
Scientific rationale for study design ............................................................................ 31 
4.3 
Justification for dose .................................................................................................... 31 
4.4 
End of study definition................................................................................................. 32 
5 
STUDY POPULATION .................................................................................................. 33 
5.1 
Inclusion criteria .......................................................................................................... 33 
5.2 
Exclusion criteria ......................................................................................................... 34 
5.3 
Lifestyle restrictions..................................................................................................... 36 
5.4 
Screen failures .............................................................................................................. 36 
6 
STUDY TREATMENTS ................................................................................................. 36 
6.1 
Treatments administered .............................................................................................. 36 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 38 
6.2.1 
Drug accountability ............................................................................................. 38 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 38 
6.4 
Treatment compliance .................................................................................................. 39 
6.5 
Concomitant medication(s)/treatment(s) ..................................................................... 39 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 39 
6.5.2 
Prohibited concomitant treatments (medications and therapies) ......................... 39 
6.5.3 
Vaccines ............................................................................................................... 40 
6.5.4 
Rescue medication ............................................................................................... 40 
6.6 
Dose modification ........................................................................................................ 41 
6.7 
Criteria for study hold or dosing stoppage ................................................................... 41 
6.8 
Treatment after the end of the study ............................................................................ 41 
7 
DISCONTINUATION OF STUDY MEDICATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 42 
7.1 
Discontinuation of study medication ........................................................................... 42 
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7.1.1 
Liver chemistry stopping criteria ......................................................................... 42 
7.1.2 
QTc stopping criteria ........................................................................................... 43 
7.2 
Participant discontinuation/withdrawal from the study ............................................... 44 
7.3 
Lost to follow up .......................................................................................................... 45 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 45 
8.1 
Efficacy assessments .................................................................................................... 46 
8.1.1 
Clinical efficacy assessments .............................................................................. 46 
8.1.1.1 
MG-ADL ................................................................................................... 46 
8.1.1.2 
QMG scale ................................................................................................. 47 
8.1.1.3 
MG-QOL15r .............................................................................................. 47 
8.1.1.4 
Myasthenia Gravis Foundation of America Post-Intervention Status ....... 47 
8.1.1.5 
TSQM-9 ..................................................................................................... 47 
8.1.1.6 
Patient Preference assessment ................................................................... 47 
8.1.1.7 
Time needed for administration of SC ZLP .............................................. 48 
8.1.1.8 
Time to first receipt of rescue therapy ....................................................... 48 
8.1.1.9 
Change in SOC therapy dose regimen ...................................................... 48 
8.1.2 
Pharmacodynamics .............................................................................................. 48 
8.2 
Safety assessments ....................................................................................................... 48 
8.2.1 
Physical examination ........................................................................................... 49 
8.2.2 
Vital signs ............................................................................................................ 49 
8.2.3 
Electrocardiogram ................................................................................................ 49 
8.2.4 
Clinical safety laboratory assessments ................................................................ 49 
8.2.5 
Suicidal risk monitoring ...................................................................................... 50 
8.3 
AEs and SAEs .............................................................................................................. 50 
8.3.1 
Time period and frequency for collecting AE and SAE information .................. 50 
8.3.2 
Method of detecting AEs and SAEs .................................................................... 51 
8.3.3 
Follow-up of AEs and SAEs ................................................................................ 51 
8.3.4 
Regulatory reporting requirements for SAEs ...................................................... 51 
8.3.5 
Pregnancy ............................................................................................................ 51 
8.3.6 
Adverse events of special interest ........................................................................ 52 
8.3.7 
Monitoring of infection ........................................................................................ 52 
8.4 
Safety signal detection ................................................................................................. 52 
8.5 
Treatment of overdose ................................................................................................. 52 
8.6 
Pharmacokinetics ......................................................................................................... 53 
8.7 
Immunogenicity assessments ....................................................................................... 53 
8.8 
Health economics ......................................................................................................... 54 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 54 
9.1 
Definition of analysis sets ............................................................................................ 54 
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9.2 
General statistical considerations ................................................................................. 54 
9.3 
Planned efficacy/outcome analyses ............................................................................. 55 
9.3.1 
Secondary efficacy estimand/secondary endpoint analyses ................................ 55 
9.3.2 
Other efficacy endpoint analyses ......................................................................... 55 
9.4 
Planned safety and other analyses................................................................................ 55 
9.4.1 
Safety analyses ..................................................................................................... 55 
9.4.2 
Other analyses ...................................................................................................... 55 
9.5 
Handling of protocol deviations................................................................................... 55 
9.6 
Handling of dropouts or missing data .......................................................................... 56 
9.7 
Planned interim analysis and data monitoring ............................................................. 56 
9.8 
Determination of sample size ....................................................................................... 56 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 57 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ......................... 57 
10.1.1 
Regulatory and ethical considerations ................................................................. 57 
10.1.2 
Financial disclosure ............................................................................................. 57 
10.1.3 
Informed consent process .................................................................................... 58 
10.1.4 
Data protection ..................................................................................................... 58 
10.1.5 
Committees structure ........................................................................................... 59 
10.1.6 
Data quality assurance ......................................................................................... 59 
10.1.6.1 
Case report form completion ..................................................................... 59 
10.1.6.2 
Apps ........................................................................................................... 59 
10.1.7 
Source documents ................................................................................................ 60 
10.1.8 
Study and site closure .......................................................................................... 60 
10.1.9 
Publication policy ................................................................................................ 60 
10.2 
Appendix 2: Clinical laboratory tests .......................................................................... 62 
10.3 
Appendix 3: Adverse events – Definitions and procedures for recording, evaluating, 
follow up, and reporting ............................................................................................... 64 
10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ......... 70 
10.5 
Appendix 5: Genetics ................................................................................................... 73 
10.6 
Appendix 6: Liver safety – suggested actions and follow-up assessments ................. 74 
10.7 
Appendix 7: Medical device AEs, adverse device effects, SAEs, and device 
deficiencies: Definition and procedures for recording, evaluating, follow-up, and 
reporting ....................................................................................................................... 78 
10.8 
Appendix 8: Rapid alert procedures ............................................................................ 79 
10.9 
Appendix 9: Country-specific requirements ................................................................ 80 
10.10 Appendix 10: Abbreviations and trademarks .............................................................. 81 
10.11 Appendix 11: Protocol amendment history ................................................................. 83 
Amendment 1 (15 Jul 2022) .................................................................................................... 83 
Amendment 2 (21 Oct 2022) ................................................................................................... 87 
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11 REFERENCES ................................................................................................................ 88 
SPONSOR DECLARATION .................................................................................................. 90 
 
LIST OF TABLES 
Table 1‒1: 
Objectives and estimands/endpoints ................................................................ 10 
Table 1‒2: 
Schedule of Activities ...................................................................................... 17 
Table 3‒1: 
Objectives and estimands/endpoints ................................................................ 26 
Table 6‒1: 
Treatment administered ................................................................................... 37 
Table 6‒2: 
ZLP dose presentations by weight brackets ..................................................... 37 
Table 10‒1: 
Protocol-required safety laboratory assessments ............................................. 62 
Table 10‒2: 
Highly effective contraceptive methodsa ......................................................... 71 
Table 10‒3: 
Liver chemistry stopping criteria and follow-up assessments ......................... 74 
Table 10‒4: 
Liver chemistry increased monitoring criteria with continued study 
medication ........................................................................................................ 76 
 
LIST OF FIGURES 
Figure 1‒1: 
MG0017 study schematic ................................................................................ 15 
Figure 7‒1: 
Liver chemistry stopping criteria and increased monitoring algorithm ........... 42 
Figure 7‒2: 
Liver chemistry increased monitoring algorithm with continued study 
intervention for participants with ALT 3xULN but <8xULN ....................... 43 
 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title: A Phase 3b, multicenter, open-label, single-arm study to evaluate the safety, 
tolerability, and efficacy of zilucoplan in participants with generalized myasthenia gravis 
switching from intravenous complement component 5 inhibitors to subcutaneous zilucoplan 
Short title: An open-label study to evaluate the safety, tolerability, and efficacy of subcutaneous 
zilucoplan in participants with generalized myasthenia gravis who were previously receiving 
intravenous complement component 5 inhibitors 
Rationale: 
Myasthenia gravis (MG) is a serious, sometimes life-threatening, debilitating condition 
associated with numerous symptoms including muscular weakness and fatigue. There remains a 
need for safe and effective treatments to conveniently treat patients with MG, including 
generalized myasthenia gravis (gMG), where the disease progresses beyond the ocular muscles 
and affects multiple muscle groups throughout the body. Some patients can manage their 
symptoms with oral medications such as an oral acetylcholinesterase inhibitors, corticosteroids, 
or nonsteroidal immunosuppressants. In addition, intravenous immunoglobulin G and plasma 
exchange treatment could be utilized as well. For those whose symptoms are not well managed 
by these medications, a potential alternative is long term treatment with approved intravenous 
(IV) complement component 5 (C5) inhibitors (eg, eculizumab or ravulizumab) which have 
proven effective at treating MG symptoms. However, there remains a need for new therapeutic 
options available to patients for whom IV infusions represent a high administration burden, have 
difficult venous access, or who are in underserved or rural populations where economic access to 
IV infusions is prohibitive. MG0017 aims to evaluate the disease control and safety and 
tolerability after switching from an approved IV C5 inhibitor to subcutaneous (SC) zilucoplan 
(ZLP), as well as the evaluation of patient satisfaction and preference. 
Objectives and endpoints 
Table 1‒1: 
Objectives and estimands/endpoints 
Objectives 
Estimands/endpoints 
Primary 
To evaluate the safety and 
tolerability of switching from IV 
C5 inhibitors to SC ZLP in study 
participants with gMG 
The primary safety endpoints are: 
• 
Incidence of TEAEs over the Main Treatment Period 
• 
Incidence of TEAEs leading to withdrawal of study medication 
over the Main Treatment Period 
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Table 1‒1: 
Objectives and estimands/endpoints 
Objectives 
Estimands/endpoints 
Secondary 
To evaluate the efficacy of SC 
ZLP after switching from IV C5 
inhibitors in study participants 
with gMG 
The secondary efficacy estimand is: 
• 
Treatment: ZLP administered by daily SC injections 
(0.3mg/kg/day) 
• 
Target population: Adult study participants with gMG currently 
receiving an IV C5 inhibitor approved for the treatment of 
gMG according to the protocol-specified inclusion/exclusion 
criteria 
• 
Endpoint: CFB to Week 12 in MG-ADL score 
• 
Intercurrent event handling: The intercurrent events considered 
in this study are: 
− 
Administration of rescue therapy or changes in SOC dose 
regimens. Data collected at and after the point of the 
intercurrent event will be used as collected to gain 
understanding of clinical practice. 
− 
Participant discontinuation from the study. It will be 
assumed that the participant had remained on their 
treatment (regardless of rescue therapy administration) 
throughout the study (ie, a "hypothetical strategy" 
assuming participants did not discontinue the study and 
remained on treatment). 
• 
Population level summary: The mean of the endpoint 
To evaluate the efficacy of SC 
ZLP after switching from IV C5 
inhibitors on an additional 
efficacy endpoint in study 
participants with gMG 
The secondary efficacy endpoint is: 
• 
CFB to Week 12 in the QMG score 
This endpoint will be analyzed following the same estimand 
structure as defined for the MG-ADL score. The endpoint assessed 
will change accordingly. 
To evaluate safety and 
tolerability of SC ZLP after 
switching from IV C5 inhibitors 
on additional safety measures in 
study participants with gMG 
The secondary safety endpoints are: 
• 
Incidence of serious TEAEs over the Main Treatment Period 
• 
Incidence of study withdrawal over the Main Treatment Period 
Other 
To further explore the efficacy of 
SC ZLP on additional efficacy 
endpoints after switching from 
IV C5 inhibitors in study 
participants with gMG 
The other efficacy endpoints are: 
• 
Time to first receipt of rescue therapy over the Main Treatment 
Period 
• 
Change in SOC therapy medication dose regimen for gMG 
during the Main Treatment Period 
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Table 1‒1: 
Objectives and estimands/endpoints 
Objectives 
Estimands/endpoints 
• 
Achievement of Minimal Manifestation Status per MGFA-PIS 
at Week 12 without rescue therapy 
• 
Achieving MSE, defined as an MG-ADL of 0 or 1 at Week 12 
without rescue therapy 
• 
CFB to Week 12 in QMG subscores: ocular, bulbar, 
respiratory, limb 
• 
CFB to Week 12 in MG-QOL15r score 
• 
MG-ADL score responder rate (responder is defined as 
achieving ≥3-point improvement from Baseline [decrease] at 
Week 12 and not having taken rescue therapy) 
• 
QMG score responder rate (responder is defined as achieving  
≥5-point improvement from Baseline [decrease] at Week 12 
and not having taken rescue therapy) 
To explore the time needed for 
administration of SC ZLP 
The other endpoint is: 
• 
Time needed for administration of SC ZLP 
To explore study participants’ 
treatment satisfaction following 
the use of SC ZLP 
The other endpoint is: 
• 
CFB to Week 12 in TSQM-9 scores 
To explore study participant 
preference following the use of 
SC ZLP 
The other endpoint is: 
• 
Patient Preference assessment at Week 12 
To further evaluate the safety 
and tolerability of SC ZLP after 
switching from IV C5 inhibitors 
on other safety measures in 
study participants with gMG 
The other safety endpoints are: 
• 
CFBa to Week 12 in clinical laboratory tests 
• 
CFBa to Week 12 in physical examination 
• 
ECGa 
• 
C-SSRS 
• 
Incidence of TEAEs 
To evaluate the PK of SC ZLP 
after switching from IV C5 
inhibitors 
The other PK endpoint is: 
• 
Plasma concentrations of ZLP and its major metabolites over 
the Main Treatment Period 
 
To evaluate the PD of SC ZLP 
after switching from IV C5 
inhibitors 
The other PD endpoint is: 
• 
sRBC lysis assay for evaluation of classical complement 
pathway activation over the Main Treatment Period 
a In this study, the clinical laboratory, physical examination, and ECG assessments conducted at Screening will be 
considered the baseline values for evaluating of the other safety endpoints. 
C5=complement component 5; CFB=change from Baseline; C-SSRS=Columbia-Suicide Severity Rating Scale; 
ECG=electrocardiogram; gMG=generalized myasthenia gravis; IV=intravenous; MG-ADL=Myasthenia 
Gravis-Activities of Daily Living; MG-QOL15r=Myasthenia Gravis – Quality of Life revised; 
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Table 1‒1: 
Objectives and estimands/endpoints 
Objectives 
Estimands/endpoints 
MGFA-PIS=Myasthenia Gravis Foundation of America Post-Intervention Status; MSE=Minimal Symptom 
Expression; PD=pharmacodynamic(s); PK=pharmacokinetic(s); QMG= Quantitative Myasthenia Gravis; 
SC=subcutaneous; SOC=standard of care; sRBC=sheep red blood cell; TEAE=treatment-emergent adverse 
event; TSQM-9=9-item Treatment Satisfaction Questionnaire for Medication; ZLP=zilucoplan 
Overall design 
MG0017 is a Phase 3b, multicenter, open-label, single-arm study to evaluate the safety, 
tolerability, and efficacy of ZLP in adult study participants (≥18 years of age) with gMG 
switching from their current IV C5 inhibitor to SC ZLP. 
To be eligible to participate in this study, participants must be currently receiving an IV C5 
inhibitor approved for the treatment of gMG for at least 3 months (for eculizumab) or 4 months 
(for ravulizumab) prior to Screening (with the last dose being administered at the Screening Visit 
±3 days), considered to have a clinically stable disease as per the Investigator’s judgment prior to 
Screening, and willing to switch from their current IV C5 inhibitor to SC ZLP. 
The study includes a 2-week or 8-week Screening Period (for participants receiving eculizumab 
or ravulizumab, respectively), a 12-week Main Treatment Period, and an optional Extension 
Treatment Period. A Safety Follow-up (SFU) Visit should be performed 40 days (±7 days) after 
the last dose of study medication. 
The Screening Visit should be scheduled to coincide with the regularly scheduled study 
participant’s IV C5 inhibitor administration (±3 days). Up to and including the time of the 
Screening Visit, study participants will continue to receive their IV C5 inhibitor at the 
recommended dose regimen. 
On Day 1, study participants will receive ZLP 0.3mg/kg administered SC. Following in-clinic 
education and training, all study participants will self-inject daily SC doses of study medication 
for the subsequent 12 weeks. Of note, there will be no washout period during the study where 
study participants are not receiving treatment for MG. 
During the Main Treatment Period, study participants will be contacted via phone call at Week 1, 
Week 4, and Week 8 to assess safety and tolerability. During these phone call visits, the 
Myasthenia Gravis-Activities of Daily Living (MG-ADL) assessment will also be performed. 
Study participants will return to the clinic at Week 2 and Week 12 to evaluate safety, tolerability, 
and efficacy. Additional assessments will include questionnaires, pharmacokinetics (PK), and 
pharmacodynamics (PD). 
All study participants who complete the 12-week Main Treatment Period without discontinuing 
study medication will have the option to continue ZLP treatment in the Extension Treatment 
Period after the Week 12 visit. Participants who withdraw during the Main Treatment Period will 
complete an Early Withdrawal (EW) Visit followed by a SFU Visit 40 days (±7 days) after the 
last dose of study medication. Participants who opt not to continue into the Extension Treatment 
Period will complete a SFU Visit 40 days (±7 days) after the last dose of study medication. 
The Extension Treatment Period consists of in-clinic visits every 12 weeks (±7 days) and will 
continue until all participants are withdrawn, until ZLP is approved and available in the US, or 
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until further notice from the Sponsor. During these visits, ZLP accountability and resupply will 
be performed, medications updated, and safety will be assessed. Participants who withdraw or 
discontinue ZLP during the Extension Treatment Period will complete a Withdrawal Visit 
followed by a SFU Visit 40 days (±7 days) after the last dose of study medication. Participants 
who transition to commercially available ZLP will complete a Withdrawal Visit but will not 
require a SFU Visit. If by the time a participant completes the Main Treatment Period ZLP is 
commercially available, the participant may transition to commercially available ZLP directly 
following the Week 12 visit at the end of the Main Treatment Period. 
Number of participants 
Twenty study participants are planned to be enrolled in the study. 
Treatment groups and duration 
Study participants will be treated with SC ZLP (0.3mg/kg/day). 
The duration of the study depends on the participant’s decision to continue into the Extension 
Treatment Period and on the commercial availability of ZLP in the US (or until further notice 
from the Sponsor). 
The total duration of the study per participant completing the Main Treatment Period and not 
continuing into the Extension Treatment Period will be approximately 20 to 26 weeks: 
• 2-week Screening Period for study participants receiving eculizumab or an 8-week Screening 
Period for study participants receiving ravulizumab 
• 12-week Main Treatment Period 
• An SFU Visit 40 days (±7 days) after the last dose of study medication.
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1.2 
Schema 
A schematic of the study design is provided in Figure 1‒1. 
Figure 1‒1: MG0017 study schematic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BL=Baseline; C5=complement component 5; EW=Early Withdrawal; IV=intravenous; MG-ADL=Myasthenia Gravis-Activities of Daily Living; 
SC=subcutaneous; SFU=Safety Follow-up; ZLP=zilucoplan 
a The Screening Visit should be scheduled to coincide with the regularly scheduled study participant IV C5 inhibitor administration (±3 days). 
b Up to and including the time of the Screening Visit, study participants will continue to receive their IV C5 inhibitor at the recommended dose regimen. The last 
regularly scheduled IV C5 inhibitor administration must occur at the Screening Visit (±3 days) to ensure approximately a 2-week (eculizumab) or 8-week 
(ravulizumab) interval between the last regularly scheduled IV C5 inhibitor administration and the first SC ZLP administration at the Baseline Visit, 
respectively. 
c At Day 1 of the Main Treatment Period (BL) in case of no more than a 2-point change in study participants’ MG-ADL score compared to the Screening Visit 
(±3 days), study participants will switch to SC ZLP (0.3mg/kg/day). 
Screening Period
a 
(2-week or 8-week) 
Daily SC ZLP  
until Week 12  
IV C5 inhibitor
b 
Daily SC ZLP  
after Week 12 f 
Transition to 
commercially available 
Zilucoplan g, h 
(if/when approved in the 
US) 
BL Visit 
Switch, Day 1
c 
Week 12 Visit 
SFU d 
SFU 
Main Treatment Period e 
Extension Treatment Period 
h 
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d For participants who complete the Main Treatment Period but decide not to continue into the Extension Treatment Period: An SFU Visit will be performed 
40 days (±7 days) after the last dose of study medication. 
e If a study participant permanently withdraws from the study prior to the Week 12 visit, an EW Visit will be performed. 
f For study participants continuing into the Extension Treatment Period, SC ZLP will be provided after completion of the Main Treatment Period until they 
discontinue ZLP, or are able to receive commercial ZLP (if/when available in the US), or until further notice from the Sponsor. For participants who 
discontinue ZLP during the Extension Treatment Period, a Withdrawal Visit and a SFU Visit will be conducted 40 days (±7 days) after the last dose of study 
medication. 
g Participants who transition to commercially available ZLP (if/when approved in the US) will complete a Withdrawal Visit but will not require a SFU Visit.  
h If ZLP is commercially available by the time a participant completes the Main Treatment Period, the participant may transition to commercially available ZLP 
directly following the Week 12 visit at the end of the Main Treatment Period. 
 
 
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1.3 
Schedule of Activities 
The schedule of study activities is provided in Table 1‒2. 
Table 1‒2: 
Schedule of Activities 
Study Period 
Screening 
Perioda 
Main Treatment Period 
Extension 
Treatment 
Period 
EW/ 
With-
drawal 
Visitb,w 
(In-
clinic) 
SFU 
Visit 
(In-
clinic)c 
Rescue 
Therapy 
Visit (If 
applicable
)d 
Visit name 
Screening 
Visit 
(In-clinic) 
Baselinee 
(In-clinic) 
Week 1 
(Phone 
call) 
Week 
2 (In-
clinic) 
Week 
4 
(Phone 
call) 
Week 
8 
(Phone 
call) 
Week 
12 (In-
clinic) 
Week 24, 
36, 48… 
every 12 
weeks 
(In-clinic) 
Visit # 
1 
2 
3 
4 
5 
6 
7 
8, 9, 10… 
– 
– 
– 
Day 
-14 or -56 
1 
8 
15 
29 
57 
84 
168, 252, 
336… 
 
(Last 
dose 
+40 
days) 
 
Visit Windowf 
±3d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
 
±7d 
 
Procedure/activity 
Informed consentg 
X 
 
 
 
 
 
 
 
 
 
 
Verification of 
inclusion/exclusion criteriag 
X 
X 
 
 
 
 
 
 
 
 
 
Study participant safety card 
issued 
 
X 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Medical/surgical historyh 
X 
 
 
 
 
 
 
 
 
 
 
Reason for switch from IV C5 
inhibitor 
X 
 
 
 
 
 
 
 
 
 
 
Height and weighti 
X 
 
 
 
 
 
X 
X 
X 
 
 
Prior and concomitant 
medicationsj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Table 1‒2: 
Schedule of Activities 
Study Period 
Screening 
Perioda 
Main Treatment Period 
Extension 
Treatment 
Period 
EW/ 
With-
drawal 
Visitb,w 
(In-
clinic) 
SFU 
Visit 
(In-
clinic)c 
Rescue 
Therapy 
Visit (If 
applicable
)d 
Visit name 
Screening 
Visit 
(In-clinic) 
Baselinee 
(In-clinic) 
Week 1 
(Phone 
call) 
Week 
2 (In-
clinic) 
Week 
4 
(Phone 
call) 
Week 
8 
(Phone 
call) 
Week 
12 (In-
clinic) 
Week 24, 
36, 48… 
every 12 
weeks 
(In-clinic) 
Visit # 
1 
2 
3 
4 
5 
6 
7 
8, 9, 10… 
– 
– 
– 
Day 
-14 or -56 
1 
8 
15 
29 
57 
84 
168, 252, 
336… 
 
(Last 
dose 
+40 
days) 
 
Visit Windowf 
±3d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
 
±7d 
 
Procedure/activity 
Neisseria meningitidis 
vaccinationk 
X 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
 
 
Pregnancy testl 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
 
Clinical laboratory tests 
(hematology, clinical 
chemistry, and urinalysis)m, n 
X 
 
 
X 
 
 
X 
 
X 
 
X 
Complete physical 
examinationn 
X 
 
 
 
 
 
X 
 
X 
X 
X 
Vital signs 
X 
X 
 
 
 
 
X 
 
X 
X 
X  
12-lead ECGn 
X 
 
 
X 
 
 
X 
 
X 
X 
 
Adverse eventso 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
C-SSRSp 
X 
X 
 
 
 
 
X 
X  
X 
X 
 
MG-ADLr 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
QMG scaleq, r 
 
X 
 
X 
 
 
X 
 
X 
 
X 
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Table 1‒2: 
Schedule of Activities 
Study Period 
Screening 
Perioda 
Main Treatment Period 
Extension 
Treatment 
Period 
EW/ 
With-
drawal 
Visitb,w 
(In-
clinic) 
SFU 
Visit 
(In-
clinic)c 
Rescue 
Therapy 
Visit (If 
applicable
)d 
Visit name 
Screening 
Visit 
(In-clinic) 
Baselinee 
(In-clinic) 
Week 1 
(Phone 
call) 
Week 
2 (In-
clinic) 
Week 
4 
(Phone 
call) 
Week 
8 
(Phone 
call) 
Week 
12 (In-
clinic) 
Week 24, 
36, 48… 
every 12 
weeks 
(In-clinic) 
Visit # 
1 
2 
3 
4 
5 
6 
7 
8, 9, 10… 
– 
– 
– 
Day 
-14 or -56 
1 
8 
15 
29 
57 
84 
168, 252, 
336… 
 
(Last 
dose 
+40 
days) 
 
Visit Windowf 
±3d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
 
±7d 
 
Procedure/activity 
MG-QOL15rr 
 
X 
 
X 
 
 
X 
 
X 
 
X 
MGFA Post-Intervention 
Status 
 
 
 
 
 
 
X 
 
X 
 
X 
TSQM-9r 
 
X 
 
 
 
 
X 
 
X 
 
  
Patient Preference 
assessmentr 
 
 
 
 
 
 
X 
 
X 
 
 
Blood sampling for PKs,t 
 
 
 
X 
 
 
X 
 
X 
 
X 
Blood sampling for PDs,t 
(sRBC lysis assay) 
 
X 
 
X 
 
 
X 
 
X 
 
X 
Last regularly scheduled IV 
C5 inhibitor administrationu 
X 
 
 
 
 
 
 
 
 
 
 
SC ZLP dispensedx 
 
X 
 
X  
 
 
X 
X 
 
 
 
SC ZLP administrationv 
 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
Time needed for 
administration of SC ZLP 
 
 
 
X 
 
 
X 
 
 
 
 
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Table 1‒2: 
Schedule of Activities 
Study Period 
Screening 
Perioda 
Main Treatment Period 
Extension 
Treatment 
Period 
EW/ 
With-
drawal 
Visitb,w 
(In-
clinic) 
SFU 
Visit 
(In-
clinic)c 
Rescue 
Therapy 
Visit (If 
applicable
)d 
Visit name 
Screening 
Visit 
(In-clinic) 
Baselinee 
(In-clinic) 
Week 1 
(Phone 
call) 
Week 
2 (In-
clinic) 
Week 
4 
(Phone 
call) 
Week 
8 
(Phone 
call) 
Week 
12 (In-
clinic) 
Week 24, 
36, 48… 
every 12 
weeks 
(In-clinic) 
Visit # 
1 
2 
3 
4 
5 
6 
7 
8, 9, 10… 
– 
– 
– 
Day 
-14 or -56 
1 
8 
15 
29 
57 
84 
168, 252, 
336… 
 
(Last 
dose 
+40 
days) 
 
Visit Windowf 
±3d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
 
±7d 
 
Procedure/activity 
Date of first receipt of rescue 
therapy 
 
 
 
 
 
 
 
 
 
 
X 
AChR=acetylcholine receptor; AE=adverse event; ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
C5=complement component 5; COVID-19=coronavirus disease 2019; C-SSRS=Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; EW=Early 
Withdrawal; FDA=Food and Drug Administration; gMG=generalized myasthenia gravis; IV=intravenous; MG=myasthenia gravis; MG-ADL=Myasthenia 
Gravis-Activities of Daily Living; MGFA=Myasthenia Gravis Foundation of America; MG-QOL15r=Myasthenia Gravis-Quality of Life Revised; 
PD=pharmacodynamic(s); PLEX=plasma exchange; PK=pharmacokinetic(s); QMG=Quantitative Myasthenia Gravis; SAE=serious adverse event; 
SC=subcutaneous(ly); SFU=Safety Follow-up; SOC=standard of care; sRBC=sheep red blood cell; TSQM-9=9-item Treatment Satisfaction Questionnaire for 
Medication; ZLP=zilucoplan 
a The Screening Visit should be scheduled to coincide with the regularly scheduled study participant IV C5 inhibitor administration (±3 days) (Figure 1‒1). 
b If a study participant permanently withdraws from the study prior to the Week 12 visit, the study participant should return to the clinic for an EW Visit as soon 
as possible but no later than the next scheduled visit. 
c Study participants who discontinue ZLP at any point in the study will be required to return to the clinic for a SFU Visit performed at 40±7 days after their last 
dose to gather additional safety information, including information about on ongoing AEs and the reporting any new SAEs since the last study visit. 
d For study participants who require rescue therapy (see Section 6.5.4), a Rescue Therapy Visit should be conducted prior to the initiation of rescue therapy. If 
the Rescue Therapy Visit coincides with a regularly scheduled study visit, then overlapping study procedures do not need to be duplicated. The study 
participant will continue ZLP treatment while undergoing rescue therapy if it is considered by the Investigator to be in his/her best interest. 
e In circumstances where COVID-19 disruptions lead to a study participant being unable to return for Day 1 after 14 or 56 days of the Screening Period, 
respectively, additional days may be included in the Screening Period. Contact with the Medical Monitor is requested in such situations. 
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Table 1‒2: 
Schedule of Activities 
Study Period 
Screening 
Perioda 
Main Treatment Period 
Extension 
Treatment 
Period 
EW/ 
With-
drawal 
Visitb,w 
(In-
clinic) 
SFU 
Visit 
(In-
clinic)c 
Rescue 
Therapy 
Visit (If 
applicable
)d 
Visit name 
Screening 
Visit 
(In-clinic) 
Baselinee 
(In-clinic) 
Week 1 
(Phone 
call) 
Week 
2 (In-
clinic) 
Week 
4 
(Phone 
call) 
Week 
8 
(Phone 
call) 
Week 
12 (In-
clinic) 
Week 24, 
36, 48… 
every 12 
weeks 
(In-clinic) 
Visit # 
1 
2 
3 
4 
5 
6 
7 
8, 9, 10… 
– 
– 
– 
Day 
-14 or -56 
1 
8 
15 
29 
57 
84 
168, 252, 
336… 
 
(Last 
dose 
+40 
days) 
 
