An Open-Label, Single Center, Randomized, 2-Way Crossover, Single-Dose, Bioequivalence Study of Zilucoplan Injected Subcutaneously Either by a Prefilled Syringe or an Auto-Injector in Healthy Adult Participants
Phase: PHASE1
Conditions: Healthy Volunteers
Sponsor: UCB Biopharma SRL

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 1 of 68 
AN OPEN-LABEL, SINGLE CENTER, RANDOMIZED, 2-WAY 
CROSSOVER, SINGLE-DOSE, BIOEQUIVALENCE STUDY OF 
ZILUCOPLAN INJECTED SUBCUTANEOUSLY EITHER BY A 
PREFILLED SYRINGE OR AN AUTO-INJECTOR IN HEALTHY 
ADULT PARTICIPANTS 
PROTOCOL DV0012 
PHASE 1 
 
SHORT TITLE: 
An open-label, single center, randomized, 2-way crossover, single dose, bioequivalence study of 
zilucoplan injected subcutaneously in healthy adult participants 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying number(s): 
EudraCT Number: 
Not applicable 
EU CT Number: 
2023-508388-64-00 
EUDAMED Number: 
Not applicable 
IND Number: 
Not applicable 
IDE Number: 
Not applicable 
NCT Number: 
Currently not available 
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. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 2 of 68 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document History 
Document 
Date 
Type of amendment 
Original Protocol 
11 Dec 2023 
Not applicable 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 3 of 68 
SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h) 
Fax 
Europe and Rest of the World: +32 2 386 24 21 
US and Canada: +1 800 880 6949  or +1 866 890 3175 
Email 
Global: DS_ICT@ucb.com (for interventional clinical studies) 
 
SAFETY REPORTING OF ADVERSE EVENTS (SERIOUS AND 
NONSERIOUS) AND DEVICE DEFICIENCIES 
Safety reporting of adverse events (24h) 
Email 
Global: DS_ICT@ucb.com 
Fax 
+32 2 386 24 21 
 
SAFETY REPORTING OF ADVERSE DEVICE EFFECTS (SERIOUS AND 
NONSERIOUS) AND DEVICE DEFICIENCIES 
Reporting of adverse device effects (serious and nonserious) and device 
deficiencies for UCB devices used in the study (24h) 
eCRF 
The mechanism for reporting an adverse device effects and device 
deficiencies to UCB (or its representative) will be the electronic data 
collection tool. 
Email 
Global: qactscomplaints@ucb.com 
 
Note: In case of a device related event or a device deficiency for 
UCB devices or device constituents, these should be captured in the 
electronic data collection (EDC) tool and an investigational 
medicinal product (IMP) complaint form should be filled. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 4 of 68 
TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ................................................................................................. 8 
1.1 
Synopsis ......................................................................................................................... 8 
1.2 
Schema ......................................................................................................................... 11 
1.3 
Schedule of Activities .................................................................................................. 12 
2 
INTRODUCTION ........................................................................................................... 15 
2.1 
Study rationale ............................................................................................................. 15 
2.2 
Background .................................................................................................................. 15 
2.3 
Benefit/risk assessment ................................................................................................ 16 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 17 
4 
STUDY DESIGN ............................................................................................................. 17 
4.1 
Overall design .............................................................................................................. 17 
4.2 
Scientific rationale for study design ............................................................................ 18 
4.2.1 
Patient input into design ...................................................................................... 18 
4.3 
Justification for dose .................................................................................................... 18 
4.4 
End of study definition................................................................................................. 19 
5 
STUDY POPULATION .................................................................................................. 19 
5.1 
Inclusion criteria .......................................................................................................... 19 
5.2 
Exclusion criteria ......................................................................................................... 20 
5.3 
Lifestyle restrictions..................................................................................................... 22 
5.4 
Screen failures .............................................................................................................. 22 
6 
STUDY TREATMENTS/INVESTIGATIONAL DEVICE ............................................ 22 
6.1 
Treatments administered .............................................................................................. 22 
6.1.1 
Devices ................................................................................................................ 24 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 24 
6.2.1 
Drug accountability/Device accountability ......................................................... 24 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 25 
6.4 
Treatment compliance .................................................................................................. 25 
6.5 
Concomitant medication(s)/treatment(s) ..................................................................... 25 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 25 
6.5.2 
Prohibited concomitant treatments (medications and therapies) ......................... 26 
6.5.3 
Rescue medication ............................................................................................... 26 
6.6 
Dose modification ........................................................................................................ 26 
6.7 
Criteria for study hold or dosing stoppage ................................................................... 26 
6.8 
Treatment after the end of the study ............................................................................ 26 
7 
DISCONTINUATION OF IMP AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 27 
7.1 
Discontinuation of IMP................................................................................................ 27 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 5 of 68 
7.2 
Participant discontinuation/withdrawal from the study ............................................... 27 
7.3 
Lost to follow-up.......................................................................................................... 27 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 28 
8.1 
Pharmacokinetics ......................................................................................................... 28 
8.2 
Safety assessments ....................................................................................................... 29 
8.2.1 
Adverse events and serious adverse events ......................................................... 29 
8.2.2 
Time period and frequency for collecting AE and SAE information .................. 29 
8.2.3 
Method of detecting AEs and SAEs .................................................................... 30 
8.2.4 
Follow-up of AEs and SAEs ................................................................................ 30 
8.2.5 
Regulatory reporting requirements for SAEs ...................................................... 30 
8.2.6 
Pregnancy ............................................................................................................ 31 
8.2.7 
Adverse events of special monitoring .................................................................. 31 
8.2.8 
Device – adverse events (ADEs, UADEs, SAEs, SADEs, and USADEs) and 
device deficiencies ............................................................................................... 31 
8.2.8.1 
Time period for detecting ADEs and device deficiencies ......................... 31 
8.2.8.2 
Follow-up of ADEs and device deficiencies ............................................. 32 
8.2.8.3 
Prompt reporting of ADEs and device deficiencies to Sponsor ................ 32 
8.2.8.4 
Regulatory reporting requirements for ADEs and device deficiencies ..... 32 
8.2.9 
Clinical safety laboratory assessments ................................................................ 32 
8.2.10 
Vital signs ............................................................................................................ 33 
8.2.11 
Electrocardiograms .............................................................................................. 33 
8.2.12 
Physical examination ........................................................................................... 33 
8.3 
Safety signal detection ................................................................................................. 34 
8.4 
Treatment of overdose ................................................................................................. 34 
8.5 
Biomarkers ................................................................................................................... 34 
8.6 
Immunogenicity assessments ....................................................................................... 34 
8.7 
Medical resource utilization and health economics ..................................................... 34 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 34 
9.1 
Definition of analysis sets ............................................................................................ 34 
9.2 
General statistical considerations ................................................................................. 35 
9.3 
Planned PK analyses .................................................................................................... 35 
9.3.1 
Analysis of the primary endpoint ........................................................................ 35 
9.3.2 
Exploratory endpoint analyses ............................................................................. 36 
9.4 
Planned safety and other analyses................................................................................ 36 
9.4.1 
Safety analyses ..................................................................................................... 36 
9.4.1.1 
Secondary endpoint analyses ..................................................................... 36 
9.4.1.2 
Exploratory endpoint analyses .................................................................. 36 
9.4.2 
Other analyses ...................................................................................................... 37 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 6 of 68 
9.4.2.1 
Exploratory endpoint analyses .................................................................. 37 
9.5 
Handling of protocol deviations................................................................................... 37 
9.6 
Handling of dropouts or missing data .......................................................................... 37 
9.7 
Planned interim analysis and data monitoring ............................................................. 37 
9.8 
Determination of sample size ....................................................................................... 37 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 39 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ......................... 39 
10.1.1 
Regulatory and ethical considerations ................................................................. 39 
10.1.2 
Financial disclosure ............................................................................................. 39 
10.1.3 
Informed consent process .................................................................................... 40 
10.1.4 
Data protection ..................................................................................................... 40 
10.1.5 
Committees structure ........................................................................................... 41 
10.1.6 
Dissemination of clinical study data .................................................................... 41 
10.1.7 
Data quality assurance ......................................................................................... 41 
10.1.7.1 
Case report form completion ..................................................................... 42 
10.1.7.2 
Apps ........................................................................................................... 42 
10.1.8 
Source documents ................................................................................................ 42 
10.1.9 
Study and site start and closure ........................................................................... 42 
10.1.10 
Publication policy ................................................................................................ 43 
10.2 
Appendix 2: Clinical laboratory tests .......................................................................... 44 
10.3 
Appendix 3: Adverse events – Definitions and procedures for recording, evaluating, 
follow-up, and reporting .............................................................................................. 46 
10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ......... 51 
10.5 
Appendix 5: Genetics ................................................................................................... 55 
10.6 
Appendix 6: Liver safety – suggested actions and follow-up assessments ................. 56 
10.7 
Appendix 7: Device adverse events (AEs), adverse device effects (ADEs), serious 
adverse events (SAEs), and device deficiencies: Definition and procedures for 
recording, evaluating, follow up, and reporting ........................................................... 57 
10.7.1 
Definitions of AE and ADE ................................................................................. 57 
10.7.2 
Definitions of SAE, SADE, and USADE ............................................................ 58 
10.7.3 
Definition of device deficiency ........................................................................... 58 
10.7.4 
Recording and follow up of AE and/or SAE and device deficiencies ................. 59 
10.7.5 
Reporting of SAEs ............................................................................................... 61 
10.7.6 
Reporting of SADEs ............................................................................................ 61 
10.8 
Appendix 8: Rapid alert procedures ............................................................................ 62 
10.9 
Appendix 9: Country-specific requirements ................................................................ 63 
10.10 Appendix 10: Abbreviations and trademarks .............................................................. 64 
10.11 Appendix 11: Protocol amendment history ................................................................. 66 
11 REFERENCES ................................................................................................................ 67 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 7 of 68 
SPONSOR DECLARATION .................................................................................................. 68 
 
LIST OF TABLES 
Table 1-1: 
Schedule of study assessments......................................................................... 12 
Table 3-1: 
Objectives and endpoints ................................................................................. 17 
Table 4-1: 
Zilucoplan weight-bracketed dosing ................................................................ 19 
Table 6-1: 
Treatment administered ................................................................................... 23 
Table 8-1: 
Time Windows for PK sampling ..................................................................... 29 
 
LIST OF FIGURES 
Figure 1-1: 
Study schematic ............................................................................................... 11 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 8 of 68 
1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title: 
An open-label, single center, randomized, 2-way crossover, single dose, bioequivalence study of 
zilucoplan injected subcutaneously either by a prefilled syringe or an auto-injector in healthy 
adult participants 
Short title: 
An open-label, single center, randomized, 2-way crossover, single dose, bioequivalence study of 
zilucoplan injected subcutaneously in healthy adult participants 
Rationale: 
Myasthenia gravis (MG) is a serious, sometimes life-threatening, debilitating condition 
associated with numerous symptoms, including muscular weakness and fatigue. Some patients 
can manage their symptoms with oral medications, such as oral acetylcholinesterase inhibitors, 
corticosteroids, or nonsteroidal immunosuppressants. In addition, intravenous (IV) 
immunoglobulin G and plasma exchange treatment can 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 complement component 5 (C5) inhibitors (eg, eculizumab or 
ravulizumab) which have proven effective at treating MG symptoms. 
Zilucoplan (RA101495; ZLP) has recently been approved in Japan, the US, and the EU. It 
reduces the administration burden, can be used by patients with difficult venous access, or who 
are in underserved or rural populations where economic access to IV infusions is prohibitive. 
Zilucoplan is currently approved as a pre-filled syringe (PFS) for subcutaneous (sc) injection; 
however, it is expected that there will be a need to have different treatment administration 
options available for the administration of ZLP and that individuals may prefer to have the 
option to administer their ZLP medication using an auto-injector (AI). DV0012 will, therefore, 
assess the bioequivalence of ZLP pharmacokinetics (PK) between a single sc injection of ZLP 
from a ZLP-PFS and ZLP-AI, and evaluate the ZLP PK, safety, and tolerability in healthy study 
participants who receive a single sc injection of ZLP from a ZLP-PFS and ZLP-AI. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 9 of 68 
Objectives and endpoints 
Objectives 
Endpoints 
Primary 
• To establish the bioequivalence of ZLP 
pharmacokinetics (PK) after a single sc 
injection with ZLP safety syringe 
(ZLP- PFS) and ZLP-AI 
• Area under the plasma concentration-time 
curve from time 0 to infinity (AUC) 
• Area under the plasma concentration-time 
curve from time 0 to time t (AUC0-t) 
• Maximum observed plasma concentration 
(Cmax) 
Secondary 
• To evaluate the safety and tolerability of 
ZLP after a single sc injection with 
ZLP-PFS and ZLP-AI 
• Occurrence of treatment-emergent 
adverse events (TEAEs), serious adverse 
events (SAEs), and adverse device effects 
(ADEs, serious and nonserious) from 
Day 1 up to the End of Study (EOS) or 
Early Termination (ET) Visit 
Exploratory 
• To further evaluate the safety and 
tolerability of ZLP after a single sc 
injection with ZLP-PFS and ZLP-AI 
• To further evaluate the PK of ZLP after a 
single sc injection with ZLP-PFS and 
ZLP-AI 
• To evaluate device deficiencies 
• Change from Baseline in clinical 
laboratory tests (hematology, clinical 
chemistry, and urinalysis) 
• Terminal half-life (t½) 
• Apparent plasma clearance (CL/F) 
• Time to maximum observed concentration 
(tmax) 
• Apparent volume of distribution (Vz/F) 
• Device deficiencies as reported via the 
electronic case report form (eCRF) 
Overall design 
DV0012 is a Phase 1, open-label, single-center, randomized, 2-way crossover study in 14 healthy 
study participants designed to establish bioequivalence in ZLP PK between a single sc injection 
of ZLP from a ZLP-PFS (reference) and a ZLP-AI (test), and to investigate the PK, safety, and 
tolerability in healthy study participants who receive a single sc injection of ZLP. 
The crossover design allows each participant to receive a single ZLP injection with each of the 
2 devices (ZLP-PFS and ZLP-AI). Zilucoplan will be administered as a single sc injection in the 
abdomen to evaluate the potential impact of using 2 different devices (ZLP-PFS and ZLP-AI) on 
the PK endpoints. The volume of ZLP will differ from participant to participant depending on 
their body weight on Treatment Period 1 Day -1. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 10 of 68 
Study personnel will administer 1 injection of ZLP to the study participant on Day 1 of each 
Treatment Period following detailed instructions that will have been provided. Injections into the 
abdomen must avoid the 5 cm/2-inch area around the belly button (navel). No injections should 
be administered into an area that is tender, red, bruised, hard, or that has scars or stretch marks. 
Fourteen healthy study participants will be randomized 1:1 to treatment sequence AB or BA, 
where treatment A is ZLP-PFS injection device and treatment B is ZLP-AI injection device (see 
study schematic in Section 1.2). Following completion of the first Treatment Period and a 7-day 
Washout Period, study participants will then complete the second Treatment Period with the 
same dose level as in Treatment Period 1 but using the alternate device. 
Study participants will have End of Study (EOS) procedures performed on the last sampling day 
(Day 35) of Treatment Period 2, in addition to the Day 35 procedures. 
Study participants who are unable to complete the study will return to the study center for the 
Early Termination (ET) Visit as soon as possible after the time of withdrawal and will have all 
Day 35 and EOS procedures performed (ie, Day 35 of the Treatment Period in which they 
withdrew from the study). 
Number of participants 
A sufficient number of study participants will be screened to ensure that 7 study participants are 
randomized to each of the 2 treatment sequences (14 study participants in total), with the 
objective of having at least 12 study participants complete the study. See Section 9.8 for more 
details. Study participants who withdraw or are withdrawn from the study after dosing will not 
be replaced. However, if the number of dropouts exceeds initial expectations, study participants 
who withdraw or are withdrawn might be replaced at the discretion of the Sponsor. 
Treatment groups and duration 
Zilucoplan will be provided as a single-use injection in a needle safety device (ZLP-PFS) or a 
ZLP-AI device using weight-bracketed dosing (ie, participants will be provided ZLP-PFS or 
ZLP-AI containing fixed amounts of ZLP based on their weight, and each fixed amount will 
cover a range of participant weights). 
The total maximum study duration per study participant will be up to 15 weeks, as follows: 
• Screening Period: Up to 35 days (Days -35 to -2). 
• In-Clinic Period (BL): 1 day (Day -1). 
• Treatment Period 1 and Treatment Period 2: 5 weeks each (Days 1-35; approximately 5 times 
the half-life of ZLP). Each Treatment Period includes: 
- a 2-day In-Clinic Period (Days 1 and 2). 
- a 33-day Observation Period. 
− On Days 3, 5, 8, 15, 22, 29, and 35 of the Observation Period, participants will attend the 
study center to allow study assessments to be completed. 
• Washout Period between Treatment Period 1 and Treatment Period 2: 1 week (7 days). 
• The EOS Visit procedures will be performed on Day 35 of Treatment Period 2 (ie, on Study 
Day 77). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 11 of 68 
1.2 
Schema 
Figure 1-1: Study schematic 
 