Visit Windowf 
±3d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
 
±7d 
 
Procedure/activity 
f The visit windows provided are with respect to the Baseline Visit with the exception of the SFU Visit, in which the visit window applies to 40 days after the 
last dose of study medication. 
g Procedures performed as SOC during the Screening Period may be used to determine eligibility. Informed consent must be obtained prior to performing any 
study-specific procedures that are not SOC. 
h Screening includes disease history with documented diagnosis of gMG by the MGFA criteria (Class II-IVa) and documented serology for AChR 
autoantibodies. 
i Height will be measured only at Screening.  
j All prescriptions and over-the-counter medications taken during the 30 days prior to Screening through the last study visit will be documented. Note: A 
complete history of medications taken for the treatment of gMG will be collected. 
k To reduce the risk of meningococcal infection (Neisseria meningitidis), all study participants must be vaccinated against meningococcal infections, with at least 
1 dose of quadrivalent meningococcal vaccine and meningococcal serotype B vaccine at least 14 days prior to the first dose of ZLP if not vaccinated within 
3 years prior to the start of study medication. The second dose of the primary vaccination cycle can be administered during the study. Participants who initiate 
study medication less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics (eg, penicillin V 
500mg twice daily, third generation cephalosporin) until at least 2 weeks after the initial dose of vaccine(s). The use of fluoroquinolone or macrolide antibiotics 
is not recommended due to the potential for exacerbation of MG. Booster vaccinations should be administered in accordance with the most current relevant 
guideline (ie, Advisory Committee on Immunization Practices, United States). 
l For all female study participants of childbearing potential, a negative serum pregnancy test must be documented at Screening. All other pregnancy tests will be 
performed via urine. At the Week 2 Visit, study participants will receive a home pregnancy testing kit with instruction to complete the test on the day of the 
Week 8 Visit prior to the conduct of the phone call visit, such that the result will be available to report to the site staff during the call. 
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Table 1‒2: 
Schedule of Activities 
Study Period 
Screening 
Perioda 
Main Treatment Period 
Extension 
Treatment 
Period 
EW/ 
With-
drawal 
Visitb,w 
(In-
clinic) 
SFU 
Visit 
(In-
clinic)c 
Rescue 
Therapy 
Visit (If 
applicable
)d 
Visit name 
Screening 
Visit 
(In-clinic) 
Baselinee 
(In-clinic) 
Week 1 
(Phone 
call) 
Week 
2 (In-
clinic) 
Week 
4 
(Phone 
call) 
Week 
8 
(Phone 
call) 
Week 
12 (In-
clinic) 
Week 24, 
36, 48… 
every 12 
weeks 
(In-clinic) 
Visit # 
1 
2 
3 
4 
5 
6 
7 
8, 9, 10… 
– 
– 
– 
Day 
-14 or -56 
1 
8 
15 
29 
57 
84 
168, 252, 
336… 
 
(Last 
dose 
+40 
days) 
 
Visit Windowf 
±3d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
 
±7d 
 
Procedure/activity 
m Samples for hematology, clinical chemistry, and urinalysis should be obtained prior to administration of study medication at applicable visits. Clinical 
chemistry tests include AST/serum glutamic-oxaloacetic transaminase, ALT/serum glutamic-pyruvic transaminase, ALP, total and direct bilirubin, amylase, 
and lipase. 
n Clinical laboratory, physical examination, and ECG assessments conducted at Screening will be considered the baseline values for evaluating of the other safety 
endpoints. 
o All AEs and SAEs should be monitored until resolution or stabilization. Serious AEs that occur within 40 days after the last dose of study medication should be 
reported using the procedures outlined in Appendix 3 (Section 10.3). 
p In accordance with the draft FDA Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials Guidance (Food and Drug 
Administration, Guidance for Industry, 2012) study participants will be asked to complete the C-SSRS at study visits as specified. 
q The QMG should be performed at approximately the same time of day prior to dosing (preferably in the morning) and administered by the same well-trained 
evaluator (eg, neurologist, physical therapist, or other study staff) at each visit throughout the study. 
r Myasthenia Gravis-Quality of Life Revised, TSQM-9, Patient Preference assessment, QMG, and MG-ADL should be performed prior to dosing and prior to 
any other study procedures. 
s For local Rescue Therapy Visits only, blood samples for PK and PD analyses will be collected within 1 hour prior to administration of each round of rescue 
therapy. If a study participant receives PLEX treatment as rescue therapy, PK will be measured in the exchanged plasma. If rescue therapy is administered at a 
location separate from the clinical site, then there is no need to collect blood samples for PK/PD analyses. 
t Blood samples for PK and PD analyses will be obtained at planned visits prior to dosing (within 1 hour of dosing). Back-up specimens may be retained for 
future exploratory biomarker analyses. 
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Table 1‒2: 
Schedule of Activities 
Study Period 
Screening 
Perioda 
Main Treatment Period 
Extension 
Treatment 
Period 
EW/ 
With-
drawal 
Visitb,w 
(In-
clinic) 
SFU 
Visit 
(In-
clinic)c 
Rescue 
Therapy 
Visit (If 
applicable
)d 
Visit name 
Screening 
Visit 
(In-clinic) 
Baselinee 
(In-clinic) 
Week 1 
(Phone 
call) 
Week 
2 (In-
clinic) 
Week 
4 
(Phone 
call) 
Week 
8 
(Phone 
call) 
Week 
12 (In-
clinic) 
Week 24, 
36, 48… 
every 12 
weeks 
(In-clinic) 
Visit # 
1 
2 
3 
4 
5 
6 
7 
8, 9, 10… 
– 
– 
– 
Day 
-14 or -56 
1 
8 
15 
29 
57 
84 
168, 252, 
336… 
 
(Last 
dose 
+40 
days) 
 
Visit Windowf 
±3d 
±2d 
±2d 
±2d 
±2d 
±2d 
±2d 
±7d 
 
±7d 
 
Procedure/activity 
u Up to and including the time of the Screening Visit, study participants will continue to receive their IV C5 inhibitor at the recommended dose regimen. The last 
regularly scheduled IV C5 inhibitor administration cannot occur beyond the Screening Visit (±3 days) to ensure approximately a 2-week (for eculizumab) or 
8-week (for ravulizumab) interval between the last regularly scheduled IV C5 inhibitor administration and the first SC ZLP administration at the Baseline Visit, 
respectively). 
v Following the first in-clinic administration of ZLP at Baseline and in-clinic education and training, all study participants will self-inject daily SC doses of study 
medication. During the Main Treatment Period, dosing on in-clinic study visit days should be withheld until all assessments have been completed. On days 
when rescue therapy is concurrently administered, dosing should be withheld until after administration of rescue therapy and PK/PD sampling. 
w Participants who withdraw during the Extension Treatment Period will complete a Withdrawal Visit as soon as possible but no later than the next scheduled 
visit. At the Withdrawal Visit, only the following study assessments need to be completed: prior and concomitant medications, weight, pregnancy testing (for 
women of childbearing potential), C-SSRS, and collection of AEs. 
x At the Week 12 Visit, ZLP dispensation only occurs for study participants continuing into the Extension Treatment Period. 
 
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2 
INTRODUCTION 
2.1 
Study rationale 
Myasthenia gravis is a serious, sometimes life-threatening, debilitating condition associated with 
numerous symptoms including muscular weakness and fatigue. There remains a need for safe 
and effective treatments to conveniently treat patients with MG, including gMG, where the 
disease progresses beyond the ocular muscles and affects multiple muscle groups throughout the 
body. Some patients can manage their symptoms with oral medications such as an oral 
acetylcholinesterase inhibitors, corticosteroids, or nonsteroidal immunosuppressants. In addition, 
intravenous immunoglobulin G (IVIG) and plasma exchange (PLEX) treatment could be utilized 
as well. For those whose symptoms are not well managed by these medications, a potential 
alternative is long term treatment with approved IV C5 inhibitors (eg, eculizumab or 
ravulizumab) which have proven effective at treating MG symptoms. However, there remains a 
need for new therapeutic options available to patients for whom IV infusions represent a high 
administration burden, have difficult venous access, or who are in underserved or rural 
populations where economic access to IV infusions is prohibitive. MG0017 aims to evaluate the 
disease control and safety and tolerability after switching from an approved IV C5 inhibitor to 
SC ZLP, as well as the evaluation of patient satisfaction and preference. 
2.2 
Background 
Myasthenia gravis is a rare complement-mediated autoimmune disease characterized by the 
production of autoantibodies targeting proteins that are critical for the normal transmission of 
neurotransmitter signals from nerves to muscles. The prevalence of MG in the US and EU is 
estimated at approximately 60,000 and 191,000 cases, respectively. In 15% of patients with MG, 
symptoms remain confined to the ocular muscles. In approximately 85% of patients, MG 
progresses beyond the ocular muscles to affect multiple muscle groups throughout the body, a 
condition that is typically referred to as gMG (Gilhus, 2016). 
Patients with gMG present with muscle weakness that characteristically becomes more severe 
with repeated use and recovers with rest. Symptoms are typically at their mildest in the morning, 
when overnight inactivity enables replenishment of acetylcholine levels in presynaptic motor 
nerve terminals, and worsen during the course of the day. Muscle weakness can be localized to 
specific muscles, but often progresses to more diffuse muscle weakness (Gilhus, 2016; Gilhus 
and Verschuuren, 2015; Chamanza et al, 2010). Generalized MG symptoms can become 
life-threatening when muscle weakness involves the diaphragm and intercostal muscles in the 
chest wall that are responsible for breathing. The most dangerous complication of gMG, known 
as myasthenic crisis, requires hospitalization, intubation, and mechanical ventilation. 
Approximately 15% to 20% of patients with gMG will experience a myasthenic crisis within 
2 years of diagnosis (Ramizuddin, 2014). 
Zilucoplan (RA101495) is a 15-amino acid macrocyclic peptide complement inhibitor designed 
for the treatment of conditions in which inappropriate activation of C5 has been demonstrated to 
play a role. Zilucoplan binds to C5 with high affinity and prevents its cleavage by C5 
convertases into the cleavage products C5a and C5b. Inhibition of C5 cleavage prevents the 
downstream assembly and cytolytic activity of the membrane attack complex. 
Pharmacologically, ZLP has demonstrated dose-dependent inhibition of C5a and C5b formation 
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following activation of classical or alternative complement pathways, as well as inhibition of red 
blood cell lysis in the serum/plasma from various species. 
Zilucoplan is being investigated in patients with amyotrophic lateral sclerosis and gMG, and also 
other complement-mediated diseases are being considered. 
Inhibition of C5 for the treatment of gMG has already been shown to be effective in clinical 
studies with the C5-blocking antibodies, eculizumab (Howard, 2018; Howard et al, 2013) and 
ravulizumab (Vu et al, 2022), which established that inhibition of the terminal complement 
cascade by blocking cleavage of C5 is a clinically validated approach for treating gMG. 
However, unlike eculizumab and ravulizumab, ZLP provides patients with the advantages of SC 
self-administration at home. 
The clinical efficacy of ZLP in gMG has been shown in a Phase 2 study, MG0009 (previously 
RA101495-02.201), and in a Phase 3 study, MG0010 (previously RA101495-02.301). In 
addition, ZLP has shown a favorable safety and tolerability profile across all completed studies. 
Further details are provided in the ZLP Investigator’s Brochure (IB). 
2.3 
Benefit/risk assessment 
Zilucoplan is being developed to treat patients with gMG. 
In the Phase 2 study, MG0009, ZLP 0.3mg/kg/day showed a statistically significant and 
clinically meaningful benefit as measured by improvement on the primary endpoint, the 
Quantitative Myasthenia Gravis (QMG) score, compared to placebo over 12 weeks, as well as on 
the MG-ADL (key secondary endpoint), the Myasthenia Gravis-Quality of Life Revised 
(MG-QOL15r), and the Myasthenia Gravis Composite (MGC) score (Howard et al, 2020). 
In the pivotal Phase 3 study, MG0010, a clinically meaningful and statistically significant 
improvement from Baseline in MG-ADL total score at Week 12 (primary endpoint) was 
observed for the ZLP treatment group (ZLP 0.3mg/kg/day) vs placebo. Significant improvements 
from Baseline in QMG, MGC, and MG-QoL15r scores were also observed at Week 12 for the 
ZLP treatment group vs placebo. Zilucoplan was well tolerated, and no major unexpected safety 
findings were identified compared to earlier ZLP studies. 
Moreover, in both of these studies, the placebo-corrected clinical efficacy of ZLP 0.3mg/kg/day 
administered SC as measured by the QMG and MG-ADL at Week 12 was numerically superior 
to the efficacy observed in the Phase 3 study with the approved IV C5 inhibitors eculizumab and 
ravulizumab at Week 26 after treatment initiation with a similar safety and tolerability profile 
(Howard et al, 2017; Vu et al, 2022). 
Given the known increased risk of meningococcal infection (Neisseria meningitidis) associated 
with inhibition or inherited deficiency of C5, participants who participate in this study with ZLP 
will be required to have documentation of at least 1 dose of N. meningitidis vaccination at least 
2 weeks prior to study medication administration. In addition, while on treatment with ZLP, 
study participants will be monitored closely for signs and symptoms of N. meningitidis infection. 
A study participant safety card detailing the signs and symptoms of infection, with instructions to 
seek immediate medical attention if any such symptoms occur, will be provided to each study 
participant. Study participants must be vaccinated with at least 1 dose each of quadrivalent 
meningococcal vaccine and meningococcal serotype B vaccine against N. meningitidis at least 
14 days before the first administration of SC ZLP if not vaccinated within 3 years prior to the 
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start of study medication. The second dose of the primary vaccination cycle can be administered 
during the study. Booster vaccinations should be administered according to the most current 
relevant guideline (ie, Advisory Committee on Immunization Practices, United States). 
(Section 1.3). 
Given the safety and tolerability profile of ZLP, the efficacy data from the Phase 2 study, 
MG0009, the Phase 3 study, MG0010, and the efficacy and safety profile of IV C5 inhibitors 
approved for the treatment of gMG, 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 ZLP can be found in the IB. 
3 
OBJECTIVES AND ENDPOINTS 
Table 3‒1: 
Objectives and estimands/endpoints 
Objectives 
Estimands/endpoints 
Primary 
To evaluate the safety and 
tolerability of switching from IV 
C5 inhibitors to SC ZLP in study 
participants with gMG 
The primary safety endpoints are: 
• 
Incidence of TEAEs over the Main Treatment Period 
• 
Incidence of TEAEs leading to withdrawal of study medication 
over the Main Treatment Period 
Secondary 
To evaluate the efficacy of SC 
ZLP after switching from IV C5 
inhibitors in study participants 
with gMG 
The secondary efficacy estimand is: 
• 
Treatment: ZLP administered by daily SC injections 
(0.3mg/kg/day) 
• 
Target population: Adult study participants with gMG currently 
receiving an IV C5 inhibitor approved for the treatment of 
gMG according to the protocol-specified inclusion/exclusion 
criteria 
• 
Endpoint: CFB to Week 12 in MG-ADL score 
• 
Intercurrent event handling: The intercurrent events considered 
in this study are: 
− 
Administration of rescue therapy or changes in SOC dose 
regimens. Data collected at and after the point of the 
intercurrent event will be used as collected to gain 
understanding of clinical practice. 
− 
Participant discontinuation from the study. It will be 
assumed that the participant had remained on their 
treatment (regardless of rescue therapy administration) 
throughout the study (ie, a "hypothetical strategy" 
assuming participants did not discontinue the study and 
remained on treatment). 
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Table 3‒1: 
Objectives and estimands/endpoints 
Objectives 
Estimands/endpoints 
• 
Population level summary: The mean of the endpoint 
To evaluate the efficacy of SC 
ZLP after switching from IV C5 
inhibitors on an additional 
efficacy endpoint in study 
participants with gMG 
The secondary efficacy endpoint is: 
• 
CFB to Week 12 in the QMG score 
This endpoint will be analyzed following the same estimand 
structure as defined for the MG-ADL score. The endpoint assessed 
will change accordingly. 
To evaluate safety and 
tolerability of SC ZLP after 
switching from IV C5 inhibitors 
on additional safety measures in 
study participants with gMG 
The secondary safety endpoints are: 
• 
Incidence of serious TEAEs over the Main Treatment Period 
• 
Incidence of study withdrawal over the Main Treatment Period 
Other 
To further explore the efficacy of 
SC ZLP on additional efficacy 
endpoints after switching from 
IV C5 inhibitors in study 
participants with gMG 
The other efficacy endpoints are: 
• 
Time to first receipt of rescue therapy over the Main Treatment 
Period 
• 
Change in SOC therapy medication dose regimen for gMG 
during the Main Treatment Period 
• 
Achievement of Minimal Manifestation Status per MGFA-PIS 
at Week 12 without rescue therapy 
• 
Achieving MSE, defined as an MG-ADL of 0 or 1 at Week 12 
without rescue therapy 
• 
CFB to Week 12 in QMG subscores: ocular, bulbar, 
respiratory, limb 
• 
CFB to Week 12 in MG-QOL15r score 
• 
MG-ADL score responder rate (responder is defined as 
achieving ≥ 3-point improvement from Baseline [decrease] at 
Week 12 and not having taken rescue therapy) 
• 
QMG score responder rate (responder is defined as achieving  
≥5-point improvement from Baseline [decrease] at Week 12 
and not having taken rescue therapy) 
To explore the time needed for 
administration of SC ZLP 
The other endpoint is: 
• 
Time needed for administration of SC ZLP 
To explore study participants’ 
treatment satisfaction following 
the use of SC ZLP 
The other endpoint is: 
• 
CFB to Week 12 in TSQM-9 scores 
To explore study participant 
preference following the use of 
SC ZLP 
The other endpoint is: 
• 
Patient Preference assessment at Week 12 
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Table 3‒1: 
Objectives and estimands/endpoints 
Objectives 
Estimands/endpoints 
To further evaluate the safety 
and tolerability of SC ZLP after 
switching from IV C5 inhibitors 
on other safety measures in 
study participants with gMG 
The other safety endpoints are: 
• 
CFBa to Week 12 in clinical laboratory tests 
• 
CFBa to Week 12 in physical examination 
• ECGa 
• 
C-SSRS 
• 
Incidence of TEAEs 
To evaluate the PK of SC ZLP 
after switching from IV C5 
inhibitors 
The other PK endpoint is: 
• 
Plasma concentrations of ZLP and its major metabolites over 
the Main Treatment Period 
 
To evaluate the PD of SC ZLP 
after switching from IV C5 
inhibitors 
The other PD endpoint is: 
• 
sRBC lysis assay for evaluation of classical complement 
pathway activation over the Main Treatment Period 
a In this study, the clinical laboratory, physical examination, and ECG assessments conducted at Screening will be 
considered the baseline values for evaluating of the other safety endpoints. 
C5=complement component 5; CFB=change from Baseline; C-SSRS=Columbia-Suicide Severity Rating Scale; 
ECG=electrocardiogram; gMG=generalized myasthenia gravis; IV=intravenous; MG-ADL=Myasthenia 
Gravis-Activities of Daily Living; MG-QOL15r=Myasthenia Gravis – Quality of Life revised; 
MGFA-PIS=Myasthenia Gravis Foundation of America Post-Intervention Status; MSE=Minimal Symptom 
Expression; PD=pharmacodynamic(s); PK=pharmacokinetic(s); QMG= Quantitative Myasthenia Gravis; 
SC=subcutaneous; SOC=standard of care; sRBC=sheep red blood cell; TEAE=treatment-emergent adverse 
event; TSQM-9=9-item Treatment Satisfaction Questionnaire for Medication; ZLP=zilucoplan 
3.1 
Estimand/intercurrent event handling rationale and impact on 
the study 
The estimand corresponding to the efficacy objective to evaluate the efficacy of SC ZLP after 
switching from IV C5 inhibitors in study participants with gMG, is described below: 
• Treatment: ZLP administered by daily SC injections (0.3mg/kg/day). 
• Target population: Adult study participants with gMG currently receiving an IV C5 inhibitor 
approved for the treatment of gMG according to the protocol-specified inclusion/exclusion 
criteria. 
• Endpoint: Change from Baseline (CFB) to Week 12 in MG-ADL score. 
• Intercurrent event handling: The intercurrent events considered in this study are: 
− Administration of a rescue therapy (Section 6.5.4) or changes in standard of care (SOC) 
dose regimens. Data collected at and after the point of the intercurrent event will be used 
as collected to gain understanding of clinical practice. 
− Participant discontinuation from the study. It is assumed that the participant had remained 
on their treatment (regardless of rescue therapy administration) throughout the study (ie, 
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a "hypothetical strategy" assuming participants did not discontinue the study and 
remained on treatment). 
• Population-level summary: The mean of the endpoint. 
One of the efficacy objectives of this Phase 3b study is to evaluate the efficacy of SC ZLP after 
switching from IV C5 inhibitors in study participants with gMG who are willing to switch to SC 
ZLP in a situation which can be common in clinical practice (with the arrival of new therapeutic 
agents). Thus, the intercurrent event handling strategy to consider data after the use of rescue 
therapy in the analysis and to assume that the study participant had remained on their treatment 
or on rescue therapy after study discontinuation is aligned with the study objective. 
The same estimand structure defined for the MG-ADL score will be used to analyze the endpoint 
of CFB to Week 12 in QMG score. 
4 
STUDY DESIGN 
4.1 
Overall design 
MG0017 is a Phase 3b, multicenter, open-label, single-arm study to evaluate the safety, 
tolerability, and efficacy of ZLP in study participants with gMG switching from their current IV 
C5 inhibitor to SC ZLP. 
To be eligible to participate in this study, participants must be adults (≥18 years of age) with a 
documented diagnosis of gMG (Myasthenia Gravis Foundation of America [MGFA] 
Class II-IVa), currently receiving an IV C5 inhibitor approved for the treatment of gMG for at 
least 3 months (for eculizumab) or 4 months (for ravulizumab) prior to Screening (with the last 
dose being administered at the Screening Visit ±3 days), considered to have a clinically stable 
disease as per the Investigator’s judgment prior to Screening, and willing to switch from their 
current IV C5 inhibitor to SC ZLP. 
The planned enrollment is 20 study participants in the US. 
The study includes a 2-week or 8-week Screening Period (for participants receiving eculizumab 
or ravulizumab, respectively), a 12-week Main Treatment Period, and an optional Extension 
Treatment Period. A SFU Visit should be performed 40 days (±7 days) after the last dose of 
study medication (Section 6.8, Section 1.2). 
The Screening Visit should be scheduled to coincide with the regularly scheduled study 
participant’s IV C5 inhibitor administration (±3 days). Up to and including the time of the 
Screening Visit, study participants will continue to receive their IV C5 inhibitor at the 
recommended dose regimen. The last regularly scheduled IV C5 inhibitor administration cannot 
occur beyond Day -14 (±3 days) of the Screening Period for study participants receiving 
eculizumab or beyond Day -56 (±3 days) of the Screening Period for study participants receiving 
ravulizumab to ensure approximately a 2-week or 8-week interval between the last regularly 
scheduled IV C5 inhibitor administration (administered at the Screening Visit ±3 days) and the 
first SC ZLP administration at the Baseline Visit, respectively. 
At the end of the Screening Period and in case of no more than a 2-point change in study 
participants’ MG-ADL score compared to the Screening Visit, study participants will enter the 
Main Treatment Period and will switch to SC ZLP (IV C5 inhibitor should not be administered 
after the Screening Visit). On Day 1, study participants will receive ZLP 0.3mg/kg administered 
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SC. Following in-clinic education and training, all study participants will self-inject daily SC 
doses of study medication for the subsequent 12 weeks. Single-use pre-filled syringes in 
injection devices will be provided for use during the study. Of note, there will be no washout 
period during the study where study participants are not receiving treatment for MG. 
During the Main Treatment Period, study participants will be contacted via phone call at Week 1, 
Week 4, and Week 8 to assess safety and tolerability. During these phone call visits, the 
MG-ADL assessment will also be performed. Study participants will return to the clinic at 
Week 2 and Week 12 to evaluate safety, tolerability, and efficacy. Additional assessments will 
include questionnaires, PK, and PD. Safety assessments will include AE monitoring, physical 
examination, clinical laboratory tests, and Columbia-Suicide Severity Rating Scale (C-SSRS) in 
accordance with the Schedule of Activities (Section 1.3). 
The time needed for preparation and administration of SC ZLP will also be measured during the 
Screening Period and Main Treatment Period in accordance with the Schedule of Activities 
(Section 1.3). 
Study participants are expected to remain on a stable dose regimen of all medications unless 
medically indicated changes become necessary. All SOC therapy medications for gMG should 
be kept at the same dose regimen throughout the Main Treatment Period, including 
corticosteroids and immunosuppressant therapy (IST) drugs. If rescue therapy becomes 
necessary due to major deterioration of a study participant’s clinical status, or risk of MG crisis 
as per the Investigator’s judgment, the study participant may receive IVIG or PLEX treatment as 
rescue therapy (Section 6.5.4). 
Additionally, if deemed needed as per the Investigator’s judgment, study participant may be 
readministered their previous IV C5 inhibitor or administered a different IV C5 inhibitor after 
discontinuation of the study medication. 
All study participants who complete the 12-week Main Treatment Period without discontinuing 
study medication will have the option to continue ZLP treatment in the Extension Treatment 
Period after the Week 12 visit. Participants who withdraw during the Main Treatment Period will 
complete an EW Visit followed by a SFU Visit 40 days (±7 days) after the last dose of study 
medication. Participants who opt not to continue into the Extension Treatment Period will 
complete a SFU Visit 40 days (±7 days) after the last dose of study medication. 
The Extension Treatment Period consists of in-clinic visits every 12 weeks (±7 days) and will 
continue until all participants are withdrawn, until ZLP is approved and available in the US, or 
until further notice from the Sponsor. During these visits, ZLP accountability and resupply will 
be performed, medications updated, and safety will be assessed. Participants who withdraw or 
discontinue ZLP during the Extension Treatment Period will complete a Withdrawal Visit 
followed by a SFU Visit 40 days (±7 days) after the last dose of study medication. Participants 
who transition to commercially available ZLP will complete a Withdrawal Visit but will not 
require a SFU Visit. If by the time a participant completes the Main Treatment Period ZLP is 
commercially available, the participant may transition to commercially available ZLP directly 
following the Week 12 visit at the end of the Main Treatment Period. 
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4.2 
Scientific rationale for study design 
The clinical efficacy, safety, and tolerability of ZLP 0.3mg/kg/day administered SC has been 
evaluated over 12 weeks in both MG0009 and MG0010. These studies demonstrated a 
statistically significant and clinically meaningful benefit of ZLP treatment on efficacy measures 
and a favorable safety and tolerability profile over placebo (Section 2.3). MG0017 is an 
open-label, single-arm study to evaluate the safety, tolerability, and efficacy of ZLP in study 
participants with gMG switching from their current IV C5 inhibitor to SC ZLP. The open-label, 
single-arm design without the inclusion of a placebo control is acceptable for this study since SC 
ZLP has already been shown to be numerically superior to the efficacy observed with the 
approved IV C5 inhibitors eculizumab and ravulizumab (Section 2.3), and it also allows all study 
participants to continue to receive an effective treatment (as opposed to an inert control). The 
12-week treatment duration of the Main Treatment Period in this study was chosen as it is 
consistent with the pivotal Phase 3 study (MG0010). In the MG0010 study, a rapid separation of 
efficacy between ZLP and placebo was observed after 1 week which was maximized within 4 
weeks and was then maintained through the course of the 12-week study. The rationale for dose 
selection in this study is provided in Section 4.3. The Extension Treatment Period was added to 
provide access to ZLP for participants with gMG who have completed the Main Treatment 
Period and who wish to continue receiving ZLP. 
The study population will include adults with gMG who have been receiving an IV C5 inhibitor 
approved for the treatment of gMG for at least 3 months (for eculizumab) or 4 months (for 
ravulizumab) prior to Screening with a clinically stable disease as per the Investigator’s 
judgment. Only study participants who are willing to switch from their current IV C5 inhibitor to 
SC ZLP will be included in the study. There is no minimum number of study participants 
switching from either eculizumab or ravulizumab in this study in order to keep with real world 
clinical practice for the treatment of patients with gMG. 
4.3 
Justification for dose 
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4.4 
End of study definition 
Completion of main treatment period for the participant 
A participant is considered to have completed the Main Treatment Period if he/she completed 
the Week 12 visit and: 
• Decided to enter the Extension Treatment Period. 
OR 
• Transitioned to commercially available ZLP directly after the Week 12 visit (no Withdrawal 
or SFU visit required). 
OR 
• Decided not to enter the Extension Treatment Period and completed a SFU visit. 
Completion of study for the participant 
A participant is considered to have completed the study if he/she completed the Main Treatment 
Period and: 
• Did not enter the Extension Treatment Period. 
OR 
• Entered the Extension Treatment Period and: 
− withdrew from the Extension Treatment Period, discontinued ZLP, and completed the 
Withdrawal and SFU Visits. 
OR 
− transitioned to commercially available ZLP and completed the Withdrawal Visit. No SFU 
Visit is required. 
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End of study 
The end of the study is defined as the date of the last visit of the last participant in the study. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be between 18 years and 85 years of age, inclusive, at the time of signing 
the Informed Consent form (ICF). 
Type of participant and disease characteristics 
2a. Participant has been treated with an IV C5 inhibitor approved for the treatment of gMG at the 
recommended dose regimen for at least 3 months (for eculizumab) or 4 months (for 
ravulizumab) prior to Screening with a clinically stable disease as per the Investigator’s 
judgment. 
NOTE: The last dose of the IV C5 inhibitor must be taken at the Screening Visit (±3 days) 
(Section 4.1). Participant is willing to switch from his/her current IV C5 inhibitor to SC ZLP. 
4. Participant has a documented diagnosis of gMG (MGFA Class II-IVa) at Screening based on 
participant history and supported by previous evaluations. 
5. Participant has a well-documented record of positive serology for acetylcholine receptor 
binding autoantibodies prior to Screening. 
6. Participant has no more than a 2-point change in MG-ADL score at Baseline compared with 
the Screening Visit. 
7a. Participant has had no change in corticosteroid dose during the Screening Period and no 
change in corticosteroid dose is anticipated to occur during the 12-week Main Treatment 
Period. 
8a. Participant has had no change in immunosuppressive therapy, including dose, during the 
Screening Period and no change in immunosuppressive therapy is anticipated to occur during 
the 12-week Main Treatment Period. 
9a. Participant has a record of vaccination with at least 1 dose of a quadrivalent meningococcal 
vaccine and meningococcal serotype B vaccine at least 14 days prior to the first dose of ZLP 
if not vaccinated within 3 years prior to the start of study medication. 
Participants who initiate study medication less than 2 weeks after receiving a meningococcal 
vaccine must receive treatment with appropriate prophylactic antibiotics (eg, penicillin V 
500mg twice daily, third generation cephalosporin) until at least 2 weeks after the initial dose 
of vaccine(s). The use of fluoroquinolone or macrolide antibiotics is not recommended due to 
the potential for exacerbation of MG. 
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A booster vaccination should also be administered, as clinically indicated, to participants 
who have been previously vaccinated against N. meningitidis in order to be eligible for 
inclusion in this study. Participants also must agree to receive a booster vaccination during 
the study according to the most current relevant guideline (ie, Advisory Committee on 
Immunization Practices, United States). 
Sex 
10a. Male and/or female 
− A male participant is recommended to agree to use contraception as detailed in 
Appendix 4 (Section 10.4) of this protocol during the study and for at least 40 days 
(5 half-lives) after the last dose of study medication, and refrain from donating sperm 
during this period. 
− A female participant is eligible to participate if she is not pregnant (see Appendix 4 
[Section 10.4]), not breastfeeding, and at least one of the following conditions applies: 
◦ 
Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 
(Section 10.4) 
OR 
A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 
(Section 10.4) during the study and for at least 40 days (5 half-lives) after the last 
dose of study medication. 
Informed consent 
11. Participant is capable of giving signed informed consent as described in Appendix 1 
(Section 10.1), which includes compliance with the requirements and restrictions listed in the 
ICF and in this protocol. 
5.2 
Exclusion criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
1. Participant has any medical or psychiatric condition that, in the opinion of the Investigator, 
could jeopardize or would compromise the participant’s ability to participate in this study. 
2. Participant has a known hypersensitivity to any components of the study medication as stated 
in this protocol. 
3a. Participant has had a thymectomy within 6 months prior to Baseline or has one scheduled to 
occur during the 12-week Main Treatment Period. 
4. Participant has a history of meningococcal disease. 
5. Participant has or has had a current or recent systemic infection within 2 weeks prior to 
Baseline or an infection requiring IV antibiotics within 4 weeks prior to Baseline. 
6. Participant has active malignancy (except curatively resected squamous or basal cell 
carcinoma of the skin) requiring surgery, chemotherapy, or radiation within the prior 
12 months (participants with a history of malignancy who have undergone curative resection 
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or otherwise not requiring treatment for at least 12 months prior to Screening with no 
detectable recurrence are allowed). 
7. Participant has a lifetime history of suicide attempt (including an actual attempt, interrupted 
attempt, or aborted attempt), or has 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 “Screening/Baseline” version of the C-SSRS at Screening. 
8. Participant has alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline 
phosphatase (ALP) >2.5x upper limit of normal (ULN). 
9. Participant has bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%). 
10. 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: Stable chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, 
and chronic stable hepatitis B or C) is acceptable if the participant otherwise meets entry 
criteria. 
For study participants with a baseline result >ULN for ALT, AST, ALP, or total bilirubin, a 
baseline diagnosis and/or the cause of any clinically meaningful elevation must be 
understood and recorded in the electronic case report form (eCRF). 
If a study participant has >ULN ALT, AST, or ALP that does not meet the exclusion limit at 
Screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing 
clinically relevant increase. In case of a clinically relevant increase, inclusion of the study 
participant must be discussed with the Medical Monitor. 
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation.  
11. QTc interval >450msec for male participants, QTc >470msec for female participants, or 
QTc >480 msec in participants with bundle branch block. 
NOTE: The QTc is the QT interval corrected for heart rate according to Fridericia's formula 
(QTcF). It is either machine read or manually overread.  
Prior/Concomitant therapy 
12a.Participant has had recent surgery requiring general anesthesia within 2 weeks prior to 
Screening or is expected to have surgery requiring general anesthesia during the 12-week 
Main Treatment Period. 
13. Participant has received a treatment with an experimental drug within 30 days or 5 half-lives 
of the experimental drug (whichever is longer) prior to Baseline. 
14a. Participant has received treatment with rituximab within 6 months prior to Baseline or 
treatment is planned to occur during the study. 
15. Participant has received treatment with IVIG, SC immunoglobulin, or PLEX 4 weeks prior 
to Baseline or participant is on chronic IVIG, SC immunoglobulin, or PLEX. 
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Prior/Concurrent clinical study experience 
16. Participant has previously participated in this study or participant has previously been 
assigned to treatment in a study of the medication under investigation in this study. 
17. Participant has participated in another study of an investigational study medication (and/or an 
investigational device) within the previous 30 days or is currently participating in another 
study of an investigational study medication (and/or an investigational device). 
Diagnostic assessments 
18. Participant has known positive serology for muscle-specific kinase. 
5.3 
Lifestyle restrictions 
There are no lifestyle restrictions during the study. 
5.4 
Screen failures 
Screen failures are defined as study participants who consent to participate in the clinical study 
but are not subsequently entered in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials 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). 
In case of screen failure, the study participant can be rescreened twice following discussion with 
the UCB Medical Monitor and/or Study Physician. 
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. 
Up to and including the time of the Screening Visit, study participants will continue to receive 
their IV C5 inhibitor at the recommended dose regimen. Study treatment (ZLP) will be 
administered during the Main Treatment and Extension Treatment Periods. 
6.1 
Treatments administered 
The treatment administered in MG0017 is presented in Table 6‒1. 
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Table 6‒1: 
Treatment administered 
Arm name 
Zilucoplan 
Intervention name 
Zilucoplan 
Type 
Drug 
Dose formulation 
Pre-filled syringe 
Unit dose 
strength(s) 
16.6mg in 0.416mL 
23.0mg in 0.574mL 
32.4mg in 0.810mL 
Dosage level 
0.3mg/kg/day 
Route of 
administration 
Subcutaneous injection 
Use 
Experimental 
IMP 
IMP 
Sourcing 
Provided centrally by the Sponsor 
Packaging and 
labeling 
Study medication will be provided in kits containing 7 prefilled syringes. Each 
syringe and kit will be labeled as required per country requirement. 
Excipients 
Former names 
RA101495 
IMP=investigational medicinal product; NIMP=noninvestigational medicinal product 
Zilucoplan 0.3mg/kg/day administered SC is the selected dose for this study. As in other ZLP 
studies, the dose presentation will be selected using the following weight brackets (Table 6‒2). 
Table 6‒2: 
ZLP dose presentations by weight brackets 
Minimum (nominal)  
target dose (mg/kg/day) 
Actual dose (mg) 
Weight range (kg) 
Dose range 
(mg/kg/day) 
0.3 
16.6 
≥43 to <56 
0.30 to 0.39 
0.3 
23.0 
≥56 to <77 
0.30 to 0.41 
0.3 
32.4 
≥77 to 150 
0.22 to 0.42 
Study participants who present with a higher body weight (≥150kg) or a lower body weight 
(<43kg) will be accommodated on a case-by-case basis, in consultation with the Medical 
Monitor. 
Study participants will be instructed to self-inject SC doses daily for the duration of the study. 
The study participant may inject study drug into the abdomen (preferred site), thigh, or upper 
arm. 
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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 medication received, and any discrepancies are reported 
and resolved before use of the study medication. 
Only participants enrolled in the study may receive study medication and only authorized site 
staff may supply or administer study medication. All study medications 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. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study medication accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the Investigational Medicinal Product (IMP) Handling Manual. 
The Investigator (or designee) will instruct the study participant to store the study medication 
following the instructions on the label. 
Further guidance and information for the final disposition of unused study medication are 
provided in the IMP Handling Manual. 
6.2.1 
Drug accountability 
The eCRF will be used to record study medication dispensing and return information on a 
by-participant basis and will serve as source documentation during the course of the study. 
Details of any study medication lost, damaged (due to breakage or wastage), not used, partially 
used, disposed of at the study site, or returned to the Sponsor or designee must also be recorded 
on the appropriate forms. All supplies and pharmacy documentation must be made available 
throughout the study for UCB (or designee) to review. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of study medication until returned or destroyed. 
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The Investigator must ensure that the 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 (SOPs) or returned to UCB (or designee). Study medication intended for the study 
cannot be used for any other purpose than that described in this protocol. 
For further details about drug accountability, refer to the IMP Handling Manual. 
6.3 
Measures to minimize bias: randomization and blinding 
This is an open-label, single-arm study. Therefore, no blinding or randomization is required. 
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6.4 
Treatment compliance 
At each visit after study medication is dispensed, participants must return sharps containers 
containing used syringes or any expired or defective product. Drug accountability must be done 
in the study participant’s presence in order to obtain explanations regarding discrepancies in 
compliance with the dosing regimen. Drug accountability must be recorded on the Drug 
Accountability form. 
If a study participant is found to be persistently noncompliant, the Sponsor, in conjunction with 
the Investigator, will make a decision as to whether the participant should be withdrawn from the 
study. 
Study personnel will assess study medication compliance at every visit to record whether any 
doses were missed. 
If a study participant misses 1 dose (ie, 1 day) of study medication, he/she should take the next 
planned dose as scheduled and the Investigator should be contacted as soon as possible. 
If a study participant misses 2 or more doses, he/she must notify the Investigator immediately 
and the Medical Monitor should be consulted. Ten or more consecutive missed doses will be 
considered a major protocol deviation. 
6.5 
Concomitant medication(s)/treatment(s) 
Concomitant medications include any prescription or over-the-counter medication that is 
ongoing on Day 1 or that is initiated following the first dose of study medication on Day 1. 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
Medications, including over the counter therapeutics, natural products, and vitamins, should not 
be changed during the study, unless medically necessary. 
Participants are expected to remain on stable dose regimens of SOC therapy for gMG throughout 
the Main Treatment Period, including corticosteroids and IST drugs. If during the Extension 
Treatment Period the Investigator determines that dose reduction of SOC therapy for gMG may 
be a reasonable course of action, dose reduction may be initiated, after contacting the Medical 
Monitor. Study participants receiving pyridostigmine treatment may reduce the dose if the 
Investigator identifies intolerable side effects clearly related to pyridostigmine. Prior to altering 
the dose of pyridostigmine, the Investigator should contact the Medical Monitor. Any 
cholinesterase inhibitor, regardless of the dosing regimen, is to be withheld for a minimum of 
10 hours prior to the QMG clinical evaluation (not a requirement for the MG-ADL assessment). 
6.5.2 
Prohibited concomitant treatments (medications and therapies) 
The following concomitant medications are prohibited during the study: 
Absolute contraindications: 
• Aminoglycosides, colomycin, polymyxin, telithromycin, injectable cyclin, macrolides, 
fluoroquinolones 
• Quinines, quinidine, hydroxychloroquine, procainamide 
• Beta-blockers (even in eye drops) 
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• Diphenylhydantoin, trimethadione 
• Dantrolene 
• D-penicillamine 
• Magnesium 
Relative contraindications: 
• Curariform agents: use of nondepolarizing molecules of rapid degradation, such as 
atracurium, is possible but requires precise monitoring 
• Benzodiazepines 
• Neuroleptics (phenothiazine) 
• Carbamazepine 
• Lithium 
IV C5 inhibitor must not be administered while the participant is receiving ZLP. If deemed 
needed as per the Investigator’s judgment, study participant may be readministered their 
previous IV C5 inhibitor or administered a different IV C5 inhibitor after discontinuation of the 
study medication and completion of an EW/Withdrawal Visit. The participant should return for a 
SFU Visit 40 days (±7 days) after the last dose of ZLP. 
6.5.3 
Vaccines 
Administration of live and nonlive vaccines is allowed during the study at the discretion of the 
Investigator and should be documented. This includes administration of nonlive coronavirus 
disease 2019 (COVID-19) vaccines authorized at the time of issuance of this protocol. Current 
medical and scientific evidence does not suggest that there is any medical or scientific reason for 
restricting severe acute respiratory syndrome coronavirus 2 vaccinations in ZLP clinical studies. 
Additionally, given the increased risk for N. meningitidis infection with C5 inhibition or deficit, 
study participants who receive ZLP are required to have documentation of at least 1 dose of 
quadrivalent meningococcal vaccine and meningococcal serotype B vaccine at least 14 days 
prior to the first dose of ZLP if not vaccinated within 3 years prior to the start of study 
medication (Section 5.1). The second dose of the primary vaccination cycle can be administered 
during the study. A booster vaccination should also be administered according to the most 
current relevant guideline (ie, Advisory Committee on Immunization Practices, United States) to 
study participants who have been previously vaccinated against N. meningitidis. 
6.5.4 
Rescue medication 
If rescue therapy becomes necessary due to major deterioration of a study participant’s clinical 
status or risk of MG crisis, as per the Investigator’s judgment, the study participant may receive 
the following rescue medications: 
• IVIG 
• PLEX 
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If such rescue therapy becomes necessary, the choice of IVIG vs PLEX, as well as the frequency 
and duration of such therapy, will be determined by the Investigator. Escalation of doses of 
corticosteroids or IST drugs for rescue is not permitted. 
The Sponsor should be notified immediately upon determination that rescue therapy is necessary 
in any given study participant. A Rescue Therapy Visit should be performed prior to initiation of 
rescue therapy (see Section 1.3 for a list of applicable study procedures). 
If the Investigator, in consultation with the Medical Monitor, considers to be in the best interest 
of the study participant, the study participant will continue ZLP treatment and complete all 
study-specified assessments while undergoing rescue therapy and through the end of the study. 
The date and time of rescue medication administration, the name and dosage regimen of the 
rescue medication, and the reason for initiation of rescue medication must be recorded. 
6.6 
Dose modification 
No dose modifications are allowed during the study. 
6.7 
Criteria for study hold or dosing stoppage 
Not applicable for this study given the safety experience of ZLP from clinical studies. Refer to 
the IB for details. 
6.8 
Treatment after the end of the study 
At the conclusion of the Main Treatment Period, study participants will have the option to 
continue ZLP treatment in the Extension Treatment Period, during which SC ZLP will continue 
to be provided until the approval of the marketing application for the indication of gMG in the 
US or until further notice from the Sponsor. 
If at the end of the Main Treatment Period a study participant chooses not to participate in the 
Extension Treatment Period, the participant will complete an SFU Visit 40 days (±7 days) after 
the last dose of study medication and receive SOC treatment off-study, as recommended by the 
treating physician. 
If during the Extension Treatment Period a study participant discontinues ZLP, he/she will 
transition to SOC treatment off-study as recommended by the treating physician. These 
participants will complete a Withdrawal Visit and a SFU Visit 40 days (±7 days) after the last 
dose of study medication. 
If a participant is in the Extension Treatment Period at the time ZLP becomes commercially 
available, he/she will transition to ZLP treatment outside of the study. He/she will complete a 
Withdrawal Visit and will not need to complete a SFU Visit. If by the time a participant 
completes the Main Treatment Period ZLP is commercially available, the participant may 
transition to commercially available ZLP directly following the Week 12 visit at the end of the 
Main Treatment Period. 
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7 
DISCONTINUATION OF STUDY MEDICATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study medication 
Dosing of a study participant must be immediately and permanently discontinued if: 
• Study participant is diagnosed with meningococcal disease 
• In the opinion of the Investigator and/or Sponsor, it is unsafe for the study participant to 
continue dosing with study medication 
• There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test 
In circumstances where permanent discontinuation from study medication may occur, the 
Investigator is to discuss with the study participant the appropriate processes for discontinuation 
from study medication and further assessments as part of an EW or Withdrawal Visit, followed 
by the SFU Visit. If the study participant does not want to continue the study medication and 
withdraws consent (Section 7.2), the Investigator should contact the Medical Monitor, whenever 
possible, to discuss the withdrawal of a participant in advance. 
7.1.1 
Liver chemistry stopping criteria 
Discontinuation of study medication 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 participant. 
Study medication will be discontinued immediately and permanently for a participant if liver 
chemistry stopping criteria are met. 
Figure 7‒1: Liver chemistry stopping criteria and increased monitoring algorithm 
 