ZLP-AI=zilucoplan-autoinjector; ZLP-PFS=ZLP prefilled syringe 
 
Treatment Period 1
(Day 1 to Day 35)
Treatment Period 2
(Day 1 to Day 35)
Sequence AB
Sequence BA
Randomization
Screening
Washout Period 
(7 days)
Washout Period
(7 days)
Treatment A (Day 1):
ZLP-PFS injection method 
Treatment B (Day 1):
ZLP-AI injection method
Sequence BA
Sequence AB
Treatment A (Day 1):
ZLP-PFS injection method 
Treatment B (Day 1):
ZLP-AI injection method
(up to 4 weeks)
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 12 of 68 
1.3 
Schedule of Activities 
Table 1-1: 
Schedule of study assessments 
Procedure 
 
Screening 
Period 
In-
Clinic 
Period 
(BL)c 
Treatment Periods 1 and 2d 
EOS/ETe 
In-Clinic 
Periodc 
Observation Periodc 
Daya 
-35 to -2 
-1 
1 
2 
3 
5 
8 
15 
22 
29 
35 
Written informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationf 
X 
X 
 
 
 
 
 
 
 
 
X 
 
Pregnancy testg 
X 
X 
 
 
 
 
 
 
 
 
 
 
Height and weighth 
X 
X 
 
 
 
 
 
 
 
 
 
 
Serum FSH leveli 
X 
 
 
 
 
 
 
 
 
 
 
 
Viral serology (HBsAg, HCV, 
HIV, and syphilis) 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine drug test 
X 
X 
 
 
 
 
 
 
 
 
 
 
Alcohol breath test 
X 
X 
 
 
 
 
 
 
 
 
 
 
COVID-19 precautionsj 
X 
X 
 
 
 
 
 
 
 
 
 
 
Vital signsk 
 
Xb 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory tests 
(hematology, clinical 
chemistry, and urinalysis) 
X 
Xb 
 
 
 
 
 
X 
 
 
 
X 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 13 of 68 
Table 1-1: 
Schedule of study assessments 
Procedure 
 
Screening 
Period 
In-
Clinic 
Period 
(BL)c 
Treatment Periods 1 and 2d 
EOS/ETe 
In-Clinic 
Periodc 
Observation Periodc 
Daya 
-35 to -2 
-1 
1 
2 
3 
5 
8 
15 
22 
29 
35 
Throat swab for N. 
meningitidis 
X 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
Recording of prior and 
concomitant medication and 
procedures 
X 
Xb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Recording of AEs 
X 
Xb 
Xl 
Xl 
X 
X 
X 
X 
X 
X 
X 
X 
N. meningitidis vaccinationm 
X 
SoC 
SoC 
SoC 
SoC 
SoC 
SoC 
SoC 
SoC 
SoC 
SoC 
SoC 
Randomization 
 
Xn 
 
 
 
 
 
 
 
 
 
 
IMP administrationo 
 
 
X 
 
 
 
 
 
 
 
 
 
Blood sampling for PKp 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Recording of device 
deficiencies and product 
quality complaintsq 
 
 
X 
 
 
 
 
 
 
 
 
 
AE=adverse event; BL=Baseline; COVID-19=coronavirus disease 2019; ECG=electrocardiogram; eCRF=electronic case report form; EOS=end of study; 
ET=early termination; FSH=follicle-stimulating hormone; HBsAg=hepatitis B surface antigen; HCV=hepatitis C virus; HIV=human immunodeficiency virus; 
IMP=investigational medicinal product; N. meningitidis=Neisseria meningitidis; PK=pharmacokinetic, SoC=standard of care 
a Day -35 to -2 is relative to Day 1 in Treatment Period 1; all other days are relative to Day 1 within each Treatment Period. 
b Baseline Day -1 procedures are repeated on Day -1 prior to Treatment Period 2, unless otherwise stated. Procedures to be repeated on the second Baseline 
Day -1 include vital signs, laboratory assessments, and recording of concomitant medications and AEs. 
c Days -1, 1, and 2 are part of the In-Clinic Period; on Days 3, 5, 8, 15, 22, 29, and 35 of the Observation Period, participants will attend the study center to allow 
study assessments to be completed. 
d Each participant will attend 2 Treatment Periods. There will 7 days of washout after completion of the first Treatment Period before returning to the study 
center for the second Treatment Period. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 14 of 68 
e Study participants will have EOS procedures performed on the last sampling day (Day 35) of Treatment Period 2, in addition to the Day 35 procedures. 
Participants who prematurely withdraw from the study will return to the study center for the ET Visit as soon as possible after the time of withdrawal and will 
have all Day 35 (ie, Day 35 of the Treatment Period in which they withdrew from the study) and EOS procedures performed. 
f A full physical examination will be performed on all participants at Screening. On all other clinic visit days, the physical examination will be symptom 
directed. 
g For all women of childbearing potential, pregnancy testing will consist of a urine pregnancy test at the Screening and Baseline visits. Pregnancy test results 
must be negative prior to administering IMP. Positive urinary test will be exclusionary. Participant may rescreen at a later time if pregnancy not confirmed 
subsequently with a serum test. 
h Height will be measured only at the Screening Visit. 
i Only for postmenopausal women (for at least 1-year post-menopause before the Screening Visit) not using hormonal contraception or hormone replacement 
therapy. 
j COVID-19 precautions: latest procedure; site should follow local procedures/local policy for the management of COVID-19. 
k Systolic and diastolic blood pressure, pulse rate, and oral body temperature. Blood pressure and pulse measurements should be preceded by at least 5 minutes 
of rest for the participant. 
l If an injection site reaction is observed or reported by the participant, it should be recorded as an AE in the Case Report Form. 
m To reduce the risk of meningococcal infection (N. meningitidis), all study participants must be vaccinated against meningococcal infections (with a 
quadrivalent vaccine and serogroup B vaccine) within 3 years prior to, or at least 2 weeks prior to the start of initiating the IMP. 
n Treatment Period 1 only. 
o Study personnel will administer 1 injection to the study participant into the abdomen on Day 1 of each Treatment Period. The same dose of IMP will be 
administered for both Treatment Periods. 
p The PK sampling timepoints for each treatment period will be on Day 1 at predose and at 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, and 12h and at 24h (Day2), 48h (Day 3), 
96h (Day 5), 168h (Day 8), 336h (Day 15), 504h (Day 22), 672h (Day 29), and 816h (Day 35) postdose. 
q Device deficiencies will be reported via the eCRF. In addition, sites will fill out a product quality complaint form; all product quality complaints will be 
investigated by UCB. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 15 of 68 
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. Some patients can manage their 
symptoms with oral medications, such as oral acetylcholinesterase inhibitors, corticosteroids, or 
nonsteroidal immunosuppressants. In addition, IV immunoglobulin G and plasma exchange 
treatment can 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. 
Zilucoplan (RA101495; ZLP) has recently been approved in Japan, the US, and the EU. It 
reduces the administration burden, can be used by patients with difficult venous access, or who 
are in underserved or rural populations where economic access to IV infusions is prohibitive. 
Zilucoplan is currently approved as a PFS for sc injection; however, it is expected that there will 
be a need to have different treatment administration options available for the administration of 
ZLP and that individuals may prefer to have the option to administer their ZLP medication using 
an AI. DV0012 will, therefore, assess the bioequivalence of ZLP PK between a single sc 
injection of ZLP from a ZLP-PFS and ZLP-AI, and evaluate the ZLP PK, safety, and tolerability 
in healthy study participants who receive a single sc injection of ZLP from a ZLP-PFS and a 
ZLP-AI. 
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 globally is estimated to 
be 12.4 (range 10.6 to 14.5) per 100,000 persons (Salari et al, 2021); hence, MG affects up to 
approximately 760,000 people worldwide. Myasthenia gravis most commonly affects young 
adult women (under 40) and older men (over 60), but it can occur at any age. Epidemiological 
studies reveal an increasing prevalence over the past 50 years, due in part to an increase in the 
frequency of diagnosis in the elderly (Sanders et al, 2016). As the population has aged, the 
average age at onset has increased correspondingly.  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 generalized MG (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). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 16 of 68 
Zilucoplan 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 following activation of 
classical or alternative complement pathways, as well as inhibition of red blood cell lysis in the 
serum/plasma from various species. 
The clinical efficacy of ZLP in gMG has been shown in a Phase 2 study, MG0009 (previously 
RA101495-02.201) (Howard  et al, 2021), and in a Phase 3 study, MG0010 (previously 
RA101495-02.301) (Howard et al, 2023). In addition, ZLP has shown a favorable safety and 
tolerability profile across all completed studies. Further details are provided in the ZLP IB. 
2.3 
Benefit/risk assessment 
This study will not provide a benefit to the study population, ie, healthy study participants. 
The primary risk associated with C5 inhibitors as a class is increased susceptibility to infections 
with encapsulated bacteria, such as Neisseria spp. Specifically, this risk is related to suppression 
of the innate immune response and subsequent infections, particularly meningococcal infections. 
It is well established that inhibition of C5 and the terminal complement pathway increases the 
susceptibility to Neisseria spp. infections. Given the known increased risk of meningococcal 
infection (Neisseria. meningitidis) associated with inhibition or inherited deficiency of C5, 
participants in this study will be required to have documentation of N. meningitidis vaccination 
at least 2 weeks prior to IMP administration, if not vaccinated within 3 years prior to the start of 
treatment. Participants must be vaccinated with a quadrivalent vaccine (where available and in 
accordance with local standard of care) and serogroup B vaccine against meningococcal 
infections (N. meningitidis), and booster vaccinations should be administered in accordance with 
local standard of care. In addition, while on ZLP, study participants must be monitored closely 
for signs and symptoms of N. meningitidis infection, including self-monitoring on detailed 
instructions about signs and symptoms of possible meningococcal infections. To date, no 
meningococcal infections have been identified with ZLP treatment in clinical studies, as the risk 
of Neisseria infection is well-managed by appropriate prophylactic vaccination. 
Considering the potential benefits, risks, and mitigation measures in place, UCB considers the 
overall benefit/risk to be favorable for participants in this study. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of ZLP may be found in the ZLP IB and Zilbrysq summary of product 
characteristics (SmPC). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 17 of 68 
3 
OBJECTIVES AND ENDPOINTS 
Table 3-1: 
Objectives and endpoints 
Objectives 
Endpoints 
Primary 
• To establish the bioequivalence of ZLP 
PK after a single sc injection with ZLP 
safety syringe (ZLP- PFS) and ZLP-AI 
• AUC 
• AUC0-t 
• Cmax 
Secondary 
• To evaluate the safety and tolerability of 
ZLP after a single sc injection with 
ZLP-PFS and ZLP-AI 
• Occurrence of TEAEs, SAEs, and ADEs 
(serious and nonserious) from Day 1 up to 
the EOS or ET visit 
Exploratory 
• To further evaluate the safety and 
tolerability of ZLP after a single sc 
injection with ZLP-PFS and ZLP-AI 
• To further evaluate the PK of ZLP after a 
single sc injection with ZLP-PFS and 
ZLP-AI 
• To evaluate device deficiencies 
• Change from Baseline in clinical 
laboratory tests (hematology, clinical 
chemistry, and urinalysis) 
• t½ 
• CL/F 
• tmax 
• Vz/F 
• Device deficiencies as reported via the 
eCRF 
ADE=adverse device effect; AUC=area under the plasma concentration-time curve from time 0 to infinity; 
AUC0-t=area under the plasma concentration-time curve from time 0 to time t; Cmax= maximum observed plasma 
concentration; eCRF=electronic case report form; EOS= End of Study; ET= early termination; 
PK=pharmacokinetics; PFS=prefilled syringe; SADE=serious adverse device effects; SAE=serious adverse event; 
sc=subcutaneous; t½=terminal half-life; TEAE=treatment-emergent adverse event; tmax=time to maximum 
observed concentration; Vz/F= apparent volume of distribution; ZLP-AI=zilucoplan-autoinjector; 
ZLP-PFS=zilucoplan-prefilled syringe 
4 
STUDY DESIGN 
4.1 
Overall design 
DV0012 is a Phase 1, open-label, single-center, randomized, 2-way crossover study in 14 healthy 
study participants designed to establish bioequivalence in ZLP pharmacokinetics (PK) between a 
single sc injection of ZLP from a prefilled syringe (ZLP-PFS; reference) and an auto-injector 
device (ZLP-AI; test), and to investigate the safety, tolerability, and PK in study participants who 
receive a single sc injection of ZLP. 
The crossover design allows each participant to receive a single ZLP injection with each of the 
2 devices (ZLP-PFS and ZLP-AI). Zilucoplan will be administered as a single sc injection in the 
abdomen to evaluate the potential impact of using 2 different devices (ZLP-PFS and ZLP-AI) on 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 18 of 68 
the PK endpoints. The volume of ZLP will differ from participant to participant depending on 
their body weight on Treatment Period 1 Day -1. 
Study personnel will administer 1 injection of ZLP to the study participant on Day 1 of each 
Treatment Period following detailed instructions that will have been provided. Injections into the 
abdomen must avoid the 5 cm/2-inch area around the belly button (navel). No injections should 
be administered into an area that is tender, red, bruised, hard, or that has scars or stretch marks. 
A sufficient number of study participants will be screened to ensure that 7 study participants are 
randomized to each of the 2 treatment sequences (14 study participants in total), with the 
objective of having at least 12 study participants complete the study. See Section 9.8 for more 
details. 
Fourteen healthy study participants will be randomized 1:1 to treatment sequence AB or BA, 
where treatment A is ZLP-PFS injection device and treatment B is ZLP-AI injection device (see 
study schematic in Section 1.2). Following completion of the first Treatment Period and a 7-day 
Washout Period, study participants will then complete the second Treatment Period with the 
same dose as in Treatment Period 1. 
Study participants will have End of Study (EOS) procedures performed on the last sampling day 
(Day 35) of Treatment Period 2, in addition to the Day 35 procedures. 
Study participants who are unable to complete the study will return to the study center for the 
Early Termination (ET) Visit as soon as possible after the time of withdrawal and will have all 
Day 35 and EOS procedures performed (ie, Day 35 of the Treatment Period in which they 
withdrew from the study). 
4.2 
Scientific rationale for study design 
The current study is considered a ‘single dose’ study with a single dose given twice to each study 
participant, once by each injection device. The participants will receive the same dose during 
both Treatment Periods based on the weight reported at Day -1 of Treatment Period 1. The order 
of injection devices will be defined by the sequence each study participant is randomly allocated 
to in the 2-period crossover design, either ZLP-PFS followed by ZLP-AI (sequence AB) or 
ZLP-AI followed by ZLP-PFS (sequence BA). Comparisons will be based upon within study 
participant variability. Administration of a single dose with each injection device is an efficient 
and relevant means to evaluate differences in the PK of ZLP delivered by 2 different injection 
devices. 
4.2.1 
Patient input into design 
Not applicable. 
4.3 
Justification for dose 
 