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
≥8xULN
Plus
Symptoms of 
liver injury
or 
hypersensitivity
No
Yes
Yes
Yes
No
No
No
See algorithm 
for continued 
therapy with 
increased liver 
chemistry 
monitoring
Yes
ALT 
≥3xULN 
but 
<8xULN
Yes
Refer to the Liver Safety Required Actions and Follow-up Assessments section in 
Appendix 6. 
Report as an SAE if possible Hy’s Law case: AST/ALT ≥3xULN and Bilirubin 
≥2xULN (>35% direct) or INR>1.5, if measured 
(Note: INR value not applicable to patients on anticoagulants) 
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ALT=alanine aminotransferase; AST=aspartate aminotransferase; INR=international normalized ratio; SAE=serious 
adverse event; ULN=upper limit of normal 
Figure 7‒2: Liver chemistry increased monitoring algorithm with continued study 
intervention for participants with ALT 3xULN but <8xULN 
 
 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; bili=bilirubin; 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 
QTc stopping criteria 
If a clinically significant finding is identified (including, but not limited to changes from 
Baseline in QT interval corrected using Fridericia’s formula [QTcF]) after enrollment, the 
Investigator or qualified designee will determine if the study participant can continue in the study 
and if any change in participant management is needed. This review of the ECG printed at the 
time of collection must be documented. Any new clinically relevant finding should be reported 
as an AE. 
If any of the criteria as listed below based on the ECG reading are met, the ECG will be repeated 
to confirm the finding. In the event that a study participant meets the confirmed criteria, the 
Medical Monitor will be contacted to decide whether the participant will discontinue the study. 
In case the decision is to proceed to discontinuation, an EW/Withdrawal Visit will be performed, 
and the study participant will be required to return to the clinic for a SFU Visit 40±7 days after 
their last dose. The study participant should be referred to a specialist (ie, cardiologist) and 
managed as per local guidance. 
• QTc >500msec OR uncorrected QT >600msec 
Continue Study Treatment   and   Monitor Liver Chemistry
Discontinue Study Treatment 
ALT≥5xULN 
but <8xULN
+ bili <2xULN +
no symptoms
No
➢Must refer to Liver Safety Required Actions and Follow up Assessments section in the Appendix
Yes
ALT ≥3xULN 
but <5xULN
+ bili <2xULN  +
no symptoms
Able to 
monitor  
weekly 
for  ≥2 
weeks
Persists for 
≥2 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
No
No
Able to 
monitor  
weekly 
for  ≥4 
weeks
Persists for 
≥4 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
Yes
ALT ≥5xULN 
ALT <5xULN 
Yes
Yes
Refer to the Liver Safety - Suggested 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 
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• Change from Baseline of QTc >60msec 
For study participants with underlying bundle branch block, follow the discontinuation criteria 
listed below: 
Baseline QTc with Bundle Branch Block 
Discontinuation QTc Threshold with 
Bundle Branch Block 
<450msec 
>500msec 
≥450 to 480msec 
≥530msec 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of treatment 
discontinuation and SFU, and for any further evaluations that need to be completed. 
The study participant should 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. 
If a study participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the Investigator must document this in the site study records. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of study 
discontinuation. 
Participants should be withdrawn from the study if any of the following events occur: 
1. Participant develops an illness that would interfere with his/her continued participation. 
2. Participant is noncompliant with the study procedures or medications in the opinion of the 
Investigator. 
3. Participant restarts administration of previous IV C5 inhibitor or is administered a different 
IV C5 inhibitor (Section 6.5.2). 
4. Participant withdraws his/her consent. 
5. The Sponsor or a regulatory agency requests withdrawal of the participant. 
6. Participant has active suicidal ideation with some intent to act without specific plan, as 
indicated by a positive response (“Yes”) to question 4 of the “Since Last Visit” version of the 
C-SSRS. The participant should be referred immediately to a mental healthcare professional 
and may be withdrawn from the study based upon the Investigator’s judgment of benefit/risk 
of continuing the participant in the study/on study medication. 
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7. Participant has active suicidal ideation with a specific plan as indicated by a positive 
response (“Yes”) to question 5 of the “Since Last Visit” version of the C-SSRS. The 
participant should be referred immediately to a Mental Healthcare Professional and must be 
withdrawn from the study. 
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a study participant in advance. 
If a study participant withdraws from the study, the participant will not be replaced. 
If a study participant withdraws from the study, the participant should immediately stop the 
intake of the study medication and will be required to return to the clinic for an EW/Withdrawal 
Visit (depending on whether the participant withdrew during the Main Treatment Period or 
during the Extension Treatment Period) as soon as possible but no later than the next scheduled 
visit and for a SFU Visit 40±7 days after their last dose of study medication to gather 
information on ongoing AEs and report any new SAEs since the last study visit (Section 1.3). 
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, counsel the participant on the importance of maintaining the assigned visit 
schedule, and ascertain whether or not the participant wishes to and/or should continue in the 
study. 
• Before a study participant is deemed lost to follow up, the Investigator or designee must 
make every effort to regain contact with the participant (at least 1 phone call and 1 written 
message to the participant), and document his/her effort (date and summary of the phone call 
and copy of the written message in the source documents), to complete the final evaluation. 
All results of these evaluations and observations, together with a narrative description of the 
reason(s) for removing the 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). 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence 
or awareness to determine if the participant should continue or discontinue study medication. 
Adherence to the study design requirements, including those specified in 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 study 
participants meet all eligibility criteria. The Investigator will maintain a screening log to record 
details of all study participants screened and to confirm eligibility or record reasons for screening 
failure, as applicable. 
Procedures conducted as part of the study participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICF may be utilized for Screening or Baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in the Schedule of Activities (Section 1.3). 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 500mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
8.1 
Efficacy assessments 
Planned time points for all efficacy assessments are provided in the Schedule of Activities 
(Section 1.3). 
8.1.1 
Clinical efficacy assessments 
Clinical evaluators must be adequately trained prior to conducting any efficacy assessments. 
All self-administered patient-reported outcomes (PROs) (MG-QOL15r, 9-item Treatment 
Satisfaction Questionnaire for Medication [TSQM-9], and Patient Preference assessment) will be 
filled out by the study participant prior to meeting with the physician and prior to dosing or any 
other study procedures. Patient-reported outcomes should be administered in the following order: 
MG-QOL15r, TSQM-9, Patient Preference assessment, and MG-ADL. All remaining clinical 
efficacy assessments should be performed at approximately the same time of day prior to dosing 
(preferably in the morning) and be administered by the same well-trained evaluator (eg, 
neurologist, physical therapist, or other study staff experienced in clinical assessments), where 
applicable, in the same order at each visit throughout the study. 
8.1.1.1 
MG-ADL 
The MG-ADL is a brief 8-item interviewer-administered PRO designed to evaluate MG 
symptom severity. The MG-ADL targets symptoms and disability across ocular, bulbar, 
respiratory, and axial symptoms. Each item is assessed on a 4-point scale, where a score of 0 
represents normal function and a score of 3 represents severely decreased ability to perform that 
function. The total MG-ADL score ranges from 0 to 24, with a higher score indicating more 
disability. A 2-point change in MG-ADL score is considered clinically meaningful (Muppidi et 
al, 2011; Wolfe et al, 1999). 
The MG-ADL assessment will be performed at Screening to assess study participant's eligibility 
and at each study visit (either at the site or over the phone) according to the Schedule of 
Activities (Section 1.3). Detailed instructions regarding the administration of the MG-ADL will 
be provided to sites. 
Minimal Symptom Expression, which is designed to assess how many study participants become 
free or virtually free of MG symptoms as measured by achieving an MG-ADL total score of 0 or 
1 on therapy (Vissing et al, 2020), will be assessed at Week 12. 
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8.1.1.2 
QMG scale 
The QMG is a standardized and validated quantitative strength scoring system that was 
developed specifically for MG. If a study participant is receiving a cholinesterase inhibitor, the 
dose must be withheld for at least 10 hours prior to the assessment. The scale tests 13 items, 
including ocular and facial involvement, swallowing, speech, limb strength, and forced vital 
capacity. Higher scores are representative of more severe impairment. Scoring for each item 
ranges from no weakness (0) to severe weakness (3), with an overall score range from 0 to 39. A 
change in the QMG score of 3 points or more may be considered clinically meaningful in a 
typical clinical study population of patients with MG (Katzberg et al, 2014; Barohn et al, 1998). 
8.1.1.3 
MG-QOL15r 
The MG-QOL15r is a 15-item self-administered PRO that was designed to assess quality of life 
in patients with MG. Each item is scored on a 0 to 2-point scale (0=Not much at all, 
1=Somewhat, 2=Very much). The total score is the sum of the 15 individual item scores, ranging 
from 0 to 30. Higher scores indicate more severe impact of the disease on aspects of the patient’s 
life (Burns et al, 2016; Burns et al, 2010). 
8.1.1.4 
Myasthenia Gravis Foundation of America Post-Intervention Status 
The Myasthenia Gravis Foundation of America Post-Intervention Status is a 
physician-determined assessment of clinical symptoms of MG after initiation of MG-specific 
therapy. Minimal Manifestation is defined as follows: 
“The patient has no symptoms of functional limitations from MG but has some weakness on 
examination of some muscles. This class recognizes that some patients who otherwise meet the 
definition of Complete Stable Remission or Pharmacologic Remission do have weakness that is 
only detectable by careful examination.” 
For the purpose of the current study, Minimal Manifestation will be determined at Week 12, the 
EW Visit, or a Rescue Therapy Visit (rather than after 1 year). Change in status (improved, 
unchanged, worse, exacerbation, or died) of MG will also be determined. 
8.1.1.5 
TSQM-9 
The TSQM-9 is a self-administered PRO with Likert-type response options that assesses 
satisfaction with medication use over 3 domains: Effectiveness (items 1 through 3), Convenience 
(items 4 through 6), and Global Satisfaction (items 7 through 9). Each domain score ranges from 
0 to 100, with higher scores indicating increased satisfaction. See TSQM user manual version 1.1 
for instructions on calculation of scores. The instrument is not disease specific. The TSQM-9 and 
previous versions have undergone qualitative and psychometric testing and were found to be 
valid and reliable (Regnault et al, 2012; Bharmal et al, 2009; Atkinson et al, 2005; Atkinson et 
al, 2004). 
8.1.1.6 
Patient Preference assessment 
The Patient Preference assessment is a self-administered PRO. A single question will be asked at 
the end of the Main Treatment Period and the EW/Withdrawal Visits, assessing the study 
participant’s preference for treatment: 
“Think about your experience of the subcutaneous treatment you received during the clinical trial 
compared with your previous intravenous treatment. 
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All things considered, which treatment did you prefer? (please select one answer) 
• Intravenous infusion 
• Subcutaneous injection 
• No preference” 
Given the limitations of the study design, this question/assessment will not produce robust and 
generalizable patient preference data, but it will generate exploratory data into patient 
preferences based on this sample’s experience with the 2 treatments. To generate robust patient 
preference evidence within a clinical study, a cross-over study design is typically used. 
8.1.1.7 
Time needed for administration of SC ZLP 
The time it takes for study participants to administer SC ZLP will be recorded (ie, the time it 
takes for the dose to be delivered into the skin/body). The time needed for administration of SC 
ZLP will be assessed by site staff using a stopwatch to record the time needed for study 
participants to complete the administration. Timing using the stopwatch will start at removal of 
the pre-filled syringe needle cap and will stop when the syringe is completely removed from the 
skin. 
8.1.1.8 
Time to first receipt of rescue therapy 
The date of the first receipt of rescue therapy during the 12-week Main Treatment Period will be 
recorded. 
8.1.1.9 
Change in SOC therapy dose regimen 
Any changes to SOC therapy that occur during the study will be recorded. 
8.1.2 
Pharmacodynamics 
Blood sampling for PD analysis of complement activation will be performed as specified in the 
Schedule of Activities (Section 1.3). Blood samples for PD analyses will be obtained prior to 
dosing (within 1 hour of dosing). Instructions for the collection and handling of biological 
samples will be provided by UCB. The actual date and time (24-hour clock time) of each sample 
will be recorded. 
The sheep red blood cell lysis assay will be used to evaluate classical complement pathway 
activation. 
All back-up samples already planned for collection will be stored for all participants in this study 
to support potential future exploratory biomarker research, which could include, but is not 
limited to the evaluation of biomarkers relative to disease biology and progression, study 
medication treatment and response, and/or mechanism of action of the study medication 
treatment. 
8.2 
Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). 
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8.2.1 
Physical examination 
A complete physical examination will include, at a minimum, abdomen; cardiac; general 
appearance; eyes, ear, nose, and throat; head and neck; musculoskeletal; neurological; 
respiratory; and skin/mucosal. Height and weight will also be measured and recorded. Height 
will only be measured at Screening. 
  