 
 
 
 
 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 19 of 68 
Table 4-1: 
Zilucoplan weight-bracketed dosing 
Actual dose (mg) 
Weight range (kg) 
 
 
 
 
 
 
Note: the weight to be used to determine the actual dose in both periods will be the weight taken at Day -1 of 
Treatment Period 1. 
4.4 
End of study definition 
A participant is considered to have completed the study if they have completed all periods of the 
study, including Treatment Period 1 and Treatment Period 2, and the EOS Visit. 
The global end of the study is defined as the date of the last EOS Visit for the last participant in 
the study. 
5 
STUDY POPULATION 
Fourteen healthy adult male and female participants who meet the required inclusion and 
exclusion criteria will be randomized in this study. 
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 18 to 55 years of age inclusive, at the time of signing the informed 
consent. 
Type of participant and disease characteristics 
2. Participants who are overtly healthy as determined by medical evaluation including medical 
history, physical examination, laboratory tests, and cardiac monitoring. 
3. Participants must be vaccinated with a quadrivalent vaccine and serogroup B vaccine against 
meningococcal infections (N. meningitidis) at least 2 weeks before the first administration of 
IMP if not previously vaccinated within 3 years prior to the start of IMP administration. 
Study participants who are not previously vaccinated may receive Menactra® (quadrivalent 
vaccine) and Bexsero® (serogroup B vaccine) during the Screening Period, 2 weeks prior to 
initiating IMP. 
Weight 
4. Body mass index (BMI) ≥18.5 to ≤30.0kg/m2 at the Screening Visit. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 20 of 68 
Sex 
5. Male and/or female: 
− A male participant must agree to use contraception during the Treatment Period as 
detailed in Appendix 4 of the protocol and for at least 40 days (approximately 
5 half-lives) after the last dose of IMP 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 female/woman of childbearing potential (WOCBP) as defined in Appendix 4 of 
the protocol 
OR 
A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 
(Section 10.4) during the Treatment Period and for at least 40 days (approximately 
5 half-lives), corresponding to time needed to eliminate IMP after the last dose of 
IMP. 
Informed consent 
6. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1), which 
includes compliance with the requirements and restrictions listed in the informed consent 
form and in the protocol. 
5.2 
Exclusion criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
1. Participant has a history of or current significant medical disorder, psychiatric disorder, or 
laboratory abnormality that in the opinion of the Investigator makes the study participant 
unsuitable for participation in the study, including any previous or current cardiovascular, 
respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological 
disorders capable of significantly altering the absorption, metabolism, or elimination of 
drugs; constituting a risk when taking IMP; or interfering with the interpretation of data. 
2. Current or recent systemic infection within 2 weeks before the first administration of IMP or 
infection requiring intravenous antibiotics within 4 weeks before the first administration of 
IMP. 
3. Current history of alcohol or drug use disorder, as defined in Diagnostic and Statistical 
Manual of Mental Disorders V, within the previous 6 months. 
4. Participant has a known hypersensitivity to any components of the IMP or comparative drugs 
(and/or an investigational device) as stated in the protocol. 
Prior/Concomitant therapy 
5. Intended use of over-the-counter or prescription medication, vitamins, herbal/traditional 
medicines (including St John's Wort) or dietary supplements (excluding medicines for 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 21 of 68 
external use), with the exception of those specified in Section 6.5.1, within 2 weeks before 
the first administration of IMP. 
6. Participant has used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, 
isoniazid, phenytoin, rifampicin) within 2 months before the first administration of IMP. 
Prior/Concurrent clinical study experience 
7. 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. 
8. Participant has participated in another study of an IMP (and/or an investigational device) 
within the previous 30 days or 5 half-lives (whichever is longer), or is currently participating 
in another study of an IMP (and/or an investigational device). 
Diagnostic assessments 
9. Participants with clinically relevant abnormalities in a standard 12-lead electrocardiogram 
(ECG) at the Screening Visit as judged by the Investigator. 
10. Presence of hepatitis B surface antigen at the Screening Visit or within 3 months prior to 
dosing. 
11. Positive hepatitis C antibody test result at the Screening Visit or within 3 months prior to 
starting IMP. NOTE: Participants with positive hepatitis C antibody due to prior resolved 
disease can be enrolled if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is 
obtained. 
12. Positive hepatitis C RNA test result at the Screening Visit or within 3 months prior to first 
dose of IMP. NOTE: Test is optional and participants with negative hepatitis C antibody test 
are not required to also undergo hepatitis C RNA testing. 
13. Positive human immunodeficiency virus antibody test at the Screening Visit. 
14. Positive syphilis test at the Screening Visit. 
15. Positive throat swab for N. meningitidis at the Screening Visit or a prior history of 
meningitis. 
Other exclusions 
16. Study participant has donated blood or plasma or has experienced blood loss >400mL within 
90 days, >200mL within 30 days, or has donated any blood or plasma within 2 weeks before 
the first administration of IMP. 
17. Study participant is a current smoker or used nicotine-containing products (eg, tobacco, 
patches, gum) within 30 days before the first administration of IMP. 
18. Participant must abstain from ingesting caffeine- or xanthine-containing products (eg, coffee, 
tea, cola drinks, and chocolate) on Day 1 of each Treatment Period. 
19. Participant tests positive for alcohol breath test at the Screening Visit or on Day -1. 
Participants must abstain from alcohol consumption for at least 24 hours prior to admission at 
the study center in each Treatment Period. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 22 of 68 
20. Study participant has a positive drug test (urine test) at the Screening Visit or on Day -1. 
Participants must abstain from using any recreational drug, medical marijuana, and 
cannabidiol throughout the duration of the study. 
21. Participant must abstain from strenuous exercise throughout the duration of the study. Study 
participants may participate in light recreational activities (eg, watching television, reading). 
22. Participant has any condition that makes a local assessment or injection difficult or not 
possible (eg, skin condition, tattoos, skin burns, nevus, or a missing limb). 
5.3 
Lifestyle restrictions 
There are no lifestyle restrictions during the study. 
5.4 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered 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 (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any serious adverse event (SAE). 
6 
STUDY TREATMENTS/INVESTIGATIONAL DEVICE 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
6.1 
Treatments administered 
The treatment administered in DV0012 is presented in Table 6-1. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 23 of 68 
Table 6-1: 
Treatment administered 
ARM Name 
ZLP-PFS 
ZLP-AI 
Intervention name 
ZLP 
Type 
Drug product (15-amino acid macrocyclic synthetic peptide) associated 
with a functional secondary packaging  
Dose formulation 
Syringe (containing the solution for 
injection) within a needle safety 
device 
Prefilled pen containing the 
solution for injection 
Unit dose strength(s) 
Drug solution 
 