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Clinically relevant findings or worsening of previous findings will be recorded as AEs. 
8.2.2 
Vital signs 
Temperature, pulse rate, respiratory rate, and blood pressure will be assessed. 
Blood pressure and pulse measurements will be assessed in the sitting position with a completely 
automated device. Manual techniques will be used only if an automated device is not available. 
Blood pressure measurements should preferably be made using the nondominant arm, and the 
same measurement technique should be used throughout the study for the same participants. 
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). 
8.2.3 
Electrocardiogram 
A 12-lead ECG will be obtained as outlined in the Schedule of Activities (see Section 1.3) using 
an ECG machine that automatically measures the heart rate and measures PR, QRS, QT, and 
QTc intervals. Refer to Section 7 for QTc withdrawal criteria and any additional QTc readings 
that may be necessary. 
All ECG recordings should be taken with the study participant resting in the supine position for 
at least 5 minutes before the recording.  
8.2.4 
Clinical safety laboratory assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and 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. 
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 
(Section 1.3). 
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If laboratory values from nonprotocol specified laboratory assessments performed at the 
institution’s local 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 eCRF. 
8.2.5 
Suicidal risk monitoring 
Study participants being treated with ZLP should be monitored appropriately and observed 
closely for suicidal ideation and behavior or any other unusual changes in behavior. 
Families and caregivers of study participants being treated with ZLP should be instructed to 
monitor 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 (Posner et al, 2011; 
Mundt et al, 2010). The “Screening/Baseline” version of the C-SSRS will be completed during 
the Screening Visit and the “Since Last Visit” version will be completed at all other time points 
detailed in the Schedule of Activities (Section 1.3). Criteria for participant withdrawal based on 
response to the C-SSRS and Investigator’s judgment are defined in Section 7.2. 
8.3 
AEs and SAEs 
The definitions of an AE and SAE can be found in Appendix 3 (Section 10.3). 
Adverse events will be reported by the study participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study medication or study procedures, or that caused 
the participant to discontinue the study medication or the study (see Section 7). 
For results disclosure on public registries (eg, ClinicalTrials.gov), treatment-emergent adverse 
events (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 study participant 
completes the study (Section 4.4). Collection of AEs and SAEs will be done 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 eCRF even if no study medication was taken but specific study 
procedures were conducted. This includes all AEs not present prior to the Screening Visit and all 
AEs that recurred or worsened after the Screening 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 
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medication), up to 40 days from the end of the study for each participant, and to also inform 
participants of the need to inform the Investigator of any SAE within this period. Serious AEs 
that the Investigator thinks may be associated with the study medication must be reported to 
UCB regardless of the time between the event and the end of the study. 
The method of recording, evaluating, and assessing causality of AEs and SAEs 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 
nonleading 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 nonserious AEs of special interest (as 
defined in Section 8.3.6), will be followed until resolution, stabilization, the Investigator 
determines that it is no longer clinically significant, the event is otherwise explained, or the 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 medication 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 medication under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB), and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and Sponsor policy and forwarded to Investigators as 
necessary. 
An Investigator who receives an Investigator safety report describing 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 IRB, if appropriate according to local requirements. 
8.3.5 
Pregnancy 
Details of all pregnancies in female study participants and female partners of male study 
participants who become pregnant will be collected after the start of study medication and until 
40 days after the last dose of study medication. 
If a pregnancy is reported, the Investigator must immediately inform the Sponsor within 
1 working day of learning of the pregnancy and should follow the procedures outlined in 
Appendix 4 (Section 10.4). 
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The participant should discontinue study medication as soon as pregnancy is known (by positive 
pregnancy test), and the following should be completed: 
• The participant should return for an EW/Withdrawal Visit. 
• An SFU Visit should be scheduled 40±7 days after the 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 is any AE that a regulatory authority has mandated to be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound. 
For ZLP, 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 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. 
8.3.7 
Monitoring of infection 
To mitigate the risk of infection, study participants will be counseled and reminded of the early 
signs and symptoms of Neisseria meningitidis infection. A patient safety card detailing the signs 
and symptoms of infection, with instructions to seek immediate medical attention if any such 
symptoms occur, will be provided to each study participant. 
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 IRBs 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. 
As appropriate for the stage of development and accumulated experience with the study 
medication, medically qualified personnel at UCB may identify additional safety measures for 
which data will be periodically reviewed during the study. 
8.5 
Treatment of overdose 
For this study, any dose of ZLP greater than the intended daily dose will be considered an 
overdose. Overdose events are only considered AEs or SAEs if there are associated clinical signs 
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and symptoms, or if the act of taking the excess study medication itself is an AE or SAE (eg, 
suicide attempt). 
It is not anticipated that overdose of ZLP will lead to acute or specific systemic TEAEs. In case 
of overdose, clinically appropriate supportive measures should be instituted as determined by the 
clinical scenario and in consultation with the Medical Monitor. 
In the event of an overdose, the Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the study participant for any AE/SAE and laboratory abnormalities. 
3. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the study participant. 
8.6 
Pharmacokinetics 
Blood samples of approximately 2mL will be collected for measurement of plasma 
concentrations of ZLP and its major metabolites 
 as specified in the 
Schedule of Activities (Section 1.3). Blood samples for PK analyses will be obtained prior to 
dosing (within 1 hour of dosing). Instructions for the collection and handling of biological 
samples will be provided by UCB. The actual date and time (24-hour clock time) of each sample 
will be recorded. 
For local Rescue Therapy Visits only, blood samples for PK analysis will be collected within 
1 hour prior to administration of each round of rescue therapy. If a study participant receives 
PLEX treatment as rescue therapy, PK will be measured in the exchanged plasma. If rescue 
therapy is administered at a location separate from the clinical site, then there is no need to 
collect blood samples for PK. 
Samples will be used to evaluate the PK of ZLP and its metabolites. Samples collected for PK 
analyses of ZLP and metabolite plasma concentration may also be used to evaluate safety or 
efficacy aspects related to concerns arising during or after the study. 
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the Sponsor 
and site study files, but will not constitute a protocol amendment. The IRB will be informed of 
any safety issues that require alteration of the safety monitoring scheme or amendment of the 
ICF. 
All back-up samples already planned for collection will be stored for all participants in this study 
to support potential future exploratory biomarker research, which could include, but is not 
limited to the evaluation of biomarkers relative to disease biology and progression, study 
medication treatment and response, and/or mechanism of action of the study medication 
treatment. 
8.7 
Immunogenicity assessments 
Immunogenicity is not evaluated in this study. 
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8.8 
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 are the defined analysis sets: 
• Enrolled Set (ES): The ES will include all study participants who signed the ICF. 
• Intention-to-Treat (ITT) Population: The ITT Population will include all eligible study 
participants. Efficacy analyses will be performed on the ITT in case there is a difference of at 
least 5 participants as compared to the modified Intention-to-Treat (mITT) Population. 
• Modified ITT Population: The mITT Population will include all eligible study participants 
who received at least 1 post-Baseline dose of study medication and had at least 
1 post-Baseline assessment. The mITT Population will be used for all efficacy analyses. 
• Safety Set (SS): The SS will include all study participants who received at least 1 dose of 
study medication and will be used for the demography and safety analyses. 
• Pharmacokinetic Per-Protocol Set (PK-PPS): The PK-PPS will include all study participants 
in the safety population who received at least 1 dose of study medication and had at least 
1 quantifiable PK measurement postdose of study medication without important protocol 
deviations that would affect the PK. The PK-PPS will be used for all PK analyses. 
• Pharmacodynamic Per-Protocol Set (PD-PPS): The PD-PPS will include all study 
participants in the safety population who received at least 1 dose of study medication and had 
at least 1 quantifiable PD measurement postdose of study medication without important 
protocol deviations that would affect the PD. The PD-PPS will be used for all PD analyses. 
Additional detail about analysis sets will be provided in the SAP. 
9.2 
General statistical considerations 
Statistical analysis and generation of tables, figures, and study participant data listings will be 
performed using statistical analysis system (SAS®, SAS Institute, Cary, NC, US) Version 9.4 or 
higher using validated program code according to relevant SOP. 
For continuous parameters, descriptive statistics will include the number of study participants, 
arithmetic mean, standard deviation (SD), median, minimum, and maximum (with 25th and 75th 
percentiles as optional). For categorical parameters, the number and percentage of study 
participants in each category will be presented. 
For ZLP plasma concentration, the geometric mean and corresponding coefficient of variation 
(CV) will be presented. 
Baseline is defined as the last nonmissing measurement collected before the first injection. 
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9.3 
Planned efficacy/outcome analyses 
9.3.1 
Secondary efficacy estimand/secondary endpoint analyses 
For the efficacy endpoint, CFB to Week 12 in MG-ADL score, a one-sample t-test will be used 
to compare the mean CFB to Week 12 in MG-ADL score to a noninferiority (NI) margin. The NI 
margin being investigated is a clinically relevant 2-point increase (worsening) at Week 12. The 
Week 12 CFB will be compared to 2 at a 1-sided α=0.025 level for the mITT Population. 
Additional supplementary analyses and sensitivity analyses for the secondary efficacy estimand 
will be provided in the SAP. 
The additional secondary efficacy endpoint (CFB to Week 12 in QMG score) will be analyzed 
following the estimand structure defined for the MG-ADL score (Section 3.1). These analyses 
will be descriptive. 
9.3.2 
Other efficacy endpoint analyses 
The other efficacy endpoints analyses will be descriptive. Additional information about these 
analyses will be provided in the SAP. 
9.4 
Planned safety and other analyses 
9.4.1 
Safety analyses 
Safety analyses will be performed on the Safety Set. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities. A TEAE is 
defined as any event that was not present prior to the first administration of study medication or 
any unresolved event already present before the first administration of study medication that 
worsens in intensity following exposure to treatment. Incidence rates for TEAEs will be 
summarized overall, by maximum severity, and by relationship to study medication. Serious AEs 
will also be summarized. 
Laboratory evaluations, physical examinations, and ECG will be presented in listings and 
summarized over time. In this study, the clinical laboratory, physical examination, and ECG 
assessments conducted at Screening will be considered the baseline values for evaluating of the 
other safety endpoints. 
A by-participant listing of the C-SSRS questionnaire data will be provided. 
9.4.2 
Other analyses 
Individual PK results will be presented in listings and summarized using descriptive statistics. 
Pharmacodynamic endpoints will be presented in listings and summarized at each scheduled 
assessment time point. 
9.5 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol which could potentially have a 
meaningful impact on study conduct or on the key safety, efficacy, or other outcomes for an 
individual study participant. The criteria for identifying important protocol deviations and the 
classification of important protocol deviations will be defined within the Important Protocol 
Deviations Template. To the extent feasible, rules for identifying protocol deviations will be 
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defined without review of the data and without consideration of the frequency of occurrence of 
such deviations. Whenever possible, criteria for identifying important protocol deviations will be 
implemented algorithmically to ensure consistency in the classification of important protocol 
deviations across all study participants. 
All important protocol deviations will be listed by study participant. 
A listing of all important protocol deviations related to the COVID-19 pandemic will be 
provided. Additionally, this listing will be repeated by during and post- the COVID-19 pandemic 
(in case the pandemic ends before the study is complete) based on the deviation start dates 
relative to the pandemic cutoff dates. 
9.6 
Handling of dropouts or missing data 
For secondary efficacy analyses, missing data will be handled according to the secondary 
efficacy estimand definition: 
• For missing data of participants who discontinue from the study, a missing at random 
assumption will be used for imputation. This is in relation to the assumption that the 
participant had remained on their treatment throughout the study. 
• For other missing data, the same missing at random assumption as the one used for imputing 
missing data of participants who discontinue from the study will be applied. 
Missing or partial dates for safety evaluations will be imputed and full details of these algorithms 
will be presented in the SAP. Baseline is defined as the last nonmissing pretreatment 
measurement (Section 9.2). Therefore, data from the Screening Visit (if available) will be used 
as Baseline values if data are missing at Day 1. 
No further imputations of any other missing data are planned. 
9.7 
Planned interim analysis and data monitoring 
If ZLP is not commercially available in the US at the time of the last visit of the last participant 
in the Main Treatment Period, an interim analysis will be conducted. This interim analysis will 
include all data collected during the Main Treatment Period. 
9.8 
Determination of sample size 
The secondary efficacy estimand will investigate if the Week 12 MG-ADL score is noninferior 
to the Baseline MG-ADL score with an NI margin of 2. It is assumed that the Week 12 CFB has 
an SD of 3 and that the true CFB is 0. Given a sample size of 20 study participants, the study has 
approximately 80% power to detect this, based on a 1-sided alpha of 0.025. 
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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
The study will be conducted under the auspices of an IRB, as defined in local regulations, 
International Council for Harmonisation (ICH)-Good Clinical Practice (GCP), and in accordance 
with the ethical principles that have their origin in the Declaration of Helsinki. 
The Investigator/UCB will ensure that an appropriately constituted IRB that complies with the 
requirements of the current ICH-GCP version or applicable country-specific regulations will be 
responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, ICF, IB, 
Investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all other 
participant-related documents to be used for the study to the IRB for its review and approval. 
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB for the protocol. 
The Investigator will also promptly report to the IRB 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 IRB 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 IRB as 
allowed. 
As part of the IRB requirements for continuing review of approved studies, the Investigator will 
be responsible for submitting periodic progress reports to the IRB (based on IRB 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 IRB following study completion. 
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
The appropriate IRB will also be informed by the Investigator or the Sponsor, as specified by the 
applicable regulatory requirements. Where applicable, Investigators are to provide the Sponsor 
(or its representative) with evidence of such IRB 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 contract research organization 
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 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, or his/her legal representative, 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, IRB 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 IRB and use of the amended form. 
All studies conducted at centers in the US must include the use of a Health Insurance Portability 
and Accountability Act authorization form. 
The participant may withdraw his/her consent to participate in the study at any time. A 
participant is considered as enrolled in the study when he/she has signed the ICF. An eCRF must 
not be started, nor may any study specific procedure be performed for a given participant, 
without having obtained his/her written consent to participate in the study. 
10.1.4 
Data protection 
UCB staff (or designee) will affirm and uphold the study participant’s confidentiality. 
Throughout this study, all data forwarded to UCB (or designee) will be identified only by the 
participant number assigned at Screening. 
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB, or representatives of regulatory authorities will be allowed to review that portion of the 
participant’s primary medical records that directly concerns this study (including, but not limited 
to, laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a participant’s study participation, and autopsy reports for deaths 
occurring during the study). 
The 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 IRB members, and by inspectors from regulatory authorities. 
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10.1.5 
Committees structure 
Not applicable. 
10.1.6 
Data quality assurance 
All 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 eCRF. 
The Investigator must permit study-related monitoring, audits, IRB review, and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, legible, contemporaneous, original, and 
attributable from source documents; that the safety and rights of 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 will be established for the study using parameters related to patient 
safety reporting and reliability of study results. The parameters will be monitored throughout the 
study to identify systematic issues. Parameters used, parameter values, important deviations from 
the quality tolerance limits, and actions taken will be summarized in the clinical study report. 
10.1.6.1 
Case report form completion 
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
eCRFs and in all required reports. 
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change. 
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator. 
The Investigator should maintain a list of personnel authorized to enter data into the eCRF. 
Detailed instructions will be provided in the eCRF Completion Guidelines. 
10.1.6.2 
Apps 
Not applicable. 
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10.1.7 
Source documents 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies and/or printouts of eCRFs are not considered 
acceptable source documents. 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, quality of life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area. 
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the Investigator and become a permanent part of the 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. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB 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. 
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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. 
• Local laboratory results are only required in the event that the central laboratory results are 
not available in time for either study medication administration and/or response evaluation. If 
a local sample is required, it is important that the sample for central analysis is obtained at 
the same time. Additionally, if the local laboratory results are used to make either a study 
medication decision or response evaluation, the results must be entered into the eCRF. 
• The use of local laboratory results may be considered, if necessary, after consultation with 
the appropriate Sponsor representative (eg, Clinical Project Manager or Study Physician). 
• 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. 
Table 10‒1: Protocol-required safety laboratory assessments 
Laboratory 
assessments 
Parameters 
Hematology 
Platelet count 
RBC indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with 
differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC count 
Hemoglobin 
Hematocrit 
Clinical 
chemistry a 
BUN 
Potassium 
AST/SGOT 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
ALT/SGPT 
Total protein 
 
Glucose 
Calcium 
Alkaline phosphatase 
Amylase 
 
Lipase 
 
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 women of 
non-childbearing potential only) 
• 
Serum hCG pregnancy test (as needed for women of childbearing potential) b 
The results of each test must be entered into the eCRF. 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; eCRF=electronic 
Case Report form; HBsAg=hepatitis B surface antigen; hCG=human chorionic gonadotropin; 
INR=international normalized ratio; IRB=Institutional Review Board; MCH=mean corpuscular hemoglobin; 
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Table 10‒1: Protocol-required safety laboratory assessments 
Laboratory 
assessments 
Parameters 
MCV=mean corpuscular volume; RBC=red blood cell; SAE=serious adverse event; SGOT=serum glutamic-
oxaloacetic transaminase; SGPT=serum glutamic-pyruvic transaminase; ULN=upper limit of normal; 
WBC=white blood cell 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1.1 and Appendix 6 (Section 10.6). All events of ALT ≥3×ULN and 
bilirubin ≥2×ULN (>35% direct bilirubin) or ALT ≥3×ULN and INR >1.5, if INR measured, may indicate 
severe liver injury (possible Hy’s Law) and must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis). 
b Local urine pregnancy testing will be performed at visits subsequent to the Screening Visit. 
Investigators must document their review of each laboratory safety report. 
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10.3 
Appendix 3: Adverse events – Definitions and procedures for 
recording, evaluating, follow up, and reporting 
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 an 
AE or SAE if they fulfil the definition of an AE or SAE. 
 
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Events NOT meeting the AE definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the Investigator to be more 
severe than expected for the study participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the study participant’s 
condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
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Definition of SAE 
If an event is not an AE per definition above, then it cannot be a SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 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 eCRF. 
• 
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 eCRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to UCB. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the 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 a SAE, NOT when it is rated as severe (eg, a severe AE may be 
either serious or not serious, depending on whether these criteria are also met). 
The National Cancer Institute Common Terminology Criteria for Adverse Events should be used as a 
supportive standardization instrument to evaluate AEs and SAEs but the final intensity grading by the 
Investigator must be mild, moderate, or severe. 
 
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Assessment of causality 
• 
The Investigator is obligated to assess the relationship between study medication and each 
occurrence of each AE/SAE. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study medication administration will be 
considered and investigated. 
• 
The Investigator will also consult the 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 participant dies during participation in the study or during a recognized follow-up period, 
the Investigator will provide UCB with a copy of any post-mortem findings including 
histopathology. 
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The Investigator will submit any updated SAE data to UCB within 24 hours of receipt of the 
information. 
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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 
offline 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 offline, then 
the site can report this information on a paper SAE form (see next section) or to the UCB 
Study Physician/Medical Monitor 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 the UCB Study Physician/Medical Monitor. 
• 
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 nonestrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception guidance 
Male participants 
For male participants with female partners of childbearing potential it is recommended that they 
agree to ONE of the following during the study and for at least 40 days after the last dose of 
study medication: 
• Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent 
on a long-term and persistent basis) and agree to remain abstinent. 
• Agree to use a male condom when having penile-vaginal intercourse with a woman of 
childbearing potential who is not currently pregnant. 
In addition, male participants are recommended to refrain from donating sperm for the duration 
of the study and for 40 days after the last dose of study medication. 
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Male participants with a pregnant or breastfeeding partner are recommended to remain abstinent 
from penile-vaginal intercourse or use a male condom during each episode of penile penetration 
during the study and for at least 40 days after the last dose of study medication. 
Female participants 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in Table 10‒2, 
during the study and for at least 40 days after the last dose of study medication. 
Table 10‒2: Highly effective contraceptive methodsa 
Highly effective contraceptive methods that are user dependentb 
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen and 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 
• 
IUD 
• 
IUS 
• 
Bilateral tubal occlusion 
Vasectomized partner 
Vasectomy 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 participant. 
IMP=investigational medicinal product; IUD=intrauterine device; IUS=intrauterine hormone-releasing system; 
WOCBP=woman of child-bearing potential 
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 to when 
these newly started methods would become effective. 
b Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with 
local regulations regarding the use of contraceptive methods for participants participating in clinical studies. 
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Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test. 
• Additional pregnancy testing will be performed as described in the Schedule of Activities 
(Section 1.3). 
• 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. 
Male participants with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This applies 
only to male participants who receive study medication. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 1 working day of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the Sponsor. Generally, the follow 
up will be at least 12 months after the delivery date. Any termination of the pregnancy will 
be reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
Female participants who become pregnant 
• Any female participant who becomes pregnant while participating in the study will be 
withdrawn from study medication. 
• The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 1 working day of learning of a participant's 
pregnancy. The participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the participant and the neonate, and the 
information will be forwarded to the Sponsor. Generally, the follow up will be at least 
12 months after the delivery date. Any termination of pregnancy will be reported, regardless 
of fetal status (presence or absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be a SAE and will be reported as such. Any poststudy 
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. 
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10.5 
Appendix 5: Genetics 
Not applicable. 
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10.6 
Appendix 6: Liver safety – suggested actions and follow-up 
assessments 
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 participant withdrawal (if applicable), 
must be recorded in the source documents. The eCRF must document the primary reason for 
discontinuation of study medication. 
A specific monitoring plan must be agreed between the UCB Study Physician and the 
Investigator for study participants who have ALT >5 ULN. The monitoring plan should include 
any necessary follow-up assessments (until resolution of the abnormal laboratory values). 
Phase 3-4 liver chemistry stopping criteria are designed to assure study participant safety and to 
evaluate liver event etiology. 
Liver chemistry stopping criteria and follow-up assessments are presented in Table 10‒3. 
Table 10‒3: Liver chemistry stopping criteria and follow-up assessments 
Liver chemistry stopping criteria 
ALT-absolute 
ALT 8x ULN 
ALT Increase 
ALT 5xULN but <8xULN persists for 2 weeks 
ALT 3xULN but <5xULN 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 5xULN but <8xULN and cannot be monitored weekly for 2 weeks 
ALT 3xULN but <5xULN 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 eCRF, and complete 
an SAE data collection tool if the event also 
met the criteria for an SAEb 
• 
Viral hepatitis serologyd 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward trend 
• 
Only in those with underlying chronic 
hepatitis B at study entry (identified by 
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Table 10‒3: Liver chemistry stopping criteria and follow-up assessments 
Liver chemistry stopping criteria 
• 
Perform liver chemistry follow-up assessments 
• 
Monitor the participant until liver chemistry test 
abnormalities resolve, stabilize, or return to 
baseline (see MONITORING) 
• 
Do not restart/rechallenge participant with 
study medication unless allowed per protocol 
and UCB approval is granted 
• 
If restart/rechallenge is not allowed per 
protocol or not granted, permanently 
discontinue study medication, and continue 
participant in the study for any 
protocol-specified follow-up assessments 
• 
Consider the need for a toxicology screening 
 
MONITORING: 
For bilirubin or INR criteria 
• 
Repeat liver chemistry tests (include ALT, 
AST, ALP, bilirubin) and perform liver event 
follow-up assessments within 24 hours 
• 
Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, stabilize, 
or return to baseline 
• 
A specialist or hepatology consultation is 
recommended 
For all other criteria 
• 
Repeat liver chemistry tests (include ALT, 
AST, ALP, bilirubin) and perform liver 
chemistry follow-up assessments within 24 to 
72 hours 
• 
Monitor participants weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to baseline 
positive HBsAg): quantitative hepatitis B 
DNA and hepatitis delta antibodye 
• 
Obtain blood sample for PK analysis at the 
earliest time point following confirmation of 
a liver eventf 
• 
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, 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 
For bilirubin or INR criteria: 
• 
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 participants 
with definite or likely acetaminophen use in 
the preceding week [James et al, 2009]) 
NOTE: Not required in China 
• 
Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver disease; 
complete liver imaging and/or liver biopsy 
eCRFs 
AE=adverse event; ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
CPK=creatine phosphokinase; eCRF=electronic 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; PCR=polymerase 
chain reaction; PK=pharmacokinetic; SAE=serious adverse event; ULN=upper limit of normal 
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Table 10‒3: Liver chemistry stopping criteria and follow-up assessments 
Liver chemistry stopping criteria 
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 
serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable urinary bilirubin 
on dipstick which is indicative of direct bilirubin elevations suggesting liver injury. 
b All events of ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin) or ALT ≥3xULN and INR >1.5 may 
indicate severe liver injury (possible ‘Hy’s Law’) and must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis). The INR measurement is not required and the stated threshold value will not apply to 
participants receiving anticoagulants. 
c 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 If hepatitis delta antibody assay cannot be performed, it can be replaced with a PCR of hepatitis delta RNA 
virus (where needed) (Le Gal et al, 2005). 
f Record the date/time of the PK blood sample draw and the date/time of the dose of study medication prior to the 
PK blood sample draw on the eCRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are 
in the Laboratory Manual. 
Liver chemistry increased monitoring criteria with continued study medication are presented in 
Table 10‒4. 
Table 10‒4: Liver chemistry increased monitoring criteria with continued study 
medication 
Liver chemistry increased monitoring criteria 
Criteria 
Actions 
ALT 5xULN and <8xULN and bilirubin 
<2xULN without symptoms believed to 
be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 2 weeks. 
OR 
ALT 3xULN and <5xULN and bilirubin 
<2xULN without symptoms believed to 
be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 4 weeks. 
• 
Notify the UCB Medical Monitor within 24 hours of 
learning of the abnormality to discuss participant 
safety. 
• 
Participant can continue study medication. 
• 
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 participant meets liver chemistry 
stopping criteria, proceed as described in 
Section 7.1.1. 
• 
If ALT decreases from ALT 5xULN and <8xULN to 
≥3xULN but <5xULN, continue to monitor liver 
chemistries weekly. 
• 
If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor participants twice monthly 
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Table 10‒4: Liver chemistry increased monitoring criteria with continued study 
medication 
Liver chemistry increased monitoring criteria 
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 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BMI 
body mass index 
C5 
complement component 5 
CFB 
change from Baseline 
COVID-19 
coronavirus disease 2019 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CV 
coefficient of variation 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ES 
Enrolled Set 
EW 
Early Withdrawal 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
gMG 
generalized myasthenia gravis 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed Consent form 
ICH 
International Council for Harmonisation 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IST 
immunosuppressant therapy 
ITT 
Intention-to-Treat 
IV 
intravenous 
IVIG 
intravenous immunoglobulin G 
MG 
myasthenia gravis 
MG-ADL 
Myasthenia Gravis-Activities of Daily Living 
MGC 
Myasthenia Gravis Composite 
MGFA 
Myasthenia Gravis Foundation of America 
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MG-QOL15r 
Myasthenia Gravis-Quality of Life Revised 
mITT 
Modified Intention-to-Treat 
NI 
noninferiority 
PD 
pharmacodynamic(s) 
PDILI 
potential drug-induced liver injury 
PD-PPS 
Pharmacodynamic Per-Protocol Set 
PK 
pharmacokinetic(s) 
PK-PPS 
Pharmacokinetic Per-Protocol Set 
PLEX 
plasma exchange 
PRO 
patient-reported outcome 
QMG 
Quantitative Myasthenia Gravis 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
SD 
standard deviation 
SFU 
Safety Follow-up 
SOC 
standard of care 
SOP 
standard operating procedure 
SS 
Safety Set 
TEAE 
treatment-emergent adverse event 
TSQM-9 
9-item Treatment Satisfaction Questionnaire for Medication 
ULN 
upper limit of normal 
WOCBP 
woman of childbearing potential 
ZLP 
zilucoplan 
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10.11 
Appendix 11: Protocol amendment history 
Amendment 1 (15 Jul 2022) 
Overall Rationale for the Amendment: 
The protocol amendment was considered necessary to remove the requirement for the collection 
of blood samples for exploratory biomarkers, and to add that back-up samples may be retained 
for future exploratory biomarker analysis. Additional changes include the following: clarified 
that screening clinical laboratory and physical examination assessments will be considered the 
baseline values for evaluating the other safety endpoints; removed the requirement for brief 
physical examinations, and electronic version of the C-SSRS scale; and amended the 
contraception guidance. The table below does not include correction of minor typographical 
errors and formatting/stylistic changes. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1, Synopsis, 
Table 1-1 
-Added ECG to other safety endpoints  
 
-Added footnote “a” to clarify that the 
clinical laboratory, physical 
examination, and ECG assessments 
conducted at screening will be 
considered the baseline values for 
evaluating the other safety endpoints. 
-Added for the evaluation of 
updated corrected QT 
interval (QTc) stopping 
criteria 
-As clinical laboratory, 
physical examination, and 
ECG assessments are not 
performed at the Baseline 
Visit in this study, footnote 
“a” was added to clarify and 
confirm that the respective 
screening assessments will be 
considered as baseline when 
evaluating the other safety 
endpoints. 
Section 1.3, Schedule of 
Activities, Table 1-2 
-Removed brief physical examination 
and footnote “n”, regarding brief 
physical examination at the Baseline 
Visit. 
-Removed in order to have a 
consistent approach to all 
study participants, and to 
reduce study complexity and 
patient burden. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3, Schedule of 
Activities, Table 1-2 
-Removed requirement for blood 
sampling for exploratory biomarker 
analyses. 
-Added to footnote “u” that back-up 
specimens may be retained for future 
exploratory biomarker analyses. 
 
 
 
-Added ECG assessment to Screening 
Visit, at Week 2, Week 12, Early 
Withdrawal, and Safety Follow-up 
visits. 
 
 
 
-Remove footnote “n” saying that vital 
signs will be assessed at all complete 
and brief physical examination. 
 
 
-Added footnote “n” to specify that 
clinical laboratory, physical 
examination, and ECG assessments 
conducted at Screening will be 
considered the baseline values for 
evaluating of the other safety endpoints. 
 
-Collection of additional 
specimens is no longer 
necessary because the 
exploratory biomarker 
specimen analyses could be 
performed with the existing 
back-up specimens, which 
are collected as part of the 
pharmacokinetic/ 
pharmacodynamic analyses. 
-ECG added to evaluate QTc 
criteria to determine 
eligibility (see exclusion 
criteria #11) and added to 
safety assessments to 
evaluate QTc stopping 
criteria. 
-Timepoints for vital signs 
evaluations are shown in 
Table 1-2 and there is need to 
add a footnote to specify 
these timepoints. 
-As clinical laboratory, 
physical examination, and 
ECG assessments are not 
performed at the Baseline 
Visit in this study, footnote 
“n” was added to clarify and 
confirm that the respective 
screening assessments will be 
considered as baseline when 
evaluating the other safety 
endpoints. 
Section 3, Table 3-1 
-Added ECG to other safety endpoints.  
 
-Added footnote “a” to clarify that the 
clinical laboratory, physical 
examination, and ECG assessments 
conducted at screening will be 
considered the baseline values for 
evaluating the other safety endpoints. 
-Added for the evaluation of 
updated QTc stopping 
criteria. 
-As clinical laboratory, 
physical examination, and 
ECG assessments are not 
performed at the Baseline 
Visit in this study, footnote 
“a” was added to clarify and 
confirm that the respective 
screening assessments will be 
considered as baseline when 
evaluating the other safety 
endpoints. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 5.2 Exclusion 
criteria 
The following exclusion criteria #11 
was added: 
QTc interval >450msec for male 
participants, QTc >470msec for female 
participants, or QTc >480 msec in 
participants with bundle branch block. 
NOTE: The QTc is the QT interval 
corrected for heart rate according to 
Fridericia's formula (QTcF). It is either 
machine read or manually overread.  
QTc should serve as a criteria 
to determine eligibility for an 
individual participant prior to 
initiation of the study. 
Section 6.1 Treatments 
administered 
Changed treatment type from 
“Biologic” to “Drug” in Table 6-1 
Treatment administered. 
Correction of classification 
error. 
Section 7.1.2 QTc stopping 
criteria 
Updated QTc stopping criteria. 
QTc stopping criteria updated 
to provide more specific 
stopping criteria. 
Section 8.1.2, 
Pharmacodynamics 
Section 8.6, 
Pharmacokinetics 
Added that back-up samples already 
planned for collection will be stored for 
all participants in this study to support 
potential future exploratory biomarker 
research. 
The addition of the text is 
to clarify that the collected 
samples for PK and PD 
can be used for future 
exploratory analysis as the 
stand-alone exploratory 
biomarker samples have 
been removed from the 
schedule of assessments. 
Section 8.2.3, 
Electrocardiogram 
ECG added to safety assessments. 
ECGs added to safety 
assessments to measure PR, 
QRS, QT, and QTc intervals. 
Section 8.2.5, Suicidal risk 
monitoring 
-Removed statement that an electronic 
version of the C-SSRS scale will be 
used for screening as well as to assess 
suicidal ideation and behavior that may 
occur during the study. 
-Corrected that the 
“Screening/Baseline” version of the C-
SSRS should only be used at the 
Screening Visit and not anymore at the 
Baseline Visit, and that the “Since Last 
Visit” version should be used at all 
other timepoints, including at the 
Baseline Visit. 
 
 
 
-An electronic version of the 
C-SSRS scale will not be 
used in this study. 
 
 
 
-The Screening/Baseline 
version of the C-SSRS 
should only be used at the 
Screening Visit and not 
anymore at the Baseline 
Visit. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.7, Biomarkers 
Removed requirement for blood 
sampling for exploratory biomarker 
analyses. 
Collection of additional 
specimens is no longer 
necessary because the 
exploratory biomarker 
specimen analyses could be 
performed with the existing 
back-up specimens, which 
are collected as part of the 
pharmacokinetic/ 
pharmacodynamic analyses. 
Section 9.4.1, Safety 
analyses 
Added to clarify that ECG will also be 
presented in listings and summarized 
over time. 
Added to clarify that the clinical 
laboratory, physical examination, and 
ECG assessments conducted at 
screening will be considered as baseline 
values for the assessment of the other 
safety endpoints. 
As clinical laboratory, 
physical examination, and 
ECG assessments are not 
performed at the Baseline 
Visit in this study, text was 
added to clarify and confirm 
that the respective screening 
assessments will be 
considered as baseline when 
assessing the other safety 
endpoints.  
Section 10.4, Appendix 4: 
Contraceptive guidance and 
collection of pregnancy 
information, Table 10-2 
Removed footnote “c” regarding 
hormonal contraception.   
No drug-drug interactions are 
expected; therefore, footnote 
“c” was removed in order to 
streamline the contraceptive 
guidance and to avoid any 
confusion. 
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Amendment 2 (21 Oct 2022) 
Overall Rationale for the Amendment: 
The protocol amendment was considered necessary to remove the SAE reporting requirement 
from the C-SSRS assessment for a positive response to Question 4. The question asks whether 
the participant has had suicidal thoughts or ideations since the last visit. Adverse event or SAE 
reporting following C-SSRS assessment should follow the standard processes as described in 
Section 8.3 and Section 10.3. 
Additional changes include defining the number of missed doses that constitutes a major 
protocol deviation and clarifying that the withholding of cholinesterase inhibitors for 10 hours is 
required only prior to the QMG assessment and not prior to the MG-ADL administration. The 
table below does not include correction of minor typographical errors and formatting/stylistic 
changes. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 6.4, Treatment 
Compliance 
Added statement that if a participant 
misses 10 or more consecutive doses, 
he/she must notify the investigator 
immediately, the medical monitor 
should be consulted, and this will be 
considered a major protocol deviation. 
To define the threshold of 
missed doses that will require 
review by the medical 
monitor and recording of a 
major protocol deviation.  
Section 6.5.1, Permitted 
concomitant treatments 
(medications and therapies) 
Clarified that withholding of 
cholinesterase inhibitors 10 hours prior 
applies to QMG (not required for 
MG-ADL assessment). 
Withholding of 
cholinesterase inhibitors is a 
requirement for QMG, not 
for MG-ADL.  
Section 8.1.1.1, MG-ADL 
Removed requirement for withholding 
cholinesterase inhibitors 10 hours prior 
to MG-ADL assessment. 
Considering the 7 days recall 
period for answering the 
questions, withholding of 
cholinesterase inhibitors is 
not a requirement for MG-
ADL. 
Section 8.2.5, Suicidal risk 
monitoring 
Added statement that families and 
caregivers should be instructed to 
monitor participants for/ report 
emergence of unusual changes in 
behavior or emergence of suicidal 
ideation and behavior. 
Removed statement that a positive 
response to question 4 on the “since last 
visit” C-SSRS must be reported to UCB 
via the SAE process. 
Removal of ambiguous 
wording specific to C-SSRS 
Question 4 and clarification 
of the role of caregivers in 
family in reporting changes 
in behavior. Adverse events 
or SAEs reporting following 
C-SSRS assessment should 
follow the standard processes 
as described in Section 8.3 
and Section10.3.  
 
 
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11 
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Muscle nerve. 2012;45(6):820-5. 
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Vu T, Meisel A, Mantegazza R, et al. Terminal Complement Inhibitor Ravulizumab in 
Generalized Myasthenia Gravis. NEJM Evidence. 2022; 1(5). 
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activities of daily living profile. Neurology. 1999;52(7):1487-9. 
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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:
mg0017-protocol-amend-3-30Nov2022
Version:
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Document Number:
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Title:
mg0017 protocol amendment 3 30 Nov 2022
Approved Date:
30 Nov 2022
Document Approvals
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Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 30-Nov-2022 14:29:26 GMT+0000
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Name: 
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Date of Signature: 30-Nov-2022 14:36:41 GMT+0000
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Date of Signature: 30-Nov-2022 15:59:11 GMT+0000
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SAP_001.pdf: 
UCB 
 
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Statistical Analysis Plan Amendment 4 
Zilucoplan 
MG0017 
 
 
 
Confidential 
Page 1 of 66 
 
STATISTICAL ANALYSIS PLAN  
AMENDMENT 4 
Study: MG0017  
Product: Zilucoplan 
 
A PHASE 3B, MULTICENTER, OPEN-LABEL, SINGLE-ARM 
STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND 
EFFICACY OF ZILUCOPLAN IN PARTICIPANTS WITH 
GENERALIZED MYASTHENIA GRAVIS SWITCHING FROM 
INTRAVENOUS COMPLEMENT COMPONENT 5 INHIBITORS 
TO SUBCUTANEOUS ZILUCOPLAN 
 
Sponsor Name: UCB Biopharma SRL 
Legal Registered Address: Allée de la Recherche 60 
 1070 Brussels | BELGIUM 
 
Regulatory Agency Identifier Number(s): 
IND Number: 
134340  
Confidentiality Statement 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
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Statistical Analysis Plan Amendment 4 
Zilucoplan 
MG0017 
 
 
 
Confidential 
Page 2 of 66 
TABLE OF CONTENTS 
VERSION HISTORY ................................................................................................................ 4 
Amendment 1.0 ...................................................................................................................... 4 
Amendment 2.0 ...................................................................................................................... 6 
Amendment 3.0 .................................................................................................................... 12 
Amendment 4.0 .................................................................................................................... 18 
LIST OF ABBREVIATIONS .................................................................................................. 19 
1 
INTRODUCTION ........................................................................................................... 22 
1.1 
Objectives and Estimands/Endpoints ........................................................................... 22 
1.2 
Study design ................................................................................................................. 25 
2 
STATISTICAL HYPOTHESES ...................................................................................... 26 
3 
SAMPLE SIZE DETERMINATION .............................................................................. 26 
4 
POPULATIONS FOR ANALYSIS ................................................................................. 27 
5 
STATISTICAL ANALYSES .......................................................................................... 27 
5.1 
General Considerations ................................................................................................ 27 
5.1.1 
General study level definitions ............................................................................ 29 
5.1.1.1 
Analysis Time Points ................................................................................. 29 
5.1.1.2 
Protocol Deviations ................................................................................... 31 
5.1.1.3 
Treatment assignment and treatment groups ............................................. 31 
5.1.1.4 
Center pooling strategy ............................................................................. 31 
5.1.1.5 
Coding dictionaries .................................................................................... 31 
5.1.1.6 
Multicenter studies .................................................................................... 31 
5.1.1.7 
Missing data .............................................................................................. 32 
5.1.1.8 
Handling of repeated and unscheduled measurements .............................. 32 
5.1.1.9 
Handling of rescue therapy visits .............................................................. 32 
5.1.1.10 
Handling of missing dates and times ......................................................... 32 
5.2 
Participant Dispositions ............................................................................................... 34 
5.3 
Planned efficacy/outcome analyses ............................................................................. 34 
5.3.1 
Secondary efficacy estimand/secondary endpoint analyses ................................ 34 
5.3.1.1 
Main secondary efficacy endpoint............................................................. 34 
5.3.1.2 
Additional secondary efficacy endpoint .................................................... 36 
5.3.2 
Other efficacy endpoint analyses ......................................................................... 36 
5.4 
Planned safety and other analyses................................................................................ 37 
5.4.1 
Extent of Exposure .............................................................................................. 37 
5.4.2 
Adverse Events .................................................................................................... 38 
5.4.2.1 
Data considerations ................................................................................... 38 
5.4.2.2 
AE summaries ........................................................................................... 39 
5.4.3 
Other Safety Assessments .................................................................................... 41 
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5.4.3.1 
AEs of Special Interest and AEs of Interest .............................................. 41 
5.4.3.2 
Clinical laboratory evaluations .................................................................. 42 
5.4.3.3 
Vital Signs ................................................................................................. 45 
5.4.3.4 
Electrocardiograms .................................................................................... 45 
5.4.3.5 
Physical examination ................................................................................. 46 
5.4.3.6 
Columbia-Suicide Severity Rating Scale (C-SSRS) ................................. 46 
5.5 
Other Analyses ............................................................................................................. 47 
5.5.1 
Other endpoints and/or parameters ...................................................................... 47 
5.5.1.1 
Pharmacokinetics ....................................................................................... 47 
5.5.1.2 
Pharmacodynamics .................................................................................... 48 
5.5.1.3 
Time needed for administration of SC ZLP .............................................. 48 
5.5.1.4 
Participants’ treatment satisfaction............................................................ 48 
5.5.1.5 
Participants’ treatment preference ............................................................. 48 
5.5.1.6 
Genomics ................................................................................................... 48 
5.6 
Subgroup analyses ....................................................................................................... 48 
5.7 
Interim Analyses .......................................................................................................... 48 
5.8 
Data Monitoring Committee (DMC) or Other Review Board ..................................... 49 
6 
SUPPORTING DOCUMENTATION ............................................................................. 49 
6.1 
Appendix 1 Non-key analysis specifications ............................................................... 49 
6.1.1 
Baseline characteristics and demographics ......................................................... 49 
6.1.2 
Protocol deviations .............................................................................................. 50 
6.1.3 
Medical history .................................................................................................... 50 
6.1.3.1 
Medical history (other than MG disease history) ...................................... 50 
6.1.3.2 
gMG disease history .................................................................................. 50 
6.1.4 
Prior/concomitant/follow-up medications ........................................................... 51 
6.1.4.1 
Prior/concomitant medications classification ............................................ 51 
6.1.4.2 
Prior and concomitant medications (non-MG therapy) ............................. 52 
6.1.4.3 
MG Specific Prior and Concomitant Medications .................................... 52 
6.1.5 
Data derivation rules ............................................................................................ 54 
6.1.5.1 
MG Activities of Daily Living score (MG-ADL score) ............................ 54 
6.1.5.2 
Quantitative Myasthenia Gravis (QMG) Score ......................................... 54 
6.1.5.3 
Myasthenia Gravis Quality of Life (MG-QoL 15r) ................................... 56 
6.1.5.4 
Minimal Symptom Expression (MSE) ...................................................... 57 
6.1.5.5 
MGFA Post-Intervention Status (MGFA-PIS) .......................................... 57 
6.1.5.6 
TSQM-9 questionnaire .............................................................................. 57 
6.1.6 
AEs of Interest ..................................................................................................... 58 
6.1.7 
Potentially Clinically Significant Criteria for Safety Endpoints ......................... 61 
6.1.8 
Extent of Exposure .............................................................................................. 61 
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Statistical Analysis Plan Amendment 4 
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6.1.9 
COVID-19 terms ................................................................................................. 62 
6.2 
Appendix 2: Abnormality criteria for Laboratory, Vital Sign and Electrocardiogram 
Parameters .................................................................................................................... 63 
6.2.1 
Laboratory Assessments Marked Abnormality Criteria ...................................... 63 
6.2.2 
Marked Abnormalities Vital Signs ...................................................................... 64 
6.2.3 
Marked Abnormalities Electrocardiogram (ECG) ............................................... 65 
6.3 
Appendix 3: Changes to Protocol-Planned Analyses .................................................. 65 
7 
REFERENCES ................................................................................................................ 66 
 
VERSION HISTORY 
SAP Version 
Approval Date 
Change 
Rationale 
1.0 
25th October 2022 
Not Applicable 
Original version 
Amendment 1.0 
19th January 2023 
Described below 
 
Amendment 2.0 
17th August 2023 
Described below 
 
Amendment 3.0 
11 March 2024 
Described below 
 
Amendment 4.0 
01 November 2024 
Described below 
 
 
Amendment 1.0 
The purpose of the SAP amendment 1.0 is to reflect the introduction of an optional Extension 
Treatment Period in the study design, as described in the protocol amendment 3 (dated 30 Nov 
2022). The optional Extension Treatment Period allows access to zilucoplan for participants who 
wish to continue receiving it after completing the 12-week Main Treatment Period of the study. 
It allows for study participants to continue receiving zilucoplan treatment until the approval of 
the marketing application for the indication of generalized myasthenia gravis (gMG) in the US or 
until further notice from the Sponsor.  
The table below does not include correction of minor typographical errors and 
formatting/stylistic changes. 
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Statistical Analysis Plan Amendment 4 
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MG0017 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Introduction 
Change protocol amendment 2.0 dated 
24 October 2022 to protocol amendment 
3.0 dated 30 November 2022. 
Updates 
Section 1.1 Objectives and 
Estimands/Endpoints 
Table 1.1: Objectives and 
estimands/endpoints 
Section 1.2 Study Design 
Section 5.1.1.1.2 End date of the 
Treatment Periods 
Section 5.1.1.1.3.1 Study 
periods for safety and efficacy 
data 
Section 5.1.1.1.4 Mapping of 
assessments performed at Early 
Discontinuation Visit 
Section 5.1.1.1.5 Definition of 
Baseline values 
Section 5.2 Participant 
Dispositions 
Section 5.3.2 Other efficacy 
endpoint analyses 
Section 5.4.1 Extent of 
Exposure 
Section 5.7 Interim Analysis 
Section 6.1.2 Protocol 
deviations 
Section 6.1.4.1 
Prior/concomitant medications 
classification 
Section 6.1.8 Extent of 
Exposure 
Overall design of the study, treatment 
groups and duration updated to include 
the Extension Treatment Period. 
Endpoints updated to define the 
duration.  
End date of treatment periods defined to 
align with the different periods. 
Definitions of study periods. 
To include an optional 
Extension Treatment 
Period in the study and 
allow eligible 
participants who have 
completed the 12-week 
Main Treatment Period 
to have continued access 
to zilucoplan. 
 
 
 
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Statistical Analysis Plan Amendment 4 
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MG0017 
 
 
 
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Amendment 2.0 
The purpose of the SAP amendment 2.0 is to make the changes as listed in the next table.  
The table below does not include correction of minor typographical errors and 
formatting/stylistic changes. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 4 
Populations for 
Analysis 
Deleted text: 
• 
Screened Set (ScS): The ScS will 
include all screened participants 
including screen failures (see 
Section 6.3) 
• 
Safety Set (SS): The SS will include all 
study participants who received at least 
1 dose of study medication and will be 
used for the demography and safety 
analyses. 
 
• Screened Set was redundant. 
 
 
• Section 6.1.1: “In case there is 
a difference of more than 5 
study participants, those 
descriptive statistics will be 
duplicated in the SS.” 
Section 5.1.1.1.3.1 
Study periods for 
safety and efficacy 
data 
 
Added underlined text for the Safety 
Follow Up (SFU) Period during the Main 
Treatment Period: 
• 
SFU Period: 40 days (after the last dose 
for patients who do not enter the 
extension period or do not transition to 
commercially available ZLP directly 
after the Week 12 visit). 
To define the rules for the 
participants to enter the period 
uniformly across the section. 
Section 5.1.1.1.4 
Mapping of 
assessments 
performed at (Early) 
Withdrawal Visit 
 
Section title was updated from: 
• 
Mapping of assessments performed at 
Early Discontinuation Visit, 
to 
• 
Mapping of assessments performed at 
(Early) Withdrawal Visit 
Early discontinuation visit is not 
defined based on the study 
protocol 
Section 5.1.1.7.3 
Missing data due to 
COVID-19 
 
• 
Added clarification that the protocol 
deviations related to COVID-19 will be 
documented only in listings. 
 
 
 
• COVID-19 related protocol 
deviations are mostly related 
to missed visits due to 
COVID-19 social restrictions 
or COVID-19 infections; 
currently the pandemic period 
is over and only limited such 
PD occurrences are expected; 
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Statistical Analysis Plan Amendment 4 
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MG0017 
 
 
 
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• 
Below text is deleted: 
If the WHO declares an end to the 
pandemic prior to the end of the study, 
included additional summary analyses 
based on the COVID-19 pandemic period 
(during/post). 
data can be documented only 
in listings. 
 
• By the time WHO declared 
the end of the pandemic 
period (05 May 2023) 5 out of 
the 20 patients had entered the 
study. During the end of the 
pandemic period COVID-19 
social restrictions had been 
removed; summaries could not 
be affected by COVID-19 
outbreak at the time being. 
Section 5.2 
Participant 
Dispositions 
Deleted text: 
• 
Reasons for screen failures will be 
summarized using the ScS for overall 
ES 
• 
Disposition of analysis sets will be 
summarized by treatment groups and 
overall by analysis sets (ES, ITT, 
mITT, SS, PK-PPS, PD-PPS). 
Percentages will be based on the 
number of participants in the ES 
overall.  
• 
Finally, if the WHO declares an end to 
the pandemic prior to the enrollment of 
the last study participant, the number of 
study participants enrolled during each 
COVID-19 pandemic (during/post) 
period as well as the number of study 
participants still in the study during 
each COVID-19 pandemic period will 
be summarized in one table on the ES. 
The table will be done overall. 
 
• Screen Set is deleted from the 
SAP 
 
• MG0017 is a single arm trial 
 
 
 
• By the time WHO declared 
the end of the pandemic 
period (05 May 2023) 5 out of 
the 20 patients had entered the 
study. Towards the end of the 
pandemic period COVID-19 
social restrictions had been 
removed; enrollment could not 
be affected by COVID-19 
outbreak. 
Section 5.3.1.1.2 
Main analytical 
approach 
Deleted text: 
CFB in MG-ADL score will be summarized 
by visit using descriptive statistics in the 
mITT. CFB MG-ADL will be listed for all 
participants of the mITT with visit flagged 
if the visit was done prior to the COVID-19 
pandemic cut-off date. 
Any flag related to the COVID-
19 pandemic cut-off date will 
not be issued. No output related 
to the COVID-19 pandemic 
period (during/post) will be 
created. 
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Statistical Analysis Plan Amendment 4 
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MG0017 
 
 
 
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Section 5.3.2 Other 
efficacy endpoint 
analyses 
• 
Deleted text: 
For the MG-ADL and QMG responder rate 
the number and percentage of participants 
who have a reduction (i.e., improvement) of 
≥ X will be summarized by treatment group 
in the mITT at Week 12. 
 
• 
Added text as clarification regarding 
the definition of MG-ADL and QMG 
response: 
The MG-ADL score responder rate will 
be assessed based only on participants 
having an MG-ADL score ≥ 3 at 
Baseline, while the QMG score 
responder rate will be assessed based 
only on participants having an QMG 
score ≥ 5 at Baseline 
• MG0017 is a single arm trial 
 
 
 
 
 
 
• Response cannot be 
determined for participants 
with MG-ADL score < 3 with 
QMG score < 5 at Baseline 
Added text:  
Individual line plots with individual values 
of Total MG-ADL, QMG and MG-QoL15r 
scores will be created in mITT. 
For participants infected with COVID-19 as 
per the AE page, CFB in QMG and MG-
QOL15r score will be listed by visit 
separately. 
 
To illustrate individual time 
course of MG-ADL and QMG 
scores 
Section 5.7 Interim 
Analysis 
Added text: If further interim analysis will 
be considered during the Main Treatment 
Period, then this will be of exploratory 
nature and only descriptive statistics will be 
provided. 
To clarify the descriptive 
nature of the interim cuts. 
5.4.2 Data 
consideration 
Added text: 
The CTCAE displays Grades 1 through 5 
with unique clinical descriptions of severity 
for each AE based on this general 
guideline:   
- Grade 1 Mild; asymptomatic or mild 
symptoms; clinical or diagnostic 
observations only; intervention not 
indicated.   
- Grade 2 Moderate; minimal, local or 
noninvasive intervention indicated; 
 
Data collected in the eCRF is 
not based on the CTCAE 
categories. Definitions needed to 
be added to map the AE 
intensity (mild, moderate, 
severe) to CTCAE grading. 
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Statistical Analysis Plan Amendment 4 
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MG0017 
 
 
 
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limiting age-appropriate instrumental 
activities of daily living.   
Note: instrumental activity of daily 
living refers to preparing meals, 
shopping for groceries or clothes, using 
the telephone, managing money, etc. 
- Grade 3 Severe or medically significant 
but not immediately life-threatening; 
hospitalization or prolongation of 
hospitalization indicated; disabling; 
limiting self care activities of daily 
living. 
Note: self care activities of daily living 
refer to bathing, dressing and 
undressing, feeding self, using the toilet, 
taking medications, and not bedridden 
- Grade 4 Life-threatening consequences; 
urgent intervention indicated.   
- Grade 5 Death related to AE. 
Programming mapping definitions are 
added. 
5.4.2.2 AE 
summaries 
Added text: All AEs within a 7-day period 
post each COVID-19 vaccination will be 
summarized for all vaccinated participants. 
Two separate listings will display the AEs 
after adjustment of the interval censoring 
and the concomitant COVID-19 
vaccination. 
As per UCB guidance related to 
COVID-19 vaccination 
Section 5.4.3.1 
Title changed from “AEs of special 
interest” to “AEs of Special Interest and 
AEs of Interest”. 
Definition of AEs of Interest is provided 
Adverse Events (AEs) of 
hypertensitivity, anaphylactic 
reactions, drug related hepatic 
disorders and malignancies or 
unspecified tumors were added 
to the AE summaries in order to 
further assess the ZLP safety 
and be aligned within the ZLP 
program. 
5.4.3.2.4 Assessment 
of potential liver 
toxicity 
Added criterion: AST or ALT >3xULN 
with INR>1.5 (if INR is measured) 
To define Hy’s law according to 
the study protocol 
5.5.1 
Pharmacokinetics 
Deleted text: 
A spaghetti plot of combined individual 
concentration versus time profiles will be 
presented by analyte in linear and semi-
No figures to be created as 
based on the study protocol PK 
will be measured in only two 
timepoints. 
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logarithmic scale with all participants 
overlaid on the same plot.  
Additionally, mean (+SD) plasma 
concentration versus time overlaid for both 
analytes will also be presented for all 
scheduled timepoints on a linear and semi-
logarithmic scale. The SD will not be 
provided on the semi-logarithmic scale.  
All figures will include the LLOQ on the 
semi-logarithmic plots. 
5.5.1.4 Participants’ 
treatment satisfaction Added text: 
• Bar charts illustrating the mean and 
standard error at each visit by domain will 
be provided.   
• Individual participant listings will be 
provided for all participants and for 
participants infected with COVID-19 as 
per the AE page. 
 
• To facilitate the data results 
interpretation 
 
• To align with the efficacy 
questionnaire data 
5.7 Interim Analyses 
Added text: 
“If further interim analysis will be 
considered during the Main Treatment 
Period, then this will be of exploratory 
nature and only descriptive statistics will be 
provided.” 
 
Clarification on the analysis 
purposed of any interim cut 
during the main treatment period 
6.1.1 Baseline 
characteristics and 
demographics 
• Deleted text: 
Additional subgroup summary will be 
presented based on the enrolled date 
relative to the cut-off date by during/post 
COVID-19 pandemic period based on the 
mITT. 
 
• An additional cut off of BMI=35 m/kg2 is 
added 
 
• Any summaries based on the 
COVID-19 periods will not be 
considered. 
 
 
 
• As per UCB updated guidance  
Section 6.1.2 
Protocol deviations 
• IPD summaries to be provided in the 
mITT 
Deleted text:  
A summary of number and percentage of 
participants having important protocol 
deviation by relationship to COVID-19 will 
 
 
• Randomized Set (RS) is not 
applicable to MG0017. 
 
 
 
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be provided for the RS population by 
treatment group 
 
• Added text: 
“A COVID-19 related flag will be present 
in IPD listings.” 
 
 
 
 
• Clarification 
 
Section 6.1.2.3 gMG 
disease history 
Text on summary statistics of the following 
parameters is deleted: 
• 
Family members have MG (Yes, No) 
• 
Diagnosed with Thymoma (Yes, No) 
• 
Prior Thymectomy (No: Yes [Total 
Thymectomy, Subtotal Thymectomy]) 
• 
Time since Thymectomy (months), 
calculated as (Date of Study Day 1 – 
Date of Thymectomy)/ (365.25/12) 
Note: If the Date of Thymectomy day and 
month are missing impute July 2nd, if only 
the day is missing impute the 15th. If the 
imputed Date of Thymectomy date is later 
than the date of Study Day 1, impute the 
date of Study Day 1. 
Information is not recorded in 
the eCRF 
Text added: 
“Note: Generalized symptoms at onset: 
participants with respiratory symptoms or 
symptoms in the limb, bulbar or any other 
location; participants at this category might 
also have ocular symptoms at onset as 
well.” 
 
Information was missing 
Text on summary statistics is added: 
• Reason for switching to study medication 
(Logistical challenges including travel 
and time spent at a hospital, Challenges 
with venous access, Lengthy intravenous 
infusion, Other) 
Information was missing from 
the section 
Section 6.1.4.3 MG 
Specific Prior and 
Concomitant 
Medications 
Text is added in Table 6.2 Medication 
Class: 
To update the table  
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Group F: Pyridostigmine Bromide is added 
at the Group F therapies 
Footnote: *plasma exchange will be on the 
Procedures eCRF (if concomitant 
procedure). 
6.1.6 AEs of Interest 
Algorithmic approach to derivation of AEs 
of Interest in added 
To summarize the AEIs 
Section 6.2.1 
Laboratory 
Assessments Marked 
Abnormality Criteria 
• Text labs from Table 6-6 Laboratory 
Abnormalities: 
• Calcium, Albumin, CRP and GGT labs 
are deleted 
• According to the study 
protocol, albumin, CRP and 
GGT are not collected. 
• Calcium as parameter of 
abnormalities is checked via 
the Corrected Calcium which 
cannot be derived in the study. 
6.3 Appendix 3: 
Changes to Protocol-
Planned Analyses 
Deleted text: 
The Screened Set population has been 
added to ease the display of some 
descriptive statistics. 
Screen Set has been deleted 
from the SAP Amendment 2 
 
Amendment 3.0 
The purpose of the SAP amendment 3.0 is to make the changes as listed in the table below.  
The table below does not include correction of minor typographical errors and 
formatting/stylistic changes. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 5.1.1.10 
Handling of missing 
dates and times 
The following crossed-out text is deleted: 
Discharge date refers to the date of the 
end of study visit for completed or the 
date of discontinuation for participants 
that were withdrawn. 
To remove the redundant 
text, as the date of 
discontinuation for 
withdrawn participants is 
captured in the eCRF in the 
safety follow up visit. 
Section 5.4.1 Extent 
of Exposure 
• The following text is added:  
"The missed doses will be derived based 
on the expected number of daily doses 
the participant should receive within a 
defined period minus the total number of 
doses he/she has received during that 
period. For this derivation, the number of 
total syringes administered to a 
participant at each visit will be 
considered via the total number of kits 
administered at each visit, assuming that 
• The number of missed 
doses are not collected in 
the eCRF and should be 
derived. Added text is to 
document that the 
number of missed daily 
doses will be derived 
based on the number of 
administered kits vs 
number of returned 
syringes. This derivation 
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each kit contains 7 syringes to be used 
for 7 daily doses.” 
 
• The following text is added:  
For the Main Treatment Period, time to 
IMP discontinuation is defined as: Date 
of last IMP dose – date of first IMP dose 
+ 1. Participants that did not early 
withdraw should be censored at the date 
of Main Treatment Period completion. 
For the Overall Treatment Period, time to 
IMP discontinuation is defined as: Date 
of last IMP dose – date of first IMP in 
Main Treatment Period + 1. Participants 
that did not (early) withdraw should be 
censored at the date of their last contact.  
For the Extension Treatment Period, time 
to IMP discontinuation is defined as: 
Date of last IMP dose – date of first IMP 
in Extension Treatment Period+ 1. 
Participants that did not withdraw should 
be censored at the date of their last 
contact.  
For all treatment periods, participants 
that switch to commercially available 
Zilucoplan are not considered as 
discontinuation events; for the time to 
event analysis exposure will be censored 
at the date of their last contact. 
rule is to be incorporated 
in the summary tables. 
 
• To document the 
derivation of the time to 
IMP discontinuation in 
the Main, Extension and 
Overall Treatment period 
in order to create the 
Kaplan-Meier curves. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 5.3.1.1 Main 
analytical approach 
• The underlined text is added: 
For the efficacy endpoint, the CFB to 
Week 12 in MG-ADL score will be 
modeled using a mixed model for 
repeated measures (MMRM) with 
baseline MG-ADL Score and Week 1, 2, 
4, 8 and 12 as fixed factors and baseline 
MG-ADL Score by visit as interaction 
term. The Least square mean (LSM) 
followed by the 95% Confidence Interval 
(CI) and standard error of the 
corresponding CFB at each visit will be 
reported. 
 
 
• To provide further clarity 
on the MMRM model 
constrains and on the 
analysis outputs. 
 
 
 
 
 
 
 
 
 
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• The following text is added: 
The NI of Week 12 MG-ADL over the 
Baseline MG-ADL, will be shown if the 
upper limit of the one sided 97.5% CI (or 
the two sided 95% CI) of the LSM MG-
ADL CFB at Week 12 does not cross the 
non inferiority margin of 2 points.  
• To update the SAP text 
with the non-inferiority 
statistical rule as 
proposed by the 
authorities. 
Section 5.4.2.2 AE 
summaries 
• The following text is added for the 
AE summaries to be produced: 
-Any TEAEs above 5% of occurrence 
 
• The following underlined text is 
added: 
The number, percentage of participants 
with TEAEs will be summarized by 
maximum intensity (mild, moderate and 
severe), SOC, and PT as well as by 
intensity (mild, moderate and severe), 
SOC, and PT. 
 
• The following text is deleted:  
A listing of all TEAEs during the 
COVID-19 infection will be provided for 
participants infected by COVID-19. A 
TEAE during the COVID-19 infection is 
a TEAE that started from 5 days prior to 
the start date/ onset of a COVID-19 
infection until the end date of the 
infection. If the COVID-19 infection is 
ongoing or the end date is missing at the 
time of database lock, TEAEs will be 
included up to 3 months (91 days) after 
the start of the infection or until the end 
of study date, which occurs first.  
 
• The following text is deleted:  
“Two separate listings will display the 
AEs after adjustment of the interval 
censoring and the concomitant COVID-
19 vaccination.” 
• Table is part of the 
disclosure outputs. 
 
 
 
• TEAEs summary by 
intensity is added so that 
the total number of 
events per Adverse Event 
will be counted and 
presented.  
 
 
• The impact of COVID-
19 pandemic on safety, 
will be assessed by other 
outputs included but not 
limited to outputs 
reporting all COVID-19 
related TEAEs.  
 
 
 
 
 
 
 
• To remove the duplicate 
sentence. 
Section 5.4.3.1 AEs 
of Special Interest 
and AEs of Interest 
• Injection site reactions are added as 
part of the AEs of Interest 
 
• Injection site reactions 
are missed from the 
previous SAP version. 
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• The following crossed out text is 
deleted:  
The number and percentage of 
participants who experience each AE of 
Interest will be summarized treatment 
group separately for each AE of interest.  
• This is one arm study. 
5.4.3.2.3 Laboratory 
Marked 
abnormalities 
 
The underlined text is added: 
“Treatment-emergent is defined as meeting 
the criteria at any post-Baseline visit while 
criteria are not present before dosing.” 
To correct the TEMA 
definition  
5.4.3.2.4 
Assessment of 
potential liver 
toxicity 
Liver Function Tests criteria changed from “ 
LFT > * x ULN” to “LFT ≥ * x ULN” 
Update is according to the 
UCB internal guidance for LFT 
standard shells issued on 18 
January 2024. 
5.4.3.4 
Electrocardiograms 
Units are added at the ECG assessments 
To provide further clarity 
5.4.3.6 Columbia-
Suicide Severity 
Rating Scale (C-
SSRS) 
 
• The following text is added: 
C-SSRS instrument recorded at screening 
visit references the lifetime period and 
the past six months period. Baseline to 
end of study visit summaries reference 
the period prior to the visit assessed. 
 
• The following underlined text is 
added: 
“Results of the C-SSRS, as well as the 
treatment emergent item at Week 12 (or 
(early) withdrawal will be summarized in 
SS by scheduled timepoint using the 
number of participants and percentage 
with:” 
 
 
• C-SSRS has two versions: 
a. Screening/Baseline version 
b. Since last visit version  
Text has been added for further 
clarity. 
 
 
 
• C-SSRS is also recorded at 
the (early) withdrawal visit.  
Also the “complete suicide 
item” is not subject to the “C-
SSRS Screening/Baseline 
version” 
 
 
6.1 Baseline 
characteristics and 
demographics 
 
Weight (kg) categories are changed from 
“<56, 56-<77, 77 - <150, ≥ 150” to  
“<43, 43 - <56, 56-<77, 77 - <150, ≥ 
150” 
To reflect the protocol defined 
categories. 
 
6.1.4.3 MG 
Specific Prior and 
Concomitant 
Medications 
• “IVIG, SCID and Immunoglobulins 
NOS” terms are removed from Group 
D. 
• Following treatments are added: 
Plasmapheresis is added in Group D:  
• IVIG or SCIG were included 
in both Group B and Group 
C 
• For completeness in MG 
treatment therapies. 
 
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Galantamine is added in Group F  
Rozanolixizumab is added in Group 
H 
6.1.6 AEs on 
Interest 
Injection site reactions derivation is 
added at Table 6-5: AEs of Interest 
selection criteria:  
TEAE with HLT=’Injection site 
reactions’ or HLT=’Administration site 
reactions NEC’ 
Injection site reactions 
derivation is missing from 
the previous SAP version. 
 
6.1.8 Extent of 
Exposure 
 
• The denomination for the calculation 
of the reference period with respect to 
treatment compliance is changed as 
follows: 
Compliance between 2 study visits:  
Day of the visit in clinic – Day of the 
previous visit in clinic +1) changed 
to: Date the syringes are returned in 
clinic – Date the syringes are 
dispensed in clinic. 
 
Overall Compliance in the Main 
Treatment Period:  
Day of the last visit in clinic in the 
Main Treatment Period – Day of the 
baseline visit + 1 changed to: Date the 
last syringes are returned in clinic in 
the Main Treatment Period – Date the 
first syringes are dispensed in clinic 
 
Compliance in the Overall Treatment 
Period:  
Day of the last visit in clinic in the 
Extension Treatment Period – Day of 
the baseline visit + 1 changed to: Date 
the last syringes are returned in clinic 
in the Extension Treatment Period – 
Date the first syringes are dispensed 
in clinic in the Main Treatment Period 
 
• The following text is added: 
Of note, the number of syringes 
dispensed at each visit will be derived 
based on the number of kits dispensed at 
• To adjust the compliance 
definition so that 
injections administered 
in a clinic visit will be 
part of the compliance 
measures with respect of 
the next time interval. 
Example: injections 
performed on Week 2 
will be considered for the 
compliance between 
week 2 and week 12. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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that visit, assuming that each kit contains 
7 single dose syringes to be used for the 
daily dosing. 
• To further clarify the 
derivation of treatment 
compliance. 
6.2.3 Marked 
Abnormalities 
Electrocardiogram 
(ECG) 
 
• The top label row of Table 6-10: has 
been updated to Treatment Emergent 
Markedly Abnormal Criteria. 
 
• The underlined text is added the 
footnote of Table 6-10: Marked 
Abnormalities (ECG)  
Note: Treatment-emergent Markedly 
Abnormal is defined as meeting the 
criteria at any post-Baseline visit after 
the first dose of IMP and not meeting 
the criteria at Baseline. 
• To capture the table 
contents. 
 
 
• To update and correct the 
Treatment Emergent 
Markedly Abnormal 
(TEMA) definition. 
Section 6.1.6 AEs 
of Interest 
• The following terms are 
added/deleted in Table 6-6: 
Anaphylactic Reactions Categories 
 
Added: 
Group A: Procedural Shock 
Group B: Cough Variant Asthma, 
Enhanced Respiratory Disease, 
Oropharyngeal Oedema, Pharyngeal 
Spam, Pharyngeal Swelling  
Group C: Circumoral Swelling, 
Oedema Blister, Periorbital Swelling, 
Swelling, Swelling of Eyelid 
Group D: Hypotensive Crisis, Post 
Procedural Hypotension 
 
Deleted: 
Group B: Respiratory dyskinesia 
Group C: Generalized erythema, 
Pruritus Generalized, Rash 
Generalized 
• To capture the updates in 
MedDRA v26.1 coding 
dictionary 
 
 
 
 
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Amendment 4.0 
The purpose of the SAP amendment 4.0 is to update the calculation of compliance. 
Section # and Name 
Description of Change 
Brief Rationale 
6.1.8 Extent of 
Exposure 
 
Compliance calculation in the Overall 
Study period has been amended as 
follows: 
• For participants entering in the 
Extension Treatment Period, the 
overall compliance in the Overall 
Treatment Period will be calculated 
as: (total number of syringes 
dispensed – total number of unused 
syringes – total number of 
malfunctioned syringes +1)/(Date of 
last drug administration – Date the 
first syringes are dispensed in clinic 
in the Main Treatment Period 
+1)*100. 
 