Dosage level(s) 
3 body weight ranges: 
 ZLP 
 ZLP 
 ZLP 
Frequency: once 
Route of administration 
Subcutaneous injection into the abdomen 
Use 
Experimental 
IMP and NIMP 
IMP 
Sourcing 
Provided centrally by the Sponsor 
Packaging and labeling 
Study intervention will be provided in a box that protects from light or 
damage. Each box will be labeled as required per country requirement. 
Excipients  
Isotonic buffered solution of RA101495 sodium (drug substance), 
containing standard excipients 
Current/Former name(s) 
or alias(es) 
RA101495 
AI=auto-injector; IMP=investigational medicinal product; PFS-prefilled syringe; NIMP=non-investigational 
medicinal product ZLP=zilucoplan; ZLP-AI=zilucoplan auto-injector 
The ZLP formulation has been designed for convenient sc injection by daily self-administration 
at home. Zilucoplan injection is currently provided in multiple strengths: 
, 
, and 
. Dose strength variation is accomplished by varying the 
syringe fill volume; each is a 
 solution of ZLP. 
Treatment of the injection site with an anesthetic or other topical products (eg, steroids) prior to 
dosing is not permitted. Additional instructions for device use, including the injection angle, are 
provided in the instructions for use. 
Participants will receive the doses of IMP listed in Table 6-1 based on their weight at Day -1 of 
Treatment Period 1. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 24 of 68 
6.1.1 
Devices 
The ZLP drug product will be supplied as: 
• ZLP-PFS: A sterile, preservative-free aqueous solution prefilled into a syringe within a 
needle safety device. The ZLP-PFS is a single-integral, non-reusable drug-device 
combination product. 
• ZLP-AI: A sterile, preservative-free aqueous solution prefilled into a syringe inside an 
autoinjector. The ZLP-AI-1mL is a single-integral, non-reusable drug-device combination 
product. 
All Adverse Device Effects (serious and nonserious) and device deficiencies (including 
malfunction use error and inadequate labeling) for all devices, shall be documented and reported 
by the Investigator throughout the study (see Section 8.2.8) and appropriately managed by the 
Sponsor. 
6.2 
Preparation, handling, storage, and accountability requirements 
The Investigator or designee must confirm that appropriate temperature conditions have been 
maintained during transit for all study treatment received, and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment and only authorized site staff 
may supply or administer study treatment. All study treatments must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions, with access limited to the Investigator and authorized site staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual. 
The Investigator (or designee) will instruct the participant to store the IMP following the 
instructions on the label. 
Further guidance and information for the final disposition of unused study treatment are provided 
in the IMP Handling Manual. 
6.2.1 
Drug accountability/Device accountability 
The eCRF will be used to record IMP dispensing and return information on a by-participant basis 
and will serve as source documentation during the course of the study. Details of any IMP lost, 
damaged (due to breakage or wastage), not used, partially used, disposed of at the study site, or 
returned to the Sponsor or designee must also be recorded on the appropriate forms. All supplies 
and pharmacy documentation must be made available throughout the study for UCB (or 
designee) to review. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 25 of 68 
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The Investigator must ensure that the IMP is used only in accordance with the protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers/partially used), unused, damaged, and/or expired IMP must be reconciled and either 
destroyed at the site according to local laws, regulations, and UCB standard operating procedures 
(SOPs) or returned to UCB (or designee). Investigational medicinal product intended for the 
study cannot be used for any other purpose than that described in this protocol. 
6.3 
Measures to minimize bias: randomization and blinding 
Randomization will be involved only in the assignment of study participants to the treatment 
sequences as per the crossover design. 
The contract research organization (CRO) or designated vendor will generate the randomization 
lists (a main list and a replacement list) for the treatment sequence allocation. Dummy 
randomization lists will be reviewed by the Clinical Trial Statistician at UCB to ensure that the 
list meets the study requirements. A master randomization list will be produced using a different 
seed by the CRO or vendor. 
In addition to the main randomization list, a replacement randomization list will be provided in 
order to replace withdrawn study participants; the replacement participant will receive the same 
treatment sequence as the corresponding withdrawn participant. 
This is an open-label study; therefore, there is no treatment blind for study participants and 
Investigators at the site. However, in an effort to minimize selection bias, assignment of 
treatment sequence for each study participant will not be revealed to the study participant or 
Investigator prior to the time of dosing on Day 1 of each Treatment Period. Only the site 
pharmacist (and any other designated operational site staff, if deemed necessary) will receive the 
master randomization schedule, and such personnel will be listed in the randomization 
specification. Study participants will be allocated a randomization number in the order that they 
successfully complete Screening assessments, and this number will be used for allocating 
treatment sequences using the randomization schedule. 
6.4 
Treatment compliance 
Drug accountability must be recorded on the Drug Accountability form. 
6.5 
Concomitant medication(s)/treatment(s) 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
The following concomitant medications are permitted during the study: 
• Paracetamol/acetaminophen for the treatment of mild symptoms (eg, headache or other pain), 
given at most every 6 to 8 hours, not exceeding 2g per day, and with a total of no more than 
5g over 7 days. 
• Ibuprofen, not exceeding 1.2g per day. 
• Intranasal corticosteroids for seasonal rhinitis and topical corticosteroids for controlled 
dermatological conditions. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 26 of 68 
• Reliable contraceptives: Oral contraceptives not exceeding 30μg ethinyl estradiol or 
postmenopausal hormone replacement therapy or implants, patches, or intrauterine 
devices/intrauterine systems delivering progesterone (for female study participants). 
The use of concomitant medications to treat AEs should be discussed between the Investigator 
and the Medical Monitor. All concomitant medications necessary for the health and well-being 
of a participant will be permitted. 
6.5.2 
Prohibited concomitant treatments (medications and therapies) 
The following concomitant medications are prohibited during the study: 
• Over-the-counter medications or prescription medications, vitamins, herbal/traditional 
medicines (including St John’s Wort) or dietary supplements (excluding medicines for 
external use), with the exception of those specified in Section 6.5.1, within 2 weeks before 
the first administration of ZLP. 
• Hepatic enzyme-inducing drugs (eg, glucocorticoids [except where permitted in 
Section 6.5.1], phenobarbital, isoniazid, phenytoin, rifampicin) should not be used within 
2 months before the first administration of ZLP. In case of uncertainty, the Medical Monitor 
should be consulted. 
6.5.3 
Rescue medication 
Not applicable. 
6.6 
Dose modification 
No dose modifications are allowed during the study. Study personnel will administer 1 injection 
to the study participant into the abdomen on Day 1 of each Treatment Period. The same dose of 
IMP will be administered for both Treatment Periods. 
6.7 
Criteria for study hold or dosing stoppage 
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity. 
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
Investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The Independent Ethics Committee (IEC) should also be informed and provided 
with reason(s) for the termination or suspension by the Sponsor or by the Investigator/institution, 
as specified by the applicable regulatory requirement(s). In addition, arrangements will be made 
for the return or destruction of all unused IMP and other material in accordance with UCB 
procedures for the study. 
Dosing stoppage for individual participants is not applicable for this study given this is a single 
dose study and the safety experience of ZLP from clinical studies. Refer to the IB for details. 
6.8 
Treatment after the end of the study 
There is no treatment following the end of the study. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 27 of 68 
7 
DISCONTINUATION OF IMP AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of IMP 
Not applicable. 
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 their 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, they 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 for data to be collected at the time of study withdrawal. 
Study participants should be withdrawn from the study if any of the following events occur: 
1. The study participant develops a clinically relevant medical condition (physical 
[eg, meningococcal disease] or psychiatric) that, in the opinion of the Investigator, 
jeopardizes or compromises the study participant’s ability to participate in the study or makes 
it unsafe to continue. 
2. Participant is noncompliant with the study procedures or medications in the opinion of the 
Investigator. 
3. The study participant takes prohibited concomitant medications as defined in this protocol. 
4. The study participant withdraws their consent. 