The following text has been added: 
•  If the participant was (early) 
withdrawn, then the date to be 
considered in the calculation of 
compliance as the end of exposure 
period will be the date of last 
administration of Zilucoplan and not 
the date the participant returned the 
syringes in clinic. Then, the 
compliance will be calculated as 
follows: (number of syringes 
dispensed at the previous clinic visit 
– number of unused syringes 
returned in clinic – total number of 
malfunctioned syringes +1)/(Date of 
last drug administration – Date the 
syringes are dispensed in clinic + 
1)*100. 
 
 
 
 
• The date the syringes are 
returned in clinic might 
differ from the date of last 
dose administration; thus, 
compliance should be 
measured up to the last 
dose and not up to the 
return date in clinic. 
 
 
 
 
 
 
• As above 
 
 
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LIST OF ABBREVIATIONS 
 
List of Abbreviations 
AE 
Adverse Event 
AEs 
Adverse events 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
ALP 
Alkaline phosphatase 
ALQ 
Above the Limit of Quantification 
AST 
Aspartate aminotransferase 
BLQ 
Below the Limit of Quantification 
BMI 
Body Mass Index 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
C5 
Complement component 5 
CFB 
Change from baseline 
CI 
Confidence interval 
COVID-19 
Coronavirus Disease 2019 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of variation 
DAP 
Data Analysis Plan 
DMC 
Data Monitoring Committee 
eCRF 
electronic Case Report form 
ECG 
electrocardiogram 
eGFR 
Estimate glomerular filtrate rate 
ES 
Enrolled Set 
EW 
Early withdrawal 
FDA 
US Food and Drug Administration 
geoCV 
Geometric coefficient of variation 
gMG 
Generalized Myasthenia Gravis 
HLT 
High level term 
ICH 
The International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
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List of Abbreviations 
IMP 
investigational medicinal product 
IST 
immunosuppressant therapy 
IV 
intravenous 
IVIG 
intravenous immunoglobulin G 
ITT 
Intention to treat 
kg 
kilogram 
LLoQ 
Lower Limit of Quantification 
LFT 
Liver function tests 
MA 
Marked Abnormality 
MedDRA 
Medical Dictionary for Regulatory Activities 
MG 
Myasthenia Gravis 
MG-ADL 
Myasthenia Gravis -Activities of Daily Living 
MG-QOL 15r 
Myasthenia Gravis MG Quality of Life 15 Item scale revised 
MGFA 
Myasthenia Gravis Foundation of America 
MGFA-PIS 
Myasthenia Gravis Foundation of America Post Intervention Status 
mL 
Milliliter  
MI 
Multiple imputation 
mITT 
Modified Intention to treat 
mg 
milligram 
MSE 
Minimal symptom expression 
NI 
Non inferiority 
PD 
Pharmacodynamic 
PD-PPS 
Pharmadynamic Per Protocol Set 
PEY 
Patient-years exposure 
PK 
Pharmacokinetic 
PK-PPS 
Pharmacokinetic Per Protocol Set 
PLEX 
Plasma exchange 
PPS 
Per Protocol Set 
PR 
Pharmacologic Remission 
PT 
Preferred term 
QMG 
Quantitative Myasthenia Gravis 
SAEs 
Serious Adverse Events 
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List of Abbreviations 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
SD 
Standard deviation 
SFU 
Safety follow up 
SMQ 
Standardized MedDRA Query 
SoC 
Standard of care 
SOC 
System Organ Class 
sRBC 
sheep red blood cell 
SS 
Safety Set 
TBL 
Total bilirubin 
TEAE 
Treatment-Emergent Adverse Event 
TEMAs 
Treatment-emergent marked abnormalities 
TFL 
Table, Figure and Listing 
TSQM-9 
9 item Treatment Satisfaction Questionnaire for Medication 
ULN 
Upper Limit of Normal 
WHO 
World Health organization 
WHODD 
World Health Organization Drug Dictionary 
ZLP 
zilucoplan 
 
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1 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide all information that is necessary 
to perform the statistical analyses of study MG0017. It also defines the summary tables, figures 
and listings (TFLs) to be included in the Clinical Study Report (CSR) according to the protocol. 
This SAP includes safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) 
analyses. Changes to protocol-planned analysis are documented in Section 6.3. Table, Figure and 
Listing specifications are contained in a separate document. 
This SAP is based upon and assumes familiarity with protocol amendment 3.0 dated 30 
November 2022. 
If a future protocol amendment necessitates a substantial change to the statistical analysis of 
study data, this SAP may be amended accordingly. The content of this SAP is compatible with 
the International Council for Harmonization (ICH)/Food and Drug Administration (FDA) E9 
Guidance documents.  
The statistical analyses and production of the outputs described in the SAP will be conducted 
using SAS software version 9.4 or above. The final analyses and outputs will be approved by 
UCB. 
1.1 
Objectives and Estimands/Endpoints 
The estimand corresponding to the primary objective and primary safety analyses are described 
below. The estimands corresponding to the secondary objectives and secondary analyses are also 
described below. 
Table 1.1: 
Objectives and estimands/endpoints 
Objectives 
Estimands/endpoints 
Primary 
To evaluate the safety and 
tolerability of switching from 
intravenous (IV) Complement 
component 5 (C5) inhibitors to 
subcutaneous (SC) Zilucoplan 
(ZLP) in study participants with 
generalized Myasthenia Gravis 
(gMG) 
The primary safety endpoints are: 
• 
Incidence of Treatment Emergent Adverse Events (TEAEs) 
over the Main Treatment Period 
• 
Incidence of TEAEs leading to withdrawal of study medication 
over the Main Treatment Period 
Secondary 
To evaluate the efficacy of SC 
ZLP after switching from IV C5 
inhibitors in study participants 
with gMG 
The secondary efficacy estimand is: 
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Objectives 
Estimands/endpoints 
• 
Treatment: ZLP administered by daily SC injections 
(0.3mg/kg/day) 
• 
Target population: Adult study participants with gMG currently 
receiving an IV C5 inhibitor approved for the treatment of 
gMG according to the protocol-specified inclusion/exclusion 
criteria 
• 
Endpoint: Change from Baseline (CFB) to Week 12 in 
Myasthenia Gravis -Activities of Daily Living (MG-ADL) 
score 
• 
Intercurrent event handling: The intercurrent events considered 
in this study are: 
− 
ICE1: Administration of rescue therapy or changes in 
Standard of Care (SoC) dose regimens. Data collected at 
and after the point of the intercurrent event will be used as 
collected to gain understanding of clinical practice. 
− 
ICE2: Participant discontinuation from the study. It will be 
assumed that the participant had remained on their 
treatment (regardless of rescue therapy administration) 
throughout the study (i.e., a "hypothetical strategy" 
assuming participants did not discontinue the study and 
remained on treatment). 
• 
Population level summary: The mean of the endpoint 
To evaluate the efficacy of SC 
ZLP after switching from IV C5 
inhibitors on an additional 
efficacy endpoint in study 
participants with gMG 
The secondary efficacy endpoint is: 
• 
CFB to Week 12 in the Quantitative Myasthenia Gravis (QMG) 
score 
This endpoint will be analyzed following the same estimand 
structure as defined for the MG-ADL score. The endpoint assessed 
will change accordingly. 
To evaluate safety and 
tolerability of SC ZLP after 
switching from IV C5 inhibitors 
on additional safety measures in 
study participants with gMG 
The secondary safety endpoints are: 
• 
Incidence of serious TEAEs over the Main Treatment Period 
• 
Incidence of study withdrawal over the Main Treatment Period 
Other 
To further explore the efficacy 
of SC ZLP on additional efficacy 
endpoints after switching from 
IV C5 inhibitors in study 
participants with gMG 
The other efficacy endpoints are: 
• 
Time to first receipt of rescue therapy over the Main Treatment 
Period 
• 
Change in SoC therapy medication dose regimen for gMG 
during the Main Treatment Period 
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Objectives 
Estimands/endpoints 
• 
Achievement of Minimal Manifestation Status per Myasthenia 
Gravis Foundation of America Post Intervention Status 
(MGFA-PIS) at Week 12 without rescue therapy 
• 
Achieving minimal symptom expression (MSE), defined as an 
MG-ADL of 0 or 1 at Week 12 without rescue therapy 
• 
CFB to Week 12 in QMG subscores: ocular, bulbar, 
respiratory, limb 
• 
CFB to Week 12 in Myasthenia Gravis MG Quality of Life 15 
Item scale revised (MG-QOL15r) score 
• 
MG-ADL score responder rate (responder is defined as 
achieving ≥ 3-point improvement from Baseline [decrease] at 
Week 12 and not having taken rescue therapy) 
• 
QMG score responder rate (responder is defined as achieving  
≥5-point improvement from Baseline [decrease] at Week 12 
and not having taken rescue therapy) 
To explore the time needed for 
administration of SC ZLP 
The other endpoint is: 
• 
Time needed for administration of SC ZLP 
To explore study participants’ 
treatment satisfaction following 
the use of SC ZLP 
The other endpoint is: 
• 
CFB to Week 12 in 9 item Treatment Satisfaction 
Questionnaire for Medication (TSQM-9) scores 
To explore study participant 
preference following the use of 
SC ZLP 
The other endpoint is: 
• 
Patient Preference assessment at Week 12 
To further evaluate the safety 
and tolerability of SC ZLP after 
switching from IV C5 inhibitors 
on other safety measures in 
study participants with gMG 
The other safety endpoints are: 
• 
CFB to Week 12 in clinical laboratory tests 
• 
CFB to Week 12 in physical examination 
• 
ECG 
• 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
• 
Incidence of TEAEs 
To evaluate the PK of SC ZLP 
after switching from IV C5 
inhibitors 
The other PK endpoint is: 
• 
Plasma concentrations of ZLP and its major metabolites over 
the Main Treatment Period (
) 
To evaluate the PD of SC ZLP 
after switching from IV C5 
inhibitors 
The other PD endpoint is: 
• 
sheep red blood cell (sRBC) lysis assay for evaluation of 
classical complement pathway activation over the Main 
Treatment Period 
C5=complement component 5; CFB=change from Baseline; C-SSRS=Columbia-Suicide Severity Rating Scale; 
gMG=generalized myasthenia gravis; IV=intravenous; MG-ADL=Myasthenia Gravis-Activities of Daily 
Living; MG-QOL15r=Myasthenia Gravis – Quality of Life revised; MGFA-PIS=Myasthenia Gravis 
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Objectives 
Estimands/endpoints 
Foundation of America Post-Intervention Status; MSE=Minimal Symptom Expression; 
PD=pharmacodynamic(s); PK=pharmacokinetic(s); QMG= Quantitative Myasthenia Gravis; SC=subcutaneous; 
SoC=standard of care; sRBC=sheep red blood cell; TEAE=treatment-emergent adverse event; TSQM-9=9-item 
Treatment Satisfaction Questionnaire for Medication; ZLP=zilucoplan 
1.2 
Study design 
MG0017 is a Phase 3b, multicenter, open-label, single-arm study to evaluate the safety, 
tolerability, and efficacy of ZLP in study participants with gMG switching from their current IV 
C5 inhibitor to SC ZLP. 
To be eligible to participate in this study, participants must be adults (≥18 years of age) with a 
documented diagnosis of gMG (Myasthenia Gravis Foundation of America (MGFA) 
Class II-IVa), currently receiving an IV C5 inhibitor approved for the treatment of gMG for at 
least 3 months (for eculizumab) or 4 months (for ravulizumab) prior to Screening (with the last 
dose being administered at the Screening Visit ±3 days), considered to have a clinically stable 
disease as per the Investigator’s judgment prior to Screening, and willing to switch from their 
current IV C5 inhibitor to SC ZLP. 
The planned enrollment is 20 study participants in the US. 
The study includes a 2-week or 8-week Screening Period (for participants receiving eculizumab 
or ravulizumab, respectively), a 12-week Main Treatment Period, and an optional Extension 
Treatment Period. A Safety Follow Up (SFU) Visit should be performed 40 days (±7 days) after 
the last dose of study medication. 
The Screening Visit should be scheduled to coincide with the regularly scheduled study 
participant’s IV C5 inhibitor administration (±3 days). Up to and including the time of the 
Screening Visit, study participants will continue to receive their IV C5 inhibitor at the 
recommended dose regimen. The last regularly scheduled IV C5 inhibitor administration cannot 
occur beyond Day -14 (±3 days) of the Screening Period for study participants receiving 
eculizumab or beyond Day -56 (±3 days) of the Screening Period for study participants receiving 
ravulizumab to ensure approximately a 2-week or 8-week interval between the last regularly 
scheduled IV C5 inhibitor administration and the first SC ZLP administration during the Main 
Treatment Period, respectively. 
At the end of the Screening Period and in case of no more than a 2-point change in study 
participants’ MG-ADL score compared to the Screening Visit, study participants will enter the 
Main Treatment Period and will switch to SC ZLP (IV C5 inhibitor should not be administered 
after the Screening Visit). On Day 1, study participants will receive ZLP 0.3mg/kilogram (kg) 
administered SC. Following in-clinic education and training, all study participants will self-inject 
daily SC doses of study medication for the subsequent 12-weeks. Single-use pre-filled syringes 
in injection devices will be provided for use during the study. Of note, there will be no washout 
period during the study where study participants are not receiving treatment for MG. 
During the Main Treatment Period, study participants will be contacted via phone call at Week 1, 
Week 4, and Week 8 to assess safety and tolerability. During these phone call visits, the 
MG-ADL assessment will also be performed. Study participants will return to the clinic at 
Week 2 and Week 12 to evaluate safety, tolerability, and efficacy. Additional assessments will 
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include questionnaires, PK, and PD. Safety assessments will include adverse event (AE) 
monitoring, physical examination, clinical laboratory tests, and C-SSRS. 
The time needed for preparation and administration of SC ZLP will also be measured during the 
Main Treatment Period in accordance with the Schedule of Activities. 
Study participants are expected to remain on a stable dose regimen of all medications unless 
medically indicated changes become necessary. All SoC therapy medications for gMG should be 
kept at the same dose regimen throughout the study, including corticosteroids and 
immunosuppressant therapy (IST) drugs. If rescue therapy becomes necessary due to major 
deterioration of a study participant’s clinical status, or risk of MG crisis as per the Investigator’s 
judgment, the study participant may receive intravenous immunoglobulin G (IVIG) or plasma 
exchange (PLEX) treatment as rescue therapy. 
Additionally, if deemed needed as per the Investigator’s judgment, study participant may be 
readministered their previous IV C5 inhibitor after discontinuation of the study medication. 
All study participants who complete the Main Treatment Period will have the option to continue 
ZLP treatment in the Extension Treatment Period after the Week 12 visit. If a study participant 
withdraws from the study during the Main Treatment Period, the participant will complete an 
Early Withdrawal (EW) Visit followed by a SFU Visit 40 days (±7 days) after the last dose of 
study medications. Participants who opt not to continue into the Extension Treatment Period will 
complete a SFU Visit 40 days (±7 days) after the last dose of study medication. 
The Extension Treatment Period consists of in-clinic visits every 12 weeks (±7 days) and will 
continue until all participants are withdrawn, until ZLP is approved and available in the US, or 
until further notice from the Sponsor. During these visits, ZLP accountability and resupply will 
be performed, medications updated, and safety will be assessed. Participants who withdraw or 
discontinue ZLP during the Extension Treatment Period will complete a Withdrawal Visit 
followed by a SFU Visit 40 days (±7 days) after the last dose of study medication. Participants 
who transition to commercially available ZLP will complete a Withdrawal Visit but will not 
require a SFU Visit. If by the time a participant completes the Main Treatment Period ZLP is 
commercially available, the participant may transition to commercially available ZLP directly 
following the Week 12 visit at the end of the Main Treatment Period. 
 
2 
STATISTICAL HYPOTHESES 
The null hypothesis for the secondary efficacy endpoint of the secondary efficacy estimand is 
that the ZLP CFB in Week 12 MG-ADL is greater than the non-inferiority (NI) margin of 2. The 
alternative hypothesis is that the ZLP CFB in Week 12 MG-ADL is lower than the NI of 2. 
This secondary efficacy endpoint will be tested at the 1-sided alpha of 0.025. 
No multiplicity adjustment is planned in this study. 
 
3 
SAMPLE SIZE DETERMINATION 
The secondary efficacy estimand will investigate if the Week 12 MG-ADL score is noninferior 
to the Baseline MG-ADL score with an NI margin of 2. It is assumed that the Week 12 CFB has 
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a standard deviation (SD) of 3 and that the true CFB is 0. Given a sample size of 20 study 
participants, the study has approximately 80% power to detect this, based on a 1-sided alpha of 
0.025. 
 
4 
POPULATIONS FOR ANALYSIS 
• Enrolled Set (ES): The ES will include all study participants who signed the ICF. 
• Intention-to-Treat (ITT) Population: The ITT Population will include all eligible study 
participants. Efficacy analyses will be performed on the ITT in case there is a difference of at 
least 5 participants as compared to the modified Intention-to-Treat (mITT) Population. 
• Modified ITT Population (mITT): The mITT Population will include all eligible study 
participants who received at least 1 post-Baseline dose of study medication and had at least 
1 post-Baseline assessment. The mITT Population will be used for all efficacy analyses. 
• Safety Set (SS): The SS will include all study participants who received at least 1 dose of 
study medication and will be used for the safety analyses. 
• Pharmacokinetic Per-Protocol Set (PK-PPS): The PK-PPS will include all study participants 
in the safety population who received at least 1 dose of study medication and had at least 
1 quantifiable PK measurement post dose of study medication without important protocol 
deviations that would affect the PK. The PK-PPS will be used for all PK analyses. 
• Pharmacodynamic Per-Protocol Set (PD-PPS): The PD-PPS will include all study 
participants in the safety population who received at least 1 dose of study medication and had 
at least 1 quantifiable PD measurement post dose of study medication without important 
protocol deviations that would affect the PD. The PD-PPS will be used for all PD analyses. 
 
5 
STATISTICAL ANALYSES 
5.1 
General Considerations 
Statistical analysis and generation of tables, figures, participant data listings, and statistical 
output will be performed using SAS® Version 9.4 or higher. All tables and listings will use 
Courier New font size 9. 
All clinical study data will be presented in participant data listings. 
Descriptive statistics will be displayed to provide an overview of the study results. For 
continuous variables, descriptive statistics will include number of participants with available 
measurements (n), mean, SD, median, minimum, and maximum. For categorical variables, the 
number and percentage of participants in each category will be presented. Unless otherwise 
noted, the denominator for percentages will be based on the number of participants included in 
the respective analysis set. 
Participants with missing data can generally be accounted for using the following approaches: 
• For summaries of demographics and Baseline characteristics: summarize percentages based 
on all participants in the analysis set and include a “Missing” category (corresponding to 
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participants with missing data for the variable being summarized) as the last row in the list of 
categories being summarized.  
• For summaries of efficacy and safety variables, unless otherwise specified: summarize 
percentages based only on those participants with observed data for the variable being 
summarized. As the denominator may be different from the number of participants in the 
analysis set being considered, the denominator should be displayed in the table. The general 
format for displaying this will be “n/Nsub (%).” 
Unless otherwise noted, all percentages will be displayed to one decimal place. No percentage 
will be displayed for zero counts, and no decimal will be presented when the percentage is 100%.  
For the purpose of the tabulations the lower and upper confidence limits for the percentages will 
be truncated at 0 and 100% respectively. 
For PK concentrations, summary statistics will include geometric mean, geometric coefficient of 
variation (CV), 95% confidence intervals (CIs) for geometric mean, arithmetic mean, SD, 
median, minimum, and maximum. All summaries of PK variables will be based on the observed 
values. No imputation will be used. 
Decimal places for descriptive statistics will always apply the following rules: 
• “n” will be an integer; 
• Mean, SD, and median will use one additional decimal place compared to the original data; 
• CV [%] will be presented with one decimal place; 
• Minimum and maximum will have the same number of decimal places as the original value. 
Derived variables in general will display the mean, SD and median to 1 more decimal place than 
the variables used in the derivation. If the number of decimal places reported in the raw data is 
varied, then use either the maximum raw number of reported decimal places or 3, whichever is 
the lowest, as a guide for the descriptive statistics. 
Statistical test of secondary efficacy variable will be presented as p-values rounded to four 
decimal places. P-value less than 0.001 will be presented as “<0.001” and p-value greater than 
0.999 will be presented as “>0.999.” Statistical comparison will be one-sided and will be 
performed at the 0.025 level of significance. 
If no participants have data at a given time point, for example, then only n=0 will be presented. 
However, if n<3, present the n, minimum and maximum only. If n=3, n, mean, median, 
minimum and maximum will be presented only. The other descriptive statistics will be left blank 
Demographics and baseline characteristics will be analyzed in the mITT population. Prior and 
Concomitant medications will be done in the SS. Efficacy analyses will be done in the mITT 
population. Safety, PK and PD analyses will be done respectively in the SS, PK-PPS and PD-
PPS. 
Once the last study participant has completed the SFU, or the last study participant has 
prematurely discontinued prior to reaching the SFU, the database will be locked. TFLs will be 
produced. 
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5.1.1 
General study level definitions 
5.1.1.1 
Analysis Time Points 
All data will be analyzed based on the visits identified per the Schedule of Activities in the 
protocol. Mapping to analysis visit windows is not applied, except for early termination visits 
(specified in Section 5.1.1.1.4). 
5.1.1.1.1 
Relative day 
Relative day will be provided in different listings and will be calculated as follows:  
− If the start (stop) date occurred on or after the first dose, but prior to the drug stop date, 
relative day is calculated as start (stop) date minus first dose date + 1 (the day of first 
dose will be Day 1).  
− If the start (stop) date occurred before the first dose, the relative day is calculated as date 
of first dose of investigational medicinal product (IMP) minus the start (stop) date (the 
day prior to first dose will be Day -1)  
− If the start (stop) date occurred after the last dose of IMP, the relative day to the most 
recent dose is calculated as start (stop) date minus last dose of investigational medicinal 
product (IMP) including a ‘+’to denote post treatment days (e.g. the day after last dose 
will be Day +1).  
Relative day will only be computed for fully completed dates and will be missing for partial 
dates. In such cases, relative day should be presented as ‘- -’ in the participant data listings. 
Relative day will be calculated from first dose of IMP 
5.1.1.1.2 
End date of the Treatment Periods 
Each of the study periods is constituted of a treatment period.  
The end date of the treatment period of each study period will be either the date of the last 
planned visit (Week 12 for the Main Treatment Period or the every 12 Weeks visit for the 
Extension Treatment Period) or the date of the Withdrawal visit (Early Withdrawal during the 
Main Treatment Period or Withdrawal Visit during the Extension Treatment Period) for 
participants who discontinued. If a participant does not have the last planned visit or Withdrawal 
visit, then either the date of the last scheduled (on site or phone call visits) or unscheduled visit 
during the considered period or the date of the last known dose of study drug during the 
considered period, whichever is later, will define the end date of the Treatment period. 
5.1.1.1.3 
Study periods 
Based on the specific requirements of safety and efficacy analyses, one concept of the definition 
of periods need to be considered for the study, which will be defined in detail in the section 
below. 
5.1.1.1.3.1 
Study periods for safety and efficacy data 
• Two study periods are included in this study, the Main Treatment Period and the Extension 
Treatment Period.  
No efficacy data are collected during the Extension Treatment Period thus, for efficacy analyses, 
only the Main Treatment Period will be considered.  
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The safety analyses will be performed on the Main Treatment Period as well as on the Overall 
Treatment Period. The Overall Treatment Period is constituted of the Main Treatment Period and 
of the Extension Treatment Period. The following definitions for completing study periods will 
be applied: 
• A participant is considered to have completed the Main Treatment Period if he/she completed 
the Week 12 visit and: 
− Decided to enter the Extension Treatment Period. 
OR 
− Transitioned to commercially available ZLP directly after the Week 12 visit (no 
Withdrawal or SFU visit required). 
OR 
− Decided not to enter the Extension Treatment Period and completed a SFU visit. 
• A participant is considered to have completed the study if he/she completed the Main 
Treatment Period and: 
− Did not enter the Extension Treatment Period. 
OR 
− Entered the Extension Treatment Period and: 
◦ 
withdrew from the Extension Treatment Period, discontinued ZLP, and completed the 
Withdrawal and SFU Visits. 
OR 
◦ 
transitioned to commercially available ZLP and completed the Withdrawal Visit. No 
SFU Visit is required. 
The total duration of study participation in the Main Treatment Period for all participants will be 
up to approximately 20 or 26 weeks, including the following periods:  
• Screening Period: 2 to 8 weeks 
• Treatment Period: 12-weeks  
• SFU Period: 40 days (after the last dose for patients who do not enter the extension period or 
do not transition to commercially available ZLP directly after the Week 12 visit). 
The Extension Treatment Period is constituted of the following periods: 
• Treatment period 
• SFU period: 40 days, for participants that withdrew from the Extension Treatment Period  
The end of the study is defined as the date of the last visit of the last participant in the study. 
The following definitions for starting and entering the periods will be applied: 
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• Treatment period starts with the first day of IMP and ends at the end date of treatment period 
defined in Section 5.1.1.1.2. All participants in the Safety Set will be considered to have 
started the Treatment period of the Main Treatment Period.  
• Follow-up period starts one day after the end of the Treatment period and ends after the final 
assessments on the SFU visit.  
5.1.1.1.4 
Mapping of assessments performed at (Early) Withdrawal Visit 
If a participant prematurely discontinues study drug at any time prior to Week 12 during the 
Main Treatment Period, the participant should return to clinic for a stand-alone EW Visit. If a 
participant withdrew during the Extension Treatment Period, the participant should perform a 
Withdrawal Visit. These assessments will be mapped to the next scheduled visit where each 
assessment is evaluated as per protocol. This approach means that there is a chance that EW (or 
Withdrawal) data will be mapped to different visits according to the schedule of assessments.  
 