5. The Sponsor or a regulatory agency requests withdrawal of the study participant. 
6. The study participant has a confirmed positive serum pregnancy test. 
7. The study participant has an anaphylactic reaction after their first injection. 
Investigators should attempt to obtain information on study participants in the case of 
withdrawal. 
Investigators should contact the UCB Medical Monitor, whenever possible, to discuss the 
withdrawal of a study participant in advance. 
7.3 
Lost to follow-up 
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and is unable to be contacted by the study site. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 28 of 68 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (at least 1 phone call and 1 written message 
to the participant), and document their effort (date and summary of the phone call and copy 
of the written message in the source documents), to complete the final evaluation. All results 
of these evaluations and observations, together with a narrative description of the reason(s) 
for removing the participant, must be recorded in the source documents. The eCRF must 
document the primary reason for withdrawal. 
Should the participant continue to be unreachable, they 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 treatment. 
Adherence to the study design requirements, including those specified in the Schedule of 
Activities (Section 1.3), is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The Investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in 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 100mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
8.1 
Pharmacokinetics 
Blood samples of approximately 2 mL will be collected for measurement of plasma 
concentrations of IMP as specified in the Schedule of Activities (Section 1.3) Instructions for the 
collection and handling of biological samples will be provided by the Sponsor or designee. The 
actual date and time (24-hour clock time) of each sample will be recorded. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 29 of 68 
The maximum deviations from scheduled sampling times considered irrelevant for PK are 
defined in Table 8-1. 
Table 8-1: 
Time Windows for PK sampling 
PK blood sampling times 
Maximum deviation from scheduled time 
0 hours (predose) 
Within 60 minutes before dosing 
≤4 hours 
±3 minutes 
6 to 8 hours 
±6 minutes 
12 hours 
±12 minutes 
≥24 to 144 hours 
±30 minutes 
>144 hours 
±60 minutes 
PK=pharmacokinetic 
Each plasma sample will be divided into 2 aliquots (1 each for PK and a backup). Samples 
collected for PK analyses may also be used to evaluate safety or efficacy aspects related to 
concerns arising during or after the study. In addition, surplus PK samples may be stored and 
used for potential future biomarker research (including assay development/optimization), but not 
for future genetic biomarker research. 
8.2 
Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). 
8.2.1 
Adverse events and serious adverse events 
The definitions of device-related safety events, adverse device effects (ADEs) and serious 
adverse device effects (SADEs) can be found in Appendix 7 (Section 10.7). Device deficiencies 
are also addressed in Appendix 7 (Section 10.7). 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
participant to withdraw from the study (see Section 7). 
8.2.2 
Time period and frequency for collecting AE and SAE information 
All AEs and SAEs will be collected from the signing of the ICF until EOS Visit, at the time 
points specified in the Schedule of Activities (Section 1.3). 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the eCRF even if no IMP was taken but specific 
study procedures were conducted. This includes all AEs not present prior to the initial visit and 
all AEs that recurred or worsened after the initial visit. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 30 of 68 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in Appendix 3 (Section 10.3). The Investigator will submit any updated SAE data to the Sponsor 
within 24 hours of it being available. 
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the IMP), up to 
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 IMP must be reported to UCB regardless of the time between the 
event and the end of the study. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3). 
8.2.3 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.2.4 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and non-serious AEs of special interest (as 
defined in Section 8.2.1), will be followed until resolution, stabilization, the Investigator 
determines that it is no longer clinically significant, the event is otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is given in Appendix 3 (Section 10.3). 
8.2.5 
Regulatory reporting requirements for SAEs 
Prompt notification of a SAE by the Investigator to the Sponsor is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IEC, and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. SUSAR reporting will be in adherence to requirements of EU 
pharmacovigilance legislation, CT legislation and guidance, Clinical Trial Regulation EU 
536/2014; CT-3 and all other applicable local regulations. 
An Investigator who receives an Investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 
along with the Investigator’s Brochure and will notify the IEC, if appropriate according to local 
requirements. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 31 of 68 
8.2.6 
Pregnancy 
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study treatment and until 40 days after the last dose of study treatment. 
If a pregnancy is reported, the Investigator must immediately inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 4 
(Section 10.4). 
The participant should be withdrawn from the study as soon as pregnancy is known (by positive 
pregnancy test), and the following should be completed: 
• The participant should return for an EOS Visit. 
• The participant should immediately stop the intake of the IMP or be down-titrated as 
instructed at the EOS Visit. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.2.7 
Adverse events of special monitoring 
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. 
8.2.8 
Device – adverse events (ADEs, UADEs, SAEs, SADEs, and USADEs) 
and device deficiencies 
Devices are being provided for use in this study purposes of sc ZLP dosing (see Section 6.1.1). 
In order to fulfill regulatory reporting obligations worldwide, the Investigator is responsible for 
the detection and documentation of events meeting the definitions of ADEs, SADEs, and device 
deficiency that occur during the study with such devices. 
Adverse events will be reported according to the ISO 14155:2020, while recognizing and 
following requirements including reporting timelines specified in other specific laws, 
regulations, directives, standards and/or guidelines as appropriate and as required by the 
countries in which the clinical investigation is conducted. 
The definition of a ADE, SADE, USADE, an device deficiency can be found in Appendix 7 
(Section 10.7). 
NOTE: Events fulfilling the definition of an AE/SAE will also follow the processes outlined in 
Section 8.2.4 and Appendix 3 of the protocol. 
8.2.8.1 
Time period for detecting ADEs and device deficiencies 
Adverse device effects and device deficiencies or malfunctions of the device that result in a 
reportable event will be detected, documented, and reported during all periods of the study in 
which the device is used. 
If the Investigator learns of any ADEs or device deficiencies at any time after a participant has 
been discharged from the study, and such event(s) is considered reasonably related to a device 
provided for the study, the Investigator will promptly notify the Sponsor. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 32 of 68 
The method of documenting ADEs and device deficiencies is provided in Appendix 7 
(Section 10.7). 
8.2.8.2 
Follow-up of ADEs and device deficiencies 
Follow-up applies to all study participants, including those who discontinue IMP and/or the 
study. 
The Investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
New or updated information will be recorded on the originally completed form with all changes 
signed and dated by the Investigator. 
8.2.8.3 
Prompt reporting of ADEs and device deficiencies to Sponsor 
Adverse device effects and device deficiencies will be reported to the Sponsor within 24 hours 
after the Investigator determines that the event meets the protocol definition of an ADE or device 
deficiency. 
The Sponsor will be the contact for the receipt of device deficiency reports. 
The Adverse Event and Device Deficiency Report Form will be sent to the Sponsor using the 
paper form. Adverse device effects and device deficiency reports will be forwarded to the 
corresponding device manufacturer. The device manufacturer is responsible for the subsequent 
vigilance evaluation and reporting, as applicable. 
8.2.8.4 
Regulatory reporting requirements for ADEs and device deficiencies 
The Investigator will promptly report all ADEs and device deficiencies immediately and under 
no circumstance should this exceed 24 hours for any medical device provided for use in the study 
in order for the Sponsor to fulfill the legal responsibility to notify appropriate regulatory 
authorities and other entities about certain safety information relating to devices being used in 
clinical studies. 
The Investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to the 
reporting of device deficiencies to the IEC. 
8.2.9 
Clinical safety laboratory assessments 
See Appendix 2 for the list of clinical laboratory tests (hematology, clinical chemistry, urinalysis, 
and screening 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 participant's condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or after the last dose of IMP should be repeated until the values return to normal or 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 33 of 68 