5.1.1.1.5 
Definition of Baseline values 
Unless otherwise specified, Baseline will be the last available pre-dose value prior to the first 
injection of IMP in the Main Treatment Period, or if missing, the Screening value. Scheduled or 
unscheduled measurements can be used as the Baseline value. If a Baseline measurement is not 
available but an unscheduled measurement occurs after the planned baseline measurement time 
point but before dosing, then the unscheduled measurement will be used. 
Change from Baseline (CFB) is defined as the value minus baseline value. Percent Change from 
Baseline is defined as 100 x (Change from Baseline/Baseline). 
5.1.1.2 
Protocol Deviations 
Analyses related to protocol deviations are given in Appendix 6.1.2. 
5.1.1.3 
Treatment assignment and treatment groups 
Treatment group will be shown as: Zilucoplan 0.3mg/kg. 
5.1.1.4 
Center pooling strategy 
It is planned to recruit study participants in different sites in North America in this study. The 
data from all sites will be pooled for analyses. 
5.1.1.5 
Coding dictionaries 
Adverse events (AEs) and medical histories will be coded using version 24.0 or later of the 
Medical Dictionary for Regulatory Activities (MedDRA®).  
Medications will be coded according to version March 2021 or later of the World Health 
Organization Drug Dictionary (WHODD). 
5.1.1.6 
Multicenter studies 
Individual center results will not be displayed. 
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5.1.1.7 
Missing data 
5.1.1.7.1 
Efficacy endpoints 
For secondary efficacy analyses, missing data will be handled according to the secondary 
efficacy estimand definition: 
• For missing data of participants that discontinue from the study, a missing at random 
assumption will be used for imputation. This is in relation to the assumption that the 
participant had remained on their treatment throughout the study. 
• For other missing data, the same missing at random assumption as the one used for imputing 
missing data of participants that discontinue from the study will be applied. 
5.1.1.7.2 
Safety, PK and PD endpoints 
Missing data for Safety, PK and PD endpoints will not be imputed; observed cases will be used. 
This will include observations occurring after a participant receives rescue-medication. 
5.1.1.7.3 
Missing data due to COVID-19 
Missing data is expected to be one of the major implications of the COVID-19 pandemic. The 
following approaches/strategies will be applied to assess the impact of COVID-19 in this study.  
• Added an electronic Case Report form (eCRF) page “COVID-19 Impact”, including 
impacted visits, impacted assessments and reason why these assessments were impacted  
• Protocol deviations related to COVID-19 will be documented (in listings only). 
5.1.1.8 
Handling of repeated and unscheduled measurements 
All repeated and unscheduled measurements will be presented in the listings, where applicable. 
The following general rules will apply to all repeated and unscheduled measurements: 
• For repeated or unscheduled measurements obtained prior to the first dose of IMP the latest 
reliable value (scheduled or unscheduled) will be used in the calculation of descriptive 
statistics (i.e., Screening and/or Baseline) as defined in Section 5.1.1.1.5.  
• For repeated or unscheduled measurements obtained at Day 1 and prior to the first dose of 
IMP, the latest reliable value (scheduled or unscheduled) will be defined as the Baseline; 
• For repeated or unscheduled measurements obtained at any time point after the first dose of 
IMP, the original values (if non-missing) will be used in the calculation of changes from 
Baseline and for the descriptive statistics (i.e., in summaries by time point).  
5.1.1.9 
Handling of rescue therapy visits 
All rescue therapy visits will be presented in the listings, where applicable. However, the rescue 
therapy visits will not be presented for descriptive statistics (i.e., summaries by time point). The 
statistical analyses will present summaries at each scheduled visit. 
5.1.1.10 
Handling of missing dates and times 
Partially or completely missing dates may be imputed for the following reasons: 
• Classification of AEs as TEAEs; 
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• Classification of medications as past, prior, baseline or concomitant medications; 
• Duration of AEs  
Imputed dates will not be shown in listings. All dates will be displayed as reported in the 
database. 
The following rules will be applied for partially or completely missing start dates: 
• If year, month and day are all missing then assign the date of first dose of IMP. If an imputed 
start date is after the specified end date, then assign January 01 of the year of the end date, or 
the date of screening if this is later (if the latter imputation results in an end date that is 
earlier than the start date, then use January 01). 
• If month and day are missing, and year is: 
− the same as the year of the first dose of IMP then assign the month-day of first dose of 
IMP. If the imputed start date is after the specified end date, then assign January 01, or 
the month-day of screening date if this is later (if the latter imputation results in an end 
date that is earlier than the start date, then assign January 01); 
− not the same as the year of the first dose of IMP then assign January 01. 
• If only day is missing, and month-year is: 
− the same as the month-year of the first dose of IMP then assign the day of first dose of 
IMP. If the imputed start date is after the specified end date, then assign first day of the 
month, or the day of screening date if this is later (if the latter imputation results in an end 
date that is earlier than the start date, then assign first day of the month); 
− not the same as the month-year of the first dose of IMP then assign the first day of the 
month. 
The following rules will be applied for partial stop dates: 
• If only the month and year are specified, then use the last day of the month; 
• If only the year is specified, then use December 31 of the known year; 
• If the stop date is completely unknown, then use discharge date or data cut-off date. 
Note: Discharge date refers to the date of the end of study visit for completed participants or for 
participants that were withdrawn. For any AEs with known start date after the date of 
discontinuation, the date of last contact will be used as the discharge date. For participants still 
ongoing in the study at the time of the data cut-off, and for whom no discharge date is available, 
the date of the data cut-off will be used instead of the discharge date. 
In the event of ambiguity or incomplete data which makes it impossible to determine whether a 
medication was concomitant or not, the medication will be considered as concomitant. Any 
medication with a start date on the first dosing date, will be assumed to be concomitant. In the 
event of ambiguity or incomplete data which makes it impossible to determine whether an 
adverse event was treatment-emergent or not, the adverse event will be considered as treatment-
emergent. 
Imputed AE dates will be used for the calculation of duration of AEs, defined as: 
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Duration of AE = stop date – start date + 1. 
5.2 
Participant Dispositions 
The following summaries will be created. 
• Reasons for screen failures will be summarized using the ES.  
• Disposition of analysis sets will be summarized overall, by analysis sets (ES, ITT, mITT, 
SS, PK-PPS, PD-PPS). Percentages will be based on the number of participants in the ES 
overall. Disposition of analysis sets will also be summarized in the ES by region, with 
number of sites, principal investigator name, dates of first participant in and last participant 
out as well as the number of participants screened/screen failures. 
• Disposition and discontinuation reasons using mITT population will contain the number 
and percentage of study participants who started, completed, permanently discontinued the 
Main Treatment Period with primary reason of discontinuation, and entered, completed, 
permanently discontinued the Extension Treatment Period with primary reason of 
discontinuation. Percentages will be based on the number of participants in the mITT 
population. This summary will be performed for the Main Treatment Period as well as for the 
Overall Treatment Period. The disposition and discontinuation reasons will be duplicate in 
the ES in case there is a difference of strictly more than 5 patients between the ES and the 
ITT. 
• Discontinuation due to AEs using mITT population will summarize the total number of 
study participants who discontinued the study due to AEs by the categories: AE, serious fatal, 
and AE, non-fatal. This summary will be performed for the Main Treatment Period as well as 
for the Overall Treatment Period. The discontinuation due to AEs will be duplicate in the ES 
in case there is a difference of strictly more than 5 patients between the ES and the ITT. 
• Impact of COVID-19 using the mITT will summarize number and percentage of 
participants in each impact category by visit. This table will be done overall. Visits and 
assessments done via video calls will be listed. For both the listing and the summary table, 
only visits at which efficacy or safety assessments are scheduled will be included. This 
summary will be performed for the Main Treatment Period as well as for the Overall 
Treatment Period. The impact of COVID-19 will be duplicate in the ES in case there is a 
difference of strictly more than 5 patients between the ES and the mITT. 
Listings of study participant disposition and study discontinuation, analysis set and study 
participants who did not meet study eligibility criteria will be provided. Listing of all participants 
impacted by COVID-19 will also be provided.  
5.3 
Planned efficacy/outcome analyses 
5.3.1 
Secondary efficacy estimand/secondary endpoint analyses 
5.3.1.1 
Main secondary efficacy endpoint 
5.3.1.1.1 
Definition of endpoint 
The secondary efficacy endpoint is the CFB in Week 12 in MG-ADL Score. The complete list of 
MG-ADL items and scores and calculation of total score are provided in Appendix 6.1.5.1. The 
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total score collected at each post baseline visit will be used to calculate change from Baseline, in 
summaries and for efficacy analyses. 
5.3.1.1.2 
Main analytical approach 
For the efficacy endpoint, the CFB to Week 12 in MG-ADL score will be modeled using a mixed 
model for repeated measures (MMRM) with baseline MG-ADL Score and Week 1, 2, 4, 8 and 
12 as fixed factors and baseline MG-ADL Score by visit as interaction term. The Least square 
mean (LSM) followed by the 95% Confidence Interval (CI) and standard error of the 
corresponding CFB at each visit will be reported. 
An one-sample t-test will be used to compare the LSM of the CFB to Week 12 in MG-ADL 
score to a NI margin. The NI margin being investigated is a clinically relevant 2-point increase 
(worsening) at Week 12. The Week 12 CFB will be compared to 2 at a 1-sided α=0.025 level for 
the mITT Population. The p-value associated to this test will be reported. The NI of Week 12 
MG-ADL over the Baseline MG-ADL, will be shown if the upper limit of the one sided 97.5% 
CI (or the two sided 95% CI) of the LSM MG-ADL CFB at Week 12 does not cross the non 
inferiority margin of 2 points (Food and Drug Administration, 2016). 
A separate one sample t-test for the CFB will be employed based on the observed data setting the 
Week 12 MG-ADL score as the worst score though all the study visits for participants 
experienced ICE1 or ICE2; this analysis will serve as sensitivity analysis. 
CFB in MG-ADL score will be summarized by visit using descriptive statistics in the mITT. 
CFB MG-ADL will be listed for all participants of the mITT. For participants infected with 
COVID-19 as per the AE page, CFB in MG-ADL will be listed by visit separately. 
A listing of all the intercurrent events will be provided. 
5.3.1.1.3 
Handling of missing data 
The number of missing values by visit for the main secondary efficacy endpoint will be provided 
using descriptive statistics on the mITT. Additionally, the number of missing values by visit due 
to COVID-19 will be summarized for the main secondary efficacy endpoint (using the “COVID-
19 Impact” e-CRF page) as explained in Section 5.2.  
For secondary efficacy analyses, missing data will be handled according to the secondary 
efficacy estimand definition: 
• For missing data of participants that discontinue from the study, a missing at random 
assumption will be used for imputation. 
• For other missing data, the same missing at random assumption as the one used for imputing 
missing data of participants that discontinue from the study will be applied. 
The MMRM that will be used to model the CFB to Week 12 in MG-ADL score consider missing 
data with the missing at random assumption. 
5.3.1.1.4 
Sensitivity analysis 
The one-sample t-test will be applied on the observed data at Week 12. 
A one-sample Wilcoxon Signed Rank Test will also be applied on the observed data at Week 12, 
with Worst observation carried forward between baseline and all post baseline visits. 
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5.3.1.2 
Additional secondary efficacy endpoint 
5.3.1.2.1 
Definition of endpoint 
The additional secondary efficacy endpoint is the CFB in Week 12 in QMG Score. More details 
on how these scores are calculated can be found respectively in Section 6.1.5.2. 
5.3.1.2.2 
Main analytical approach 
For the additional secondary efficacy endpoint, the same strategy (main analytical approach in 
Section 5.3.1.1.2 and handling of missing data in Section 5.3.1.1.3) will be applied. 
No statistical test will be performed for the additional secondary efficacy endpoint. 
5.3.2 
Other efficacy endpoint analyses 
The other efficacy endpoints are: 
• Time to first receipt of rescue therapy over the Main Treatment Period 
• Change in SoC therapy medication dose regimen for gMG during the Main Treatment Period 
• Achievement of Minimal Manifestation Status per MGFA PIS at Week 12 without rescue 
therapy 
• Achieving MSE, defined as an MG ADL of 0 or 1 at Week 12 without rescue therapy 
• CFB to Week 12 in QMG subscores: ocular, bulbar, respiratory, limb 
• CFB to Week 12 in MG-QOL15r score 
• MG-ADL score responder rate (responder is defined as achieving ≥ 3-point improvement 
from Baseline [decrease] at Week 12 and not having taken rescue therapy) 
• QMG score responder rate (responder is defined as achieving ≥5-point improvement from 
Baseline [decrease] at Week 12 and not having taken rescue therapy) 
The MG-ADL score responder rate will be assessed based only on participants having an MG-
ADL score ≥ 3 at Baseline, while the QMG score responder rate will be assessed based only on 
participants having an QMG score ≥ 5 at Baseline. 
All those endpoints will be analyzed using descriptive statistics, as mentioned in the Section 5.1. 
The time to first receipt of rescue therapy over the Main Treatment Period and over the Overall 
Treatment Period will be analyzed as time-to-event, using Kaplan-Meier plots. 
For the MG-ADL and QMG responder rate the number and percentage of participants who have 
a reduction (i.e., improvement) of ≥ X will be summarized in the mITT at Week 12. The 
improvement values will start at the maximum level of worsening and will continue to the 
maximum level of improvement seen in the study. Note this is an extension of the “Achieving a 
≥3-point reduction in MG-ADL Score at Week 12 without rescue therapy” and “Achieving a ≥5-
point reduction in QMG Score at Week 12 without rescue therapy” endpoints.  
Individual line plots with individual values of Total MG-ADL, QMG and MG-QoL15r scores 
will be created in mITT. 
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For participants infected with COVID-19 as per the AE page, CFB in QMG and MG-QOL15r 
score will be listed by visit separately. 
5.4 
Planned safety and other analyses 
Safety analyses will be presented on the SS. Listings for all safety analyses will be presented. 
5.4.1 
Extent of Exposure 
IMP duration will be summarized. The number of days on IMP will be calculated as follows: 
IMP duration = [(Date of Last Dose Received) -(Date of First Dose Received)] +1 
The exposure duration (i.e., total time at risk that incorporates 5 half-lives of ZLP) is defined as: 
Exposure duration (in days) = [min (Last dose + 40 days, Last Visit/Contact) - (Date of First 
Dose Received)] +1 
Patient-years exposure (PEY) will be calculated as the sum of the exposure durations of all study 
participants divided by 365.25. 
The overall extent of exposure in the SS will be summarized during the Main Treatment Period 
and in the Overall Treatment Period. 
Note that temporary drug discontinuations and missed doses will not be incorporated into the 
calculations of the extent of study drug exposure analyses. 
The number of doses missed (from the eCRF Study drug administration page after Day 1) will be 
summarized cumulatively. The missed doses will be derived based on the expected number of 
daily doses the participant should receive within a defined period minus the total number of 
doses he/she has received during that period. For this derivation, the number of total syringes 
administered to a participant at each visit will be considered via the total number of kits 
administered at each visit, assuming that each kit contains 7 syringes to be used for 7 daily doses.  
In addition to the assessment of study medication duration as a continuous variable, the number 
and percent of study participants with treatment duration meeting the following criteria will also 
be summarized: 
• ≥ 1 day  
• ≥ 8 days  
• ≥ 15 days  
• ≥ 29 days  
• ≥ 57 days 
• ≥ 84 days 
All drug administration details will be listed. 
The compliance between two in-clinic visits, as well as the overall compliance will be described. 
The study withdrawal will be summarized over the Main Treatment Period and over the Overall 
Treatment Period time-to-event, using Kaplan-Meier plot. 
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For the Main Treatment Period, time to IMP discontinuation is defined as: Date of last IMP dose 
– date of first IMP dose + 1. Participants that did not early withdraw should be censored at the 
date of Main Treatment Period completion. 
For the Overall Treatment Period, time to IMP discontinuation is defined as: Date of last IMP 
dose – date of first IMP in Main Treatment Period + 1. Participants that did not (early) withdraw 
should be censored at the date of their last contact.  
For the Extension Treatment Period, time to IMP discontinuation is defined as: Date of last IMP 
dose – date of first IMP in Extension Treatment Period+ 1. Participants that did not withdraw 
should be censored at the date of their last contact.  
For all treatment periods, participants that switch to commercially available Zilucoplan are not 
considered as discontinuation events; for the time to event analysis exposure will be censored at 
the date of their last contact. 
5.4.2 
Adverse Events 
5.4.2.1 
Data considerations 
Pre-existing conditions that are detected prior to administration of the first dose of study drug 
will be recorded as part of the medical history. For all subjects, the AE and SAE reporting period 
will start with the signature of the ICF and will end with the last study visit (i.e., SFU, Week 12 
Visit). 
In addition, AEs will be classified for severity according to the Common Terminology Criteria 
for Adverse Events (CTCAE) Version 5 or later (United States Department of Health and Human 
Services, Version 5.0, November 17, 2017). For any AEs where it is not possible to provide a 
CTCAE grading, the events will be assessed using a standard intensity classification (mild, 
moderate and severe). These will be tabulated together with the AEs that were not classified 
according to CTCAE criteria i.e., all Grade 1 AEs as per CTCAE criteria will be included in the 
‘mild’ category together with those AEs classified as mild as per the ‘standard’ intensity 
classification. 
The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each 
AE based on this general guideline:   
• Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.   
• Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living.   
Note: instrumental activity of daily living refers to preparing meals, shopping for 
groceries or clothes, using the telephone, managing money, etc. 
• Grade 3 Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self care 
activities of daily living. 
Note: self care activities of daily living refer to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden 
• Grade 4 Life-threatening consequences; urgent intervention indicated.   
• Grade 5 Death related to AE. 
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For the purpose of the tabulations AE intensity categories will be mapped to CTCAE severity 
classifications grade 1 to 5 as described below: 
• Mild – Grade 1 
• Moderate – Grade 2 
• Severe – Grade 3, 4, 5, where 
− Grade 4 will be derived from the SAE monitoring form, when SAE is life threatening. 
− Grade 5 will be derived from the SAE monitoring form when SAE is fatal. 
A TEAE is defined as an AE starting on or after the time of first administration of IMP and up to 
and including 40 days after the final dose (or last contact depending on which occurs first). 
Adverse events starting before the date of the first administration of IMP will not be considered 
TEAEs. 
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent 
unless evidence exists that does not allow the AE to be treatment-emergent. Handling of missing 
dates for classification of AEs as TEAEs is described in Section 5.1.1.10.  
A TEAE will be counted as a TEAE related to IMP if the response to the question “Relationship 
to Study Medication” is “Related”.  
Severe TEAEs are those with CTCAE Grade 3 or above, or those without a CTCAE grading 
classified as ‘severe’ by the Investigator. 
AEs will be presented as “number of participants (percentage of participants) [number of 
events]”. In this style of output, “[number of events]” will include all cases of an AE including 
repeat occurrences in individual participants, while “number of participants” will count each 
participant only once. 
5.4.2.2 
AE summaries 
1. A TEAE overview table will be provided by treatment group, including the number, 
percentage of participants and frequency of the following TEAEs: 
− Any TEAEs 
− Any TEAEs above 5% of occurrence 
− Serious TEAEs  
− TEAEs leading to permanent withdrawal from IMP 
− Treatment-related TEAEs  
− Severe TEAEs  
− TEAEs leading to death 
− All deaths (AEs leading to death) 
2. The number, percentage of participants and frequency of the following TEAEs will be 
summarized by System Organ Class (SOC), high level term (HLT), and PT: 
− Serious TEAEs 
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− Non-serious TEAEs 
− TEAEs leading to death 
In case of 5 or less of the following TEAEs, no summary table will be displayed, and the listing 
of AEs will be used. In case of 6 events or more the number, percentage of participants and 
frequency of the following TEAEs will be summarized by System Organ Class (SOC), high level 
term (HLT), and PT: 
− Any TEAEs  
− Severe TEAEs 
− TEAEs leading to permanent withdrawal from IMP 
− Treatment-related TEAEs leading to permanent withdrawal from IMP 
3. The number, percentage of participants with TEAEs will be summarized by maximum 
intensity (mild, moderate and severe), SOC, and PT as well as by intensity (mild, moderate 
and severe), SOC, and PT. 
4. The number, percentage of participants and frequency of the following TEAEs will be 
summarized by relationship, SOC, HLT, and PT: 
− Any TEAEs 
− Serious TEAEs 
− Fatal TEAEs 
For these summaries, the number and percentage of participants who experienced at least one 
TEAE as well as the number and percentage of participants who experienced each specific SOC, 
HLT (if HLT is presented) and PT will be presented. The corresponding number of TEAEs will 
also be presented for the Overall Summary of TEAEs table. For the presentation of TEAE 
incidences, the SOCs will be sorted alphabetically, and HLT within SOC – (if HLT is presented), 
and within HLT, the PT will be used and presented by decreasing total frequency. 
Listings of all AEs in (ES), permanent withdrawal of IMP due to AEs, participant 
discontinuation from study due to AEs, AEs leading to death will be presented by participants in 
SS. 
To assess the impact of the COVID-19 pandemic on safety, additional summaries and listings 
will be presented. All COVID-19 related TEAEs will be summarized by MedDRA SOC, HLT 
and PT.  
Study participants with a confirmed or suspected COVID-19 infection were identified by 
searching TEAEs for selected MedDRA terms as defined in Section 6.1.9 and described as 
“COVID-19 related TEAEs. 
A separate listing of all COVID-19 related AEs will be presented in SS. 
In addition, all listing of AEs will include a column for COVID-19 relatedness. 
Since the beginning of the COVID-19 pandemic, the COVID-19 vaccination followed a specific 
mass vaccination program in a short time frame. Administration of doses of COVID-19 
vaccination might be needed during this study and is likely to increase the reporting of AEs. 
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Vaccination might have an impact on the safety reporting in the non-COVID-19 vaccine clinical 
trials. Due to this, the potential impact of concomitant COVID-19 vaccination on the current trial 
may be different from other types of concomitant drugs and established vaccination, due to the 
frequency of potential events related to the COVID-19 vaccination and the evolving safety 
profile of these new vaccines. To control the potential bias arising when an important proportion 
of the vaccinated participants reported AEs to vaccination (which inappropriately may be 
captured as adverse reactions in the product information) additional safety outputs within the 
frame of sensitivity analysis will be created. 
Additional sensitivity safety analysis with outputs presenting the TEAEs occurred when 
participants were considered as not at risk of TEAEs related to COVID-19 vaccination is 
proposed. The approach of interval censoring will be employed: interval censoring between 
COVID-19 vaccination date and a pre-specified period in which participants are considered as at 
risk for COVID-19 vaccination related AEs. A 7-day period may allow the removal of the 
potentially most frequently reported AEs related to COVID-19 vaccines. In such outputs, all 
TEAE data will be included, with the exception of the events occurred within the defined 
window of 7 days post COVID-19 vaccination(s) for those participants vaccinated during the 
study and all TEAE data for those participants not vaccinated during the study. 
All AEs within a 7-day period post each COVID-19 vaccination will be summarized for all 
vaccinated participants. Two separate listings will display the AEs after adjustment of the 
interval censoring and the concomitant COVID-19 vaccination. 
All AEs after a 7-day period of each COVID-19 vaccination will be listed for all vaccinated 
participants. Two separate listings will display the AEs after adjustment of the interval censoring 
and the concomitant COVID-19 vaccination. 
At all the outputs referring to the interval vaccination censoring, the following footnote will be 
incorporated: “COVID-19 Vaccination Interval Censored (TE)AEs exclude those (TE)AEs 
occurred within the pre-specified time period of 7 days post COVID-19 vaccination(s) for each 
participant, if applicable.” 
5.4.3 
Other Safety Assessments 
Other safety assessments (AE of special interest, Laboratory data and Vital Signs) will also be 
performed in the SS.  
5.4.3.1 
AEs of Special Interest and AEs of Interest 
The AEs of Special Interest identified in this study are the Hy's Law that are described in 
Section 5.4.3.2.4. 
The following are AEs of Interest (as defined in Section 6.1.6 that require special statistical 
analyses:  
− Hypersensitivity reactions  
−  Anaphylactic reactions 
− Injection site reactions 
− Drug related hepatic disorders 
− Malignancies or unspecified tumors 
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The number and percentage of participants who experience each AE of Interest will be 
summarized separately for each AE of interest. The following summaries will be presented: 
− Incidence of AEIs and serious AEIs by SOC and PT (serious and non-serious will appear 
in the same table) 
− Incidence of AEIs by relationship, SOC and PT 
− Incidence of AEIs by maximum intensity (mild, moderate and severe), SOC and PT. 
5.4.3.2 
Clinical laboratory evaluations 
The following table (Table 5.1) lists hematology, chemistry and coagulation analytes that are 
collected throughout the study, using a central laboratory and following the schedule of 
assessments according to the protocol. 
Table 5.1: 
Protocol-required safety laboratory assessments 
Laboratory 
assessments 
Parameters 
Hematology 
Platelet count 
RBC indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with 
differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC count 
Hemoglobin 
Hematocrit 
Clinical chemistrya 
BUN 
Potassium 
AST/SGOT 
Total and direct bilirubin 
 
Creatinine 
Sodium 
ALT/SGPT 
Total protein 
 
Glucose 
Calcium 
Alkaline phosphatase 
Amylase 
 
Lipase 
 
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 women of 
non-childbearing potential only) 
• 
Serum hCG pregnancy test (as needed for women of childbearing potential) b 
The results of each test must be entered into the eCRF. 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; eCRF=electronic 
Case Report form; HBsAg=hepatitis B surface antigen; hCG=human chorionic gonadotropin; 
INR=international normalized ratio; IRB=Institutional Review Board; MCH=mean corpuscular hemoglobin; 
MCV=mean corpuscular volume; RBC=red blood cell; SAE=serious adverse event; SGOT=serum glutamic-
oxaloacetic transaminase; SGPT=serum glutamic-pyruvic transaminase; ULN=upper limit of normal; 
WBC=white blood cell 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in the protocol. All events of ALT ≥3×ULN and bilirubin ≥2×ULN (>35% direct 
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Table 5.1: 
Protocol-required safety laboratory assessments 
Laboratory 
assessments 
Parameters 
bilirubin) or ALT ≥3×ULN and INR >1.5, if INR measured, may indicate severe liver injury (possible Hy’s 
Law) and must be reported as an SAE (excluding studies of hepatic impairment or cirrhosis). 
b Local urine testing will be performed at visits subsequent to the Screening Visit. 
All laboratory samples are collected prior to IMP administration at applicable visits. 
5.4.3.2.1 
Laboratory values over time 
Chemistry, hematology and quantitative urinalysis (observed value, absolute change from 
Baseline) will be summarized in standard units using descriptive statistics at each scheduled 
visit. Qualitative urinalysis results will be summarized in frequency tables for each visit. 
The central data will be used for the summary tables. If multiple central lab data were captured at 
scheduled visits, the average would be used for continuous values, or the worst will be used for 
categorical values. 
Measurements Below the Limit of Quantification (BLQ) will be imputed with half of the lower 
limit of quantification Lower Limit of Quantification (LLOQ), and measurements Above the 
Limit of Quantification (ALQ) will be imputed to the upper quantification limit for the purpose 
of quantitative summaries. 
All laboratory test results will be listed, including Baseline, scheduled and unscheduled visits 
with results in standard unit. Values outside the reference range for the continuous variables will 
be flagged in the listings. The reference ranges will also be reported in the listings. Additional 
lab test, including pregnancy testing, will also be listed. 
5.4.3.2.2 
Individual Subject Changes of Laboratory Values 
The laboratory variables that are categorized as normal, high or low based on the reference range 
supplied by the analytical laboratory will be presented in shift tables from Baseline to each 
scheduled post-Baseline visit and any post-Baseline visit (including unscheduled visits). 
5.4.3.2.3 
Laboratory Marked abnormalities 
Treatment-emergent marked abnormalities (TEMAs) in laboratory parameters will be 
summarized at each scheduled visit and at any visit (including unscheduled visit). Thresholds for 
defining marked abnormalities for relevant laboratory parameters are available in Appendix 
6.2.Treatment-emergent is defined as meeting the MA criteria at any post-Baseline visit while 
the MA criteria are not present before dosing. 
Listings will include a flag for values identified as TEMA. 
5.4.3.2.4 
Assessment of potential liver toxicity 
To assess the potential for liver toxicities, the following criteria will be used to define levels of 
liver function tests (LFT) elevation: 
• AST: ≥ 3 x ULN, ≥ 5 x ULN, ≥ 8 x ULN, ≥ 10 x ULN, ≥ 20 x ULN 
• ALT: ≥ 3 x ULN, ≥ 5 x ULN, ≥ 8 x ULN, ≥ 10 x ULN, ≥ 20 x ULN 
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• 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 
• ALP: ≥ 1.5 x ULN 
Hepatic events will be defined as: 
• TEAEs with narrow Standardised MedDRA Queries (SMQ) of “Drug related hepatic 
disorders - comprehensive search (SMQ)”. However, these 2 sub-SMQs are to be excluded: 
“Liver neoplasms, benign (incl cysts and polyps) (SMQ)” and “Liver neoplasms, malignant 
and unspecified (SMQ)”. 
The following laboratory criteria for potential drug induced liver injuries are defined as follows: 
• AST or ALT ≥ 3xULN with TBL ≥ 1.5xULN 
• AST or ALT ≥ 3xULN with TBL ≥ 2xULN 
• AST or ALT ≥ 3xULN with INR>1.5 (if INR is measured) 
In addition, post-baseline potential Hy’s Law cases will be identified using the following 
definition: 
• either AST or ALT ≥ 3×ULN with concurrent ALP < 2 × ULN and concurrent total bilirubin 
≥ 2×ULN  
In order to meet the above criteria, a study participant must experience the elevation in Bilirubin 
and ALT and AST (and the absence of the ALP elevation) at the same date. For example, a study 
participant who experiences a > 2xULN elevation of bilirubin at one date and a > 3xULN 
elevation in ALT (or AST) at a subsequent visit date has not fulfilled the Hy’s law criteria. 
The number and percentage of study participants with elevated liver function tests will be 
presented at any visit (including unscheduled visits) in the SS. The number and percentage of 
study participants with potential drug induced liver injuries including those who potentially meet 
the Hy’s law criteria and Drug related hepatic disorders TEAEs will be summarized. The liver 
function results for study participants with elevated liver function results will be listed. 
Scatterplots for each liver function test will be presented to show the shifts from Baseline to the 
maximum post-Baseline result. The ULN of concern (i.e., 3xULN for ALT or AST, and 2xULN 
for TBL or ALP) will also be presented as lines on the plots. In addition, a scatterplot of the 
maximum post-Baseline TBL (/ULN) versus the maximum post-Baseline ALT (/ULN) will be 
provided on a logscale. Reference lines of 3ULN for ALT and 2ULN for TBL will be presented 
on the graph. If any study participant meets the potential Hy’s law criteria, a graph displaying 
each liver function test (expressed as X ULN on a logscale) by time will be presented for each 
identified case. 
5.4.3.2.5 
Analysis of Lipase, Amylase, and Eosinophils 
Laboratory values (including corresponding normal ranges) will be used for shift tables/figures, 
patient profiles and aggregated plots. 
Tables summarizing shifts from baseline to maximum post-baseline CTCAE for increase in 
lipase and amylase will be presented. The grades to be used for amylase and lipase are defined 
by CTCAE Version 5.0 as follows: 
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• Grade 0: ≤ ULN 
• Grade 1: > ULN – 1.5 x ULN 
• Grade 2: > 1.5 – 2.0 x ULN 
• Grade 3: > 2.0 – 5.0 x ULN 
• Grade 4: ≥ 5.0 x ULN 
Grade 0 is not defined per NCI-CTCAE but will be used in derivations for simplicity to indicate 
that evaluable measurements are available. 
Tables summarizing shifts from baseline to maximum post-baseline result for increase in 
eosinophils will be described according to the categories low, normal, and high.  
The summary of these laboratory parameters will also include a “Missing” and “Total” category. 
The aggregated line plots will be presented for study participants with increase in lipase and 
amylase with Grade 1 and above (i.e., >ULN) and with high results in eosinophils. The line plots 
will be presented by laboratory parameter (amylase, lipase, eosinophils). 
5.4.3.3 
Vital Signs 
Vital signs (temperature, pulse rate, respiratory rate, and blood pressure) will be collected 
throughout the study. 
5.4.3.3.1 
Vital Sign Values Over Time 
Observed values and changes from Baseline will be summarized by vital sign variables and by 
scheduled visit. 
The number and percentage of participants who meet each of the marked abnormality criteria 
outlined in Appendix 6.2 will be summarized at each scheduled visit and at any visit (including 
unscheduled visit). 
Repeated and unscheduled measurements will be handled as described in Section 5.1.1.8. 
5.4.3.3.2 
Individual Subject Changes of Vital Sign Values 
The Vital Signs that are categorized as normal, high or low based on the reference will be 
presented in shift tables from Baseline to each scheduled post-Baseline visit and any post-
Baseline visit (including unscheduled visit). 
A by-participant listing of all vital sign measurements and change from Baseline will be 
presented. The listing will include a flag for values identified as markedly abnormal. 
5.4.3.4 
Electrocardiograms 
The following variables will be reported: 
• 
Heart rate (beats/min) 
• 
PR interval (ms) 
• 
RR interval (ms) 
• 
QRS duration (ms) 
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• 
QT interval (ms) 
• 
QT corrected for heart rate using Fridericia’s formula (QTcF = QT/RR1/3) (ms) 
5.4.3.4.1 
Electrocardiogram Values Over Time 
Observed values and changes from Baseline will be summarized at scheduled visit and by ECG 
variable. Baseline value will be based on the screening visit as ECG is not performed on Day 1. 
The number and percentage of participants who met each of the marked abnormality criteria 
outlined Section 6.2.3 will be summarized at each scheduled visit and at any visit (including 
unscheduled visit). 
5.4.3.4.2 
Individual Participant Changes of Electrocardiograms Values 
The number and percentage of participants with normal, abnormal not clinically significant and 
abnormal clinically significant, not evaluable and not done ECG results will be provided in a 
shift table from Baseline to worst post-Baseline interpretation during the study. 
A listing of electrocardiogram data will be presented, including repeated and unscheduled 
measurements. 
5.4.3.5 
Physical examination 
Results of clinically significant physical examination abnormalities were reported as adverse 
events. No additional listing will be provided. 
5.4.3.6 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
C-SSRS instrument recorded at screening visit references the lifetime period and the past six 
months period. Baseline to end of study visit summaries reference the period prior to the visit 
assessed. 
Results of the C-SSRS, as well as the treatment emergent item at Week 12 (or (early) withdrawal 
will be summarized in SS by scheduled timepoint using the number of participants and 
percentage with: 
1. suicidal ideation, 
2. suicidal behavior,  
3. suicidal ideation or behavior,  
4. self-injurious behavior without suicidal intent. 
Suicidal ideation is defined as an event in any of the following 5 categories: 
Suicidal behavior is defined as an event in any of the following 5 categories: 
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Suicidal behavior or ideation is defined as an event in any of the above 10 categories. 
Self-injurious behavior without suicidal intent is corresponding to the response to 
 in questionnaire. 
The treatment emergent item at Week 12 is defined as any item that is present at Week 12 that 
was not present at Baseline.  
A by- participant listing of the C-SSRS questionnaire data will be provided. 
5.5 
Other Analyses 
5.5.1 
Other endpoints and/or parameters 
5.5.1.1 
Pharmacokinetics 
The plasma concentrations of ZLP and its two major metabolites (
) will 
be summarized by scheduled sampling day for the PK-PPS using n, arithmetic mean, median, 
SD, minimum, maximum, geometric mean, geometric coefficient of variation (geoCV) and 95% 
Confidence Interval (CI) (assuming log-normally distributed data). 
PK summaries will be based on observed value. No imputation will be done. 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 individual data
points at a timepoint are above the LLOQ. Values that are BLQ will be replaced by the
numerical value of the LLOQ/2 in this instance.
•
The 95% CI lower and 95% CI upper should be left blank if the SD (or equivalently, the
geoCV) is 0
•
The geoCV will be calculated using the following formula where SD is the standard
deviation from the log-transformed data
geoCV(%) = √exp(SD2) −1 × 100.
Individual concentrations will be listed for the PK-PPS and will include the actual sampling time 
in days relative to the previous dose.  
PK assessments in participants undergoing rescue therapy will be analyzed separately. 
Plasma concentration data of Zilucoplan may be subjected to population pharmacokinetic 
analysis to derive population estimates of PK parameters and test the effect of various covariates 
such as age, weight, gender. Details of the analysis will be described in a separate Data Analysis 
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Plan (DAP). This analysis may be performed by combining the data from the current study with 
data from other Zilucoplan studies if deemed appropriate. The results of the population PK 
analysis will not be reported in the CSR but may be in a separate modelling report. 
5.5.1.2 
Pharmacodynamics 
Pharmacodynamic analyses will be performed on the PD-PPS. The pharmacodynamic endpoint 
is the sRBC lysis assay.  
Summary statistics will be provided for the values, change from baseline, and percent change 
from baseline at each of the scheduled assessment time points.  
PD assessments in participants undergoing rescue therapy will be analyzed separately. 
Population PD or population PK/PD analyses may be conducted for the PD variables of interest. 
Details of such PD or PK/PD analyses will be described in a separate DAP. The results of the 
analyses will not be reported in the CSR but may be in a separate report. 
5.5.1.3 
Time needed for administration of SC ZLP 
The time needed for administration of SC ZLP will be analyzed using descriptive statistics as 
detailed in Section 5.1. 
5.5.1.4 
Participants’ treatment satisfaction 
The participants’ treatment satisfaction is assessed via the TSQM-9 questionnaire. Descriptive 
analyses of the Effectiveness, Convenience and Global Satisfaction subscore will be displayed. 
Bar charts illustrating the mean and standard error at each visit by domain will be provided.  
Individual participant listings will be provided for all participants and for participants infected 
with COVID-19 as per the AE page. The details for the derivation of scores based on the TSQM-
9 questionnaire are available in Section 6.1.5.6. 
5.5.1.5 
Participants’ treatment preference 
The participants’ treatment preference is assessed via a single question where only one answer 
should be selected. If more than one answer is selected, the value will be set as Missing. 
Descriptive analyses, as detailed in Section 5.1, will be used to analyze the participants’ 
preference. 
5.5.1.6 
Genomics 
No Genomics analysis is planned in this study. 
5.6 
Subgroup analyses 
No subgroup analyses are planned in this study. 
5.7 
Interim Analyses 
If ZLP is not commercially available in the US at the time of the last visit of the last participant 
in the Main Treatment Period, an interim analysis will be conducted. This interim analysis will 
include all data collected during the Main Treatment Period. 
At the interim analysis, all TFLs concerning the Main Treatment Period only will be provided, 
unless otherwise stated. 
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If further interim analysis will be considered during the Main Treatment Period then this, will be 
of exploratory nature and only descriptive statistics will be provided. 
At the final analysis, all the TFLs concerning the Main Treatment Period and the Overall 
Treatment Period will be provided, except: 
- 
The by visits participant disposition and safety analyses will be displayed only on the 
Overall Treatment Period, 
- 
The participant disposition and safety listings will be provided on the Overall Treatment 
Period. 
5.8 
Data Monitoring Committee (DMC) or Other Review Board 
No DMC or Other review Board are planned in this study. 
 
6 
SUPPORTING DOCUMENTATION 
6.1 
Appendix 1 Non-key analysis specifications 
6.1.1 
Baseline characteristics and demographics 
Participant demographics and baseline characteristics will be summarized for the mITT, using 
descriptive statistics. In case there is a difference of more than 5 study participants, those 
descriptive statistics will be duplicated in the SS.  
Descriptive statistics for continuous variables (including n, mean, SD, Median, Min and Max) 
will be provided for: 
− Age (years), calculated as (year of informed consent date – year of birth  
− Height (cm) 
− Weight (kg) 
− Body mass index (BMI) (kg/m2) calculated as: 𝐵𝑀𝐼= 
Weight (kg)
(Height (m))2 using the weight and 
height measurements obtained at screening.  
− Baseline MG-ADL and QMG scores  
Descriptive statistics for categorial variables (including counts and percentages) will be provided 
for: 
− Gender (Male/Female) 
− Race (American Indian or Alaska native, Asian, Black, Native Hawaiian or other Pacific 
Islander, White, Other/Mixed) 
− Ethnicity (Hispanic or Latino, Not Hispanic or Latino)  
− Age (≤18, 19- <65 and ≥65 years). 
− Geographic region (North America)  
− Country 
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− BMI in kg/m2 (<18.5, 18.5 - <25, 25 - <30, 30 – <35, 35- < 40, ≥ 40) 
− Weight in Kg (<43, 43 - <56, 56-<77, 77 - <150, ≥ 150) 
− MD-ADL scores (≤9/≥10) 
− QMG scores (≤17 / ≥18) 
− Chronic Kidney Disease Stages: normal renal function (Estimate glomerular filtrate rate 
(eGFR) ≥ 90 mL/min/1.73m2), mild (eGFR 60–89 mL/min/1.73m2 [CKD stage 2]), 
moderate (eGFR 30–59 mL/min/1.73m2 [CKD stage 3]), severe (eGFR 15–29 
mL/min/1.73m2 [CKD stage 4]) renal insufficiency end stage renal disease: eGFR < 15 
mL/min/1.73m². A by-participant listing of Baseline characteristics will be provided. 
6.1.2 
Protocol deviations 
Important protocol deviations (IPDs) are deviations from the protocol which could potentially 
have a meaningful impact on the study conduct, on the primary analysis, key safety or PK/PD 
outcomes for an individual participant. IPDs will be identified and documented prior to data base 
lock to confirm exclusion from analysis sets. 
The summary of the IPDs will be performed for the Main Treatment Period as well as for the 
Overall Treatment Period in mITT. 
Relationship to COVID-19 will be programmed from the COVID-19 Impact eCRF page or when 
available, it will be assessed by the sites. 
A listing of the important protocol deviations will be provided for the Main Treatment Period as 
well as for the Overall Treatment Period in mITT population; a COVID-19 related flag will be 
present. 
6.1.3 
Medical history 
6.1.3.1 
Medical history (other than MG disease history) 
Medical History will be summarized by SOC, HLT and preferred term (PT) for the mITT 
population. A participant will be counted only once for each preferred term. The summary will 
present the results alphabetically by SOC, HLT within SOC, and within HLT, by decreasing 
frequency for the PT.  
Medical History will be listed on the ES population.  
6.1.3.2 
gMG disease history  
The following gMG disease history data will be summarized for the mITT Population. 
• Age at onset (years) 
• Duration of disease (years) = (Date of Study Day 1 – Date of Diagnosis)/365.25 
Note: If the Date of Diagnosis day and month are missing impute July 2nd, if only the day is 
missing impute the 15th. If the imputed Date of Diagnosis date is later than the date of Study 
Day 1, impute Study Day 1. 
• Symptoms at onset (Ocular/Generalized) 
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Note: Generalized symptoms at onset: participants with respiratory symptoms or symptoms 
in the limb, bulbar or any other location; participants at this category might also have ocular 
symptoms at onset as well. 
• MGFA Disease Class at Screening (Class II (IIa, IIb), III (IIIa, IIIb), or IV (IVa or IVb)) 
• Ever had a Crisis (Yes/No) 
• Time since most recent crisis (months) = (Date of Study Day 1– Date of crisis)/ (365.25/12) 
Note: If the Date of Crisis day and month are missing impute July 2nd, if only the day is missing 
impute the 15th. If the imputed Date of Crisis date is later than the date of Study Day 1, impute 
the date of Study Day 1. 
• Crisis History (Number of crises: 1, 2, 3, more than 3) 
• Reason for switching to study medication (Logistical challenges including travel and time 
spent at a hospital, Challenges with venous access, Lengthy intravenous infusion, Other) 
gMG disease history characteristics will be listed overall. 
6.1.4 
Prior/concomitant/follow-up medications 
6.1.4.1 
Prior/concomitant medications classification 
Medications will be classified as follow based on imputed start and stop dates & times as 
outlined in Section 5.1.1.10.  
• Past medications will include any medications that started and stopped before the first 
administration of IMP.  
• Prior medications will include any medications that started before the first administration of 
IMP. 
• Baseline medications will include any medications that started prior to dosing and continued 
after (classified as prior and concomitant medications). 
• Concomitant medications will include any medications that have been taken at least once 
after the first administration of IMP.  
• Concomitant Only medications will include any medication that started after the first 
administration of IMP. 
Table 6.1: 
Prior and Concomitant Medications 
Medication Started 
Medication finished 
Classification 
Before 1st Dose IMP 
Before 1st Dose IMP 
Past 
Before 1st Dose IMP 
Any time 
Prior 
Before 1st Dose IMP 
After 1st Dose IMP 
Baseline (= prior and concomitant) 
Any time 
After 1st Dose IMP 
Concomitant 
After 1st Dose IMP 
After 1st Dose IMP 
Concomitant Only 
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Where a medication start date is partially or fully missing, and it is unclear as to whether the 
medication is prior or taken at baseline, it will be assumed that it is taken at Baseline. 
6.1.4.2 
Prior and concomitant medications (non-MG therapy) 
A non-MG related medication is defined by the “indication” value on the Prior and Concomitant 
Medication eCRF form not equal to “Therapy for MG”. 
Past, Prior, Baseline, Concomitant or Concomitant Only medications will be summarized on the 
SS. Medications will be presented in alphabetical order by Anatomical Main Group (ATC Level 
1), then by Pharmacological Subgroup (ATC level 3) and finally by decreasing frequency of PT. 
In the case of ties, sort these alphabetically. Summaries will include the overall number and 
percentage of participants receiving at least one treatment of a PT. 
Medications classified as past, prior, baseline, concomitant or concomitant only will be listed 
using the SS. A by-participant listing of concomitant procedures will also be listed using the SS. 
Originally reported dates will be used for listings.  
A by participant listing of Neisseria Meningitidis Vaccination and Prophylaxis will be provided 
in the SS. 
6.1.4.3 
MG Specific Prior and Concomitant Medications 
MG specific medication will be presented separately from the other prior and concomitant 
medications (for both tables and listings). A MG specific medication is defined by the 
“indication” value “Myasthenia Gravis” on the Prior and Concomitant Medication eCRF form. 
MG specific Past, Prior, Baseline, Concomitant and Concomitant only medications will be 
summarized on the SS as defined in Section 6.1.4.2.  
Additionally, the number and percentage of participants who are taking one or more of the sets 
of MG specific medications presented in Table 6.2 (i.e., Groups A-H) will be summarized using 
the same 2 sets of tables: MG specific prior medications and MG specific medications taken at 
baseline.  
Table 6.2: 
Medication class 
Group 
Medication 
Preferred Term on 
Prior/Concomitant eCRF form 
Reported Term on gMG 
Treatment History Form 
A 
Prednisone for gMG 
PREDNISONE 
PREDNISONE 
Other corticosteroids 
for gMG 
DEXAMETHASONE 
METHYLPREDNISONE 
METHYLPREDNISONE 
SODIUM SUCCINATE 
PREDNISOLONE 
METHYLPREDNISOLONE 
HYDROCORTISONE 
TBD** 
OTHER CORTICOSTEROIDS 
PREDNISOLONE 
METHYLPREDNISOLONE 
B 
Azathioprine 
AZATHIOPRINE 
AZATHIOPRINE 
Mycophenolate 
MYCOPHENOLATE MOFETIL 
MYCOPHENOLATE MOFETIL 
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Table 6.2: 
Medication class 
Group 
Medication 
Preferred Term on 
Prior/Concomitant eCRF form 
Reported Term on gMG 
Treatment History Form 
MYCOPHENOLATE ACID 
C 
IVIG 
IMMUNOGLOBULINS 
INTRAVENOUS 
IMMUNOGLOBULIN 
SCIG 
IMMUNOGLOBULINS 
SUBCUTANEOUS 
IMMUNOGLOBULIN 
D 
PLEX* or 
Plasmapheresis 
PLASMA EXCHANGE  
PLASMAPHERESIS 
PLASMA EXCHANGE 
PLASMAPHERESIS 
E 
Cyclosporine 
CICLOSPORIN 
CYCLOSPORINE  
Cyclophosphamide 
CYCLOPHOSPHAMIDE 
CYCLOPHOSPHAMIDE 
Methotrexate 
METHOTREXATE 
METHOTREXATE 
Tacrolimus 
TACROLIMUS 
TACROLIMUS 
Rituximab 
RITUXIMAB 
RITUXIMAB 
 
TBD** 
 
F 
Cholinesterase 
inhibitors 
GALANTAMINE 
GALANTAMINE 
PYRIDOSTIGMINE 
PYRIDOSTIGMINE BROMIDE 
PYRIDOSTIGMINE 
  
AMBENONIUM 
AMBENONIUM CHLORIDE 
AMBENOMIUM CHLORURE 
MYTELASE 
NEOSTIGMINE 
NEOSTIGMINE 
METHYLSULFATE 
NEOSTIGMINE BROMIDE 
DISTIGMINE 
DISTIGMINE BROMIDE 
G 
C5 inhibitors 
ECULIZUMAB 
ECULIZUMAB 
RAVULIZUMAB 
RAVULIZUMAB 
H 
FcRn 
EFGARTIGIMOD 
ROZANOLIXIZUMAB 
EFGARTIGIMOD 
ROZANOLIXIZUMAB 
eCRF=electronic Case Report Form; gMG=generalized myasthenia gravis; IVIG=intravenous immunoglobulin; 
NOS=not otherwise specified; PLEX=plasma exchange; SCIG=subcutaneous immunoglobulin 
*plasma exchange will be on the Procedures eCRF (if concomitant procedure). 
**TBD: To be defined: a complete list of corresponding medications and preferred terms will be provided by UCB 
prior to DBL 
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6.1.5 
Data derivation rules 
6.1.5.1 
MG Activities of Daily Living score (MG-ADL score) 
The MG-ADL is a brief 8-item survey designed to evaluate MG symptom severity. Higher 
scores are associated with more severe symptoms of MG. A 2-point change in MG-ADL Score is 
considered clinically meaningful (Wolfe, Herbelin, Nations, Bryan, & Barohn, 1999); (Muppidi, 
Wolfe, Conaway, & Burns, 2011). 
Table 6.3 presents the 8 items with corresponding response scale, each scored on a 0 to 3-point 
scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). 
 
 
If a participant is missing a response for one of the 8 individual MG-ADL items, the participant’s 
corresponding item score from the previous MG-ADL assessment will be imputed for the 
missing item score (and the total score calculated using this imputed value and the non-missing 
item scores). If the item response is also missing from the previously scheduled MG-ADL, the 
MG-ADL total score will be set to missing for that visit. If the participant is missing responses to 
more than one of the 8 items, the MG-ADL total score will be set to missing for that visit. 
Table 6.3: 
MG-ADL Score 
6.1.5.2 
Quantitative Myasthenia Gravis (QMG) Score 
The QMG is a standardized and validated quantitative strength scoring system that was 
developed specifically for MG. Higher scores are representative of more severe impairment. A 
change in the QMG Score of 3 points or more may be considered clinically meaningful, in a 
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typical clinical trial population of MG patients (Barohn, et al., 1998); (Katzberg, Barnett, 
Merkies, & Bril, 2014). 
Table 6.4 presents the scoring scale for the 13 individual assessments, each scored on a 0 to 3-
point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). 
 
 
If a participant is missing a response for one of the 13 individual QMG items, the participant's 
corresponding item score from the previous QMG assessment will be imputed for the missing 
item score (and the total score calculated using this imputed value and the non-missing item 
scores). If the item response is also missing from the previously scheduled QMG, the QMG total 
score will be set to missing for that visit. If the participant is missing responses to more than one 
of the 13 items, the QMG total score will be set to missing for that visit. 
Table 6.4: 
QMG Score 
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Table 6.4: 
QMG Score 
F=female; M=male. 
The functional sub-scores for a participant are defined as the total score of the corresponding 
items (or the value of the item if it is a single score): 
If an item response has a missing value, the same method as for the QMG total score for 
imputing missing values will be used.  
6.1.5.3 
Myasthenia Gravis Quality of Life (MG-QoL 15r) 
The MG-QOL15r is a 15-item survey that was designed to assess quality of life in patients with 
MG. Higher scores indicate more severe impact of the disease on aspects of the patient’s life 
(Burns, et al., 2010), (Burns, et al., 2016). The following are the 15 questions and the 
corresponding response scales, each scored on a 0–2-point scale (0=Not much at all, 
1=Somewhat, 2=Very Much).  
1. I’m frustrated by my myasthenia gravis.  
2. I have trouble using my eyes because of my MG (e.g., double vision).  
3. I have trouble eating because of my myasthenia gravis.  
4. I have limited my social activity because of my myasthenia gravis.  
5. My myasthenia gravis limits my ability to enjoy hobbies and fun activities.  
6. I have trouble meeting the needs of my family because of my myasthenia gravis.  
7. I have to make plans around my myasthenia gravis.  
8. I am bothered by limitations in performing my work (include work at home) because of my 
myasthenia gravis 
9. I have difficulty speaking due to my myasthenia gravis.  
10. I have lost some personal independence because of my myasthenia gravis (e.g., driving, 
shopping, running errands)  
11. I am depressed about my myasthenia gravis  
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12. I have trouble walking due to my myasthenia gravis  
13. I have trouble getting around public places because of my myasthenia gravis.  
14. I feel overwhelmed by my myasthenia gravis.  
15. I have trouble performing my personal grooming needs due to my myasthenia gravis.  
The MG-QOL15r total score is the sum of the 15 individual item scores with a range of 0 to 30. 
If a participant is missing a response for one of the 15 individual MG-QOL15r items, the 
participant's corresponding item score from the previous MG-QOL15r assessment will be 
imputed for the missing item score (and the total score calculated using this imputed value and 
the non-missing item scores). If the item response is also missing from the previously scheduled 
MG-QOL15r, the MG-QOL15r total score will be set to missing for that visit. If the participant is 
missing responses to more than one of the 15 items, the MG-QOL15r total score will be set to 
missing for that visit. 
6.1.5.4 
Minimal Symptom Expression (MSE) 
MSE is designed to assess how many participants become free or virtually free of MG symptoms 
as measured by achieving an MG-ADL total score of 0 or 1 on therapy (Vissing, et al., 2020). 
6.1.5.5 
MGFA Post-Intervention Status (MGFA-PIS) 
The MGFA-PIS is a physician-determined assessment of clinical symptoms of MG after 
initiation of MG specific therapy.  
Pharmacologic Remission (PR) is defined as follows: The participant has no symptoms or signs 
of MG since baseline and continues to take therapy for MG. Participants taking cholinesterase 
inhibitors are excluded from this category because their use suggests the presence of weakness.  
Minimal manifestation is defined as follows: “The patient has no symptoms of functional 
limitations from MG but has some weakness on examination of some muscles. This class 
recognizes that some patients who otherwise meet the definition of Complete Stable Remission 
or PR do have weakness that is only detectable by careful examination.” For the purpose of the 
current study, minimal manifestation will be determined at each timepoint after treatment 
initiation (rather than after 1 year).  
Change in status since baseline (improved, unchanged, worse, exacerbation, or died of MG) will 
also be determined. 
6.1.5.6 
TSQM-9 questionnaire 
The TSQM-9 is a self-administered PRO with Likert type response options that assesses 
satisfaction with medication use over 3 domains: Effectiveness (items 1 through 3), Convenience 
(items 4 through 6), and Global Satisfaction (items 7 through 9). Each domain score ranges from 
0 to 100, with higher scores indicating increased satisfaction. The instrument is not disease 
specific. The TSQM 9 and previous versions have undergone qualitative and psychometric 
testing and were found to be valid and reliable. 
• The Global Satisfaction subscore is based on Item 7, Item 8 and Item 9 and is calculated as 
follow: 
[(Item 7 + Item 8 + Item 9 – 3)/14]*100 
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If either Item 7 or Item 8 is missing: [(sum of the 2 completed items – 2)/10]*100 
If Item 9 is missing: [(Item 7 + Item 8 – 2)/8]*100 
• The Effectiveness subscore is based on Item 1, Item 2 and Item 3 and is calculated as follow: 
[(Item 1 + Item 2 + Item 3 – 3)/18]*100 
If one Item is missing: [(sum of the 2 completed items – 2)/12]*100 
• The Convenience subscore is based on Item 4, Item 5 and Item 6 and is calculated as follow: 
[(Item 4 + Item 5 + Item 6 – 3)/18]*100 
If one Item is missing: [(sum of the 2 completed items – 2)/12]*100 
6.1.6 
AEs of Interest 
Table 6‒5: 
AEs of Interest selection criteria 
No Event (also included in Title 
of TFL output) 
Selection criteria 
1 
Hypersensitivity reactions  
SMQ=’Hypersensitivity’ (narrow scope) 
2 
Anaphylactic reactions 
SMQ= ‘Anaphylactic reaction’ and  
TEAEs meeting at least one of the following criteria 
where the different terms (within each sub-category) 
occur on the same date or on 2 consecutive days, under 
the condition that the zilucoplan treatment is still 
ongoing at the first of these 2 days. 
1. 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. 
2. 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 or on 2 
consecutive days, 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 or on 2 consecutive days, then both events 
will be flagged as anaphylactic reactions. 
3 
Drug related hepatic disorders  TEAEs in:  
SMQ narrow scope=’Drug related hepatic disorders - 
comprehensive search’ but excluding these 2 sub-
SMQs: “Liver neoplasms, benign (incl cysts and polyps) 
(SMQ)” and “Liver neoplasms, malignant and 
unspecified (SMQ)”.  
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4 
Malignancies or unspecified 
tumours 
TEAEs in:  
SMQ= “Malignant or unspecified tumours (SMQ)” or 
“Malignant tumours (SMQ)” 
Note: the events included in the “Malignant tumours” 
table will be a subset of the events included in the 
“Malignant or unspecified tumours” table. While the 
“Malignant tumours (SMQ)” is most relevant, 
“Malignant or unspecified tumours (SMQ)” must be 
reviewed for potential malignancies.Table  
5 
Injection site reactions 
TEAE with HLT = ’Injection site reactions’ or HLT = 
Administration site reactions NEC’ 
 
Table 6‒6: 
Anaphylactic Reactions Categories 
Category 
Preferred Term 
A 
ANAPHYLACTIC REACTION 
ANAPHYLACTIC SHOCK 
ANAPHYLACTIC TRANSFUSION REACTION 
ANAPHYLACTOID REACTION 
ANAPHYLACTOID SHOCK 
CIRCULATORY COLLAPSE 
DIALYSIS MEMBRANE REACTION 
KOUNIS SYNDROME 
PROCEDURALSHOCK 
SHOCK 
SHOCK SYMPTOM 
TYPE 1 HYPERSENSITIVITY 
B 
ACUTE RESPIRATORY FAILURE 
ASTHMA 
BRONCHIAL OEDEMA 
BRONCHOSPASM 
CARDIO-RESPIRATORY DISTRESS 
CHEST DISCOMFORT 
CHOKING 
CHOKING SENSATION 
CIRCUMORAL OEDEMA 
COUGH  
COUGH VARIANT ASTHMA 
CYANOSIS 
DYSPNOEA 
ENHANCED RESPIRATORY DISEASE 
HYPERVENTILATION 
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Table 6‒6: 
Anaphylactic Reactions Categories 
Category 
Preferred Term 
IRREGULAR BREATHING 
LARYNGEAL DYSPNOEA 
LARYNGEAL OEDEMA 
LARYNGOSPASM 
LARYNGOTRACHEAL OEDEMA 
MOUTH SWELLING 
NASAL OBSTRUCTION 
OEDEMA MOUTH 
OROPHARYNGEAL OEDEMA 
OROPHARYNGEAL SPASM 
OROPHARYNGEAL SWELLING 
PHARYNGEAL SPASM 
PHARYNGEAL SWELLING 
RESPIRATORY ARREST 
RESPIRATORY DISTRESS 
RESPIRATORY FAILURE 
REVERSIBLE AIRWAYS OBSTRUCTION 
SENSATION OF FOREIGN BODY 
SNEEZING 
STRIDOR 
SWOLLEN TONGUE 
TACHYPNOEA 
THROAT TIGHTNESS 
TONGUE OEDEMA 
TRACHEAL OBSTRUCTION 
TRACHEAL OEDEMA 
UPPER AIRWAY OBSTRUCTION 
WHEEZING 
C 
ALLERGIC OEDEMA 
ANGIOEDEMA 
CIRCUMORAL SWELLING 
ERYTHEMA 
EYE OEDEMA 
EYE PRURITUS 
EYE SWELLING 
EYELID OEDEMA 
FACE OEDEMA 
FLUSHING 
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Table 6‒6: 
Anaphylactic Reactions Categories 
Category 
Preferred Term 
INJECTION SITE URTICARIA 
LIP OEDEMA 
LIP SWELLING 
NODULAR RASH 
OCULAR HYPERAEMIA 
OEDEMA 
OEDEMA BLISTER 
PERIORBITAL OEDEMA 
PERIORBITAL SWELLING 
PRURITUS 
PRURITUS ALLERGIC 
RASH 
RASH ERYTHEMATOUS 
RASH PRURITIC 
SKIN SWELLING 
SWELLING 
SWELLING FACE 
SWELLING OF EYELID 
URTICARIA 
URTICARIA PAPULAR 
D 
BLOOD PRESSURE DECREASED 
BLOOD PRESSURE DIASTOLIC DECREASED 
BLOOD PRESSURE SYSTOLIC DECREASED 
CARDIAC ARREST 
CARDIO-RESPIRATORY ARREST 
CARDIOVASCULAR INSUFFICIENCY 
DIASTOLIC HYPOTENSION 
HYPOTENSION 
HYPOTENSIVE CRISIS 
POST PROCEDURAL HYPOTENSION  
 
6.1.7 
Potentially Clinically Significant Criteria for Safety Endpoints 
No additional information. 
 
6.1.8 
Extent of Exposure 
The time to study withdrawal is defined as Date of study withdrawal – date of first IMP + 1. 
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The compliance between 2 clinic visits will be calculated as: (number of syringes dispensed at 
the previous clinic visit – number of unused syringes returned in clinic – total number of 
malfunctioned syringes)/(Date the syringes are returned in clinic – Date the syringes are 
dispensed in clinic)*100.  
The overall compliance in the Main Treatment Period will be calculated as: (total number of 
syringes dispensed – total number of unused syringes – total number of malfunctioned syringes) / 
(Date the last syringes are returned in clinic in the Main Treatment Period – Date the first 
syringes are dispensed in clinic)*100. 
For participants entering in the Extension Treatment Period, the overall compliance in the 
Overall Treatment Period will be calculated as: (total number of syringes dispensed – total 
number of unused syringes – total number of malfunctioned syringes+1)/(Date of last drug 
administration – Date the first syringes are dispensed in clinic in the Main Treatment 
Period+1)*100. 
If the participant was (early) withdrawn, then the date to be considered in the calculation of 
compliance as the end of exposure period will be the date of last administration of Zilucoplan 
and not the date the participant returned the syringes in clinic. Then, the compliance will be 
calculated as follows: (number of syringes dispensed at the previous clinic visit – number of 
unused syringes returned in clinic – total number of malfunctioned syringes+1)/(Date of last drug 
administration – Date the syringes are dispensed in clinic + 1)*100.  
Of note, the number of syringes dispensed at each visit will be derived based on the number of 
kits dispensed at that visit, assuming that each kit contains 7 single dose syringes to be used for 
the daily dosing. 
6.1.9 
COVID-19 terms 
Table 6.7: 
Preferred Terms to define COVID-19 infection 
Name 
Scope 
Asymptomatic COVID-19 
Narrow 
COVID-19 
Narrow 
COVID-19 pneumonia 
Narrow 
COVID-19 treatment 
Narrow 
Post-acute COVID-19 syndrome 
Narrow 
SARS-CoV-2 antibody test positive 
Narrow 
SARS-CoV-2 RNA increased 
Narrow 
SARS-CoV-2 sepsis 
Narrow 
SARS-CoV-2 test false negative 
Narrow 
SARS-CoV-2 test positive 
Narrow 
SARS-CoV-2 viraemia 
Narrow 
Suspected COVID-19 
Narrow 
 
 
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6.2 
Appendix 2: Abnormality criteria for Laboratory, Vital Sign and 
Electrocardiogram Parameters 
6.2.1 
Laboratory Assessments Marked Abnormality Criteria 
The following criteria will be applied in the determination of marked abnormalities for 
laboratory parameters. They are based on Version 5 of the Common Terminology Criteria for 
Adverse Events (CTCAE) grade 3 or higher criteria unless otherwise noted. If both high and low 
criteria are shown for a parameter, the criteria should be summarized separately in tabular or 
graphical summaries. 
Table 6‒8: 
Laboratory Marked Abnormalities  
Parameter 
Unit 
(conventional) 
Unit  
(Standard) 
Marked Abnormality Criteria 
Hematology 
 
 
 
Hemoglobin 
g/dL 
g/L 
<8.0 g/dL; <80 g/L 
WBC (Leukocytes)  
109/L 
109/L  
Low: <2.0 x 109/L 
High: >100 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 
Eosinophils 
109/L 
109/L 
≥1.5 x 109/L  
Biochemistry 
 
 
 
AST 
U/L 
U/L 
>5.0 x ULN if Baseline value is 
normal; >5.0 x Baseline value if 
Baseline is abnormal 
ALT 
U/L 
U/L 
>5.0 x ULN if Baseline value is 
normal; >5.0 x Baseline value if 
Baseline is abnormal 
ALP 
U/L 
U/L 
>5.0 x ULN if Baseline value is 
normal; >5.0 x Baseline value if 
Baseline is abnormal 
Bilirubin (total) 
 
mg/dL 
umol/L 
>3.0 x ULN if Baseline value is 
normal 
> 3.0 x Baseline value if Baseline is 
abnormal 
Creatinine 
mg/dL 
umol/L 
>3.0 x ULN 
Estimate glomerular 
filtrate rate (eGFR)a 
mL/min/1.73 m2 
mL/min/1.73 m2 
<29 mL/min/1.73m2 
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Parameter 
Unit 
(conventional) 
Unit  
(Standard) 
Marked Abnormality Criteria 
Glucoseb 
mg/dL 
mmol/L 
Low: <40 mg/dL; < 2.2 mmol/L 
High: >250 mg/dL; >13.9 mmol/L 
Potassium 
mEq/L 
mmol/L 
Low: <3.0 mmol/L 
High: >6.0 mmol/L 
Sodium 
mEq/L 
mmol/L 
Low: <125 mmol/L 
High: >155 mmol/L 
Amylase 
U/L 
U/L 
>2.0 x ULN  
Lipase 
U/L 
U/L 
>2.0 x ULN 
ALT= alanine aminotransferase; AST = aspartate aminotransferase; CRP = C-reactive protein; dL = deciliter;  
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. 
a eGFR is calculated using the Chronic Kidney Disease Epidemiology Collaboration or CKD-EPI formula 
(https://qxmd.com/calculate/calculator_251/egfr-using-ckd-epi) which is eGFR = 141 * min(Scr/κ,1)α * 
max(Scr/κ, 1)-1.209 * 0.993Age * 1.018 [if female] * 1.159 [if black]; where Scr is serum creatinine (mg/dL), κ is 0.7 
for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 
1, and max indicates the maximum of Scr/κ or 1. For derivation from values in standard units (umol/L) the κ 
values are 61.9 for females and 79.6 for males. Subjects with missing race should be considered as non-black for 
eGFR calculation.  
b Glucose high criterion defined by Grade 3 and higher events according to CTCAE, Version 4.03, June 14, 2010 
6.2.2 
Marked Abnormalities Vital Signs 
Abnormality criteria to be applied in the assessment of vital signs parameter values are given 
below: 
Table 6‒9: 
Marked Abnormalities Vital Signs 
Parameter 
Abnormality Criteria 
Pulse rate (beats/min) 
≤50 and a decrease from Baseline≥15 
≥120 and an increase from Baseline≥15 
Systolic Blood Pressure (mmHg) 
≤90 and a decrease from Baseline≥20 
≥160 and an increase from Baseline≥20 
Diastolic Blood Pressure (mmHg) 
≤50 and a decrease from Baseline≥15 
≥105 and an increase from Baseline≥15 
Temperature 
>1010F (38.3 0C) 
Body Weight 
≥ 10% decrease from Baseline 
≥ 10% increase from Baseline 
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6.2.3 
Marked Abnormalities Electrocardiogram (ECG) 
Abnormality criteria to be applied in the assessment of ECG parameter values are given below: 
Table 6‒10: Marked Abnormalities (ECG) 
Parameter 
Treatment Emergent Markedly Abnormal 
Criteria 
QT interval (ms) 
≥500ms 
≥60ms increase from Baseline 
QTcF (ms) 
≥500ms 
≥60ms increase from Baseline 
PR interval (ms) 
Treatment-emergent value >200ms 
QRS interval (ms) 
Treatment-emergent value >100ms 
Heart Rate (bpm) 
<50bpm 
>120bpm 
Abbreviations: bpm = beats per minute; ms = milliseconds; QTc(F) = Fridericia corrected QT interval;  
Note: Treatment-emergent is defined as meeting the MA criteria at any post-Baseline visit after the first dose of IMP 
and not meeting the MA criteria at Baseline. 
 
6.3 
Appendix 3: Changes to Protocol-Planned Analyses 
The description of compliance has been added. 
More precision on the model used for the main secondary endpoint strategy (MMRM followed 
by a One-Sample t-test on the LS Means) were given. 
 
 
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7 
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