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, must be conducted in 
accordance with the laboratory manual and the Schedule of Activities (Section 1.3). 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the Investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the eCRF. 
8.2.10 
Vital signs 
Vital signs (systolic and diastolic blood pressure, pulse rate, and oral body temperature) 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 and pulse measurements should be preceded by at least 5 minutes of rest for the 
participant in a quiet setting without distractions (eg, television, cell phones). 
Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 pulse and 
3 blood pressure measurements (3 consecutive blood pressure readings will be recorded at 
intervals of at least 1 minute). The average of the 3 blood pressure readings will be recorded on 
the eCRF. 
8.2.11 
Electrocardiograms 
12-lead ECG will be obtained at Screening only using an ECG machine that automatically 
calculates the heart rate and measures PR, QRS, QT, and QTc intervals. 
All ECG recordings should be taken with the study participant resting in the supine position for 
at least 5 minutes before the recording. 
Three individual ECG tracings should be obtained as closely as possible in succession, but no 
more than 2 minutes apart. The full set of triplicates should be completed in less than 4 minutes. 
8.2.12 
Physical examination 
A full physical examination will include, at a minimum, general appearance; and a review of 
systems (dermatologic, head, eyes, ears, nose, mouth/throat/neck, thyroid, lymph nodes, 
respiratory, cardiovascular, gastrointestinal, extremities, musculoskeletal, neurologic and 
psychiatric systems). 
A symptom-directed abbreviated physical examination will include, at a minimum, an 
assessment of the general appearance, skin, cardiovascular system, respiratory system, and/or 
abdomen based on the presenting symptoms. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Physical examination findings will be listed, including clinical significance. Clinically significant 
physical examination abnormalities will be reported as AEs. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 34 of 68 
8.3 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that Investigators, clinical study participants, regulatory 
authorities, and IECs will be informed appropriately and as early as possible. 
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs (including device-related SAEs) and perform ongoing SAE reconciliations in 
collaboration with the Patient Safety representative. 
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory or ECG results) for which data will be periodically reviewed during the course 
of the study. 
8.4 
Treatment of overdose 
For this study, any dose of ZLP greater than the intended dose will be considered an overdose. 
Overdose events are only considered AEs or SAEs if there are associated clinical signs and 
symptoms, or if the act of taking the excess IMP 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 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. 
8.5 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.6 
Immunogenicity assessments 
Immunogenicity is not evaluated in this study. 
8.7 
Medical resource utilization and health economics 
Medical resource utilization and 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. 
9.1 
Definition of analysis sets 
The All Study Participants Set will consist of all study participants who signed informed consent. 
The Randomized Set will consist of all study participants who are randomized. Note: This set 
will only be produced if it differs from the Safety Set. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 35 of 68 
The Safety Set will consist of all study participants who are randomized and receive at least 
1 dose of ZLP. Study participants will be classified according to the sequence to which they were 
randomly assigned. 
The Pharmacokinetic Set will consist of all study participants who are randomized, receive at 
least 1 dose of ZLP, and have at least 1 observable PK concentration measurement. 
If a study participant in the PK set is missing individual time points or these are otherwise 
unobservable, the study participant will be included in the PK set but those time points will be 
omitted from the PK summaries, as appropriate. 
Note that some study participants in the PK set may not have a complete set of PK parameters as 
some parameters may not be able to be calculated based on the PK concentrations collected. 
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. 
Baseline is defined as the last nonmissing measurement collected at the first In-Clinic Period 
(Day -1) for both Treatment Periods. 
9.3 
Planned PK analyses 
9.3.1 
Analysis of the primary endpoint 
The primary outcome variable is defined in Table 3-1. 
Pharmacokinetics will be determined by non-compartmental analysis in Phoenix WinNonlin 
using the PK set. 
The PK parameters of ZLP will be computed using the actual blood sampling time points. 
The plasma concentration time profiles and PK parameters of ZLP will be summarized by 
injection device using descriptive statistics. The descriptive statistics will include: n, mean, 
standard deviation, geometric mean and associated 95% confidence interval (CI), geometric 
standard deviation (GeoSD), geometric coefficient of variation (GeoCV), minimum, median, and 
maximum. 
Individual plasma ZLP concentration time profiles will be displayed graphically on a 
linear-linear scale and semi-logarithmic scale (including spaghetti plots). Geometric mean 
plasma concentrations-time curves including their 95% CIs will be displayed by injection device. 
Log-transformed PK parameters of area under the plasma concentration-time curve from time 0 
to infinity (AUC), area under the plasma concentration-time curve from time 0 to time t(AUC0-t), 
and maximum (or peak) observed plasma concentration (Cmax) will be analyzed using a mixed-
effects model with period, treatment and sequence as fixed effects and study participant as a 
random effect. The ZLP-PFS device will be considered the reference for the comparisons. The 
primary analysis to determine if bioequivalence is established will use data from study 
participants who have evaluable primary PK endpoints for both Treatment Periods. If one or 
more study participants do not have evaluable primary PK endpoints for both Treatment Periods, 
an additional analysis, using the same model except with the inclusion of Satterthwaite's 
correction for degrees of freedom, will be carried out using all data available. The least squares 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 36 of 68 
(LS) means and their associated 95% CIs for each treatment, and the difference in LS means and 
its 90% CI between the 2 injection devices (ZLP-AI versus ZLP-PFS) will be estimated from 
both models. All estimates will be back-transformed to provide geometric means and 95% CI for 
each injection device, and the ratio of geometric means (ZLP-AI/ZLP-PFS) and its 90% CI will 
also be provided. Inter- and intra-participant variability of PK parameters will be derived from 
the results of this analysis. 
9.3.2 
Exploratory endpoint analyses 
The exploratory outcome variables are defined in Table 3-1. 
The PK parameters t½, apparent plasma clearance (CL/F), and apparent volume of distribution 
(Vz/F) will be summarized by the injection device using descriptive statistics as for the PK 
parameters described in Section 9.3.1. For the PK parameter tmax, only median, minimum, and 
maximum will be reported. 
9.4 
Planned safety and other analyses 
9.4.1 
Safety analyses 
9.4.1.1 
Secondary endpoint analyses 
The secondary outcome variable is defined in Table 3-1. 
The secondary endpoints in this study are the occurrence of serious adverse events (SAEs), 
treatment-emergent adverse events (TEAEs), and adverse device effects (ADEs, serious and 
nonserious) from Day 1 up to the EOS or ET visit. 
All AEs (including effects associated with the use of the device that fulfil the definition of an 
AE, ie, ADEs) will be coded using the most recent Medical Dictionary for Regulatory 
Activities (MedDRA®) and characterized as pretreatment (prior to the first dose) and 
treatment-emergent according to the administration of ZLP. Treatment-emergent AEs that occur 
in the week between the 2 Treatment Periods (ie, Washout Period) will be assigned as 
treatment-emergent with regards to the treatment in Treatment Period 1. 
The occurrence and incidence of TEAEs and ADEs will be summarized by MedDRA system 
organ class and preferred term, overall and by injection device. The occurrence and incidence of 
TEAEs and ADEs will also be summarized by intensity and TEAEs by relationship to ZLP. Any 
TEAEs leading to discontinuation and SAEs will also be listed. 
Changes from baseline in clinical laboratory tests (hematology, clinical chemistry, and 
urinalysis) are exploratory safety parameters. Further details regarding analyses of these 
endpoints are provided in Section 9.4.1. 
9.4.1.2 
Exploratory endpoint analyses 
Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) and changes from 
Baseline (Day -1 of each Treatment Period) will be summarized by descriptive statistics at each 
time point by injection device. Values outside the reference range will be flagged in the listings. 
Electrocardiograms will be recorded. The raw data will be listed by injection device. Abnormal 
findings for the ECG will be listed. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 37 of 68 
Physical examination findings will be listed, including clinical significance. Clinically significant 
physical examination abnormalities will be reported as AEs. 
9.4.2 
Other analyses 
9.4.2.1 
Exploratory endpoint analyses 
Device presentations are being provided for use in this study. In order to fulfill regulatory 
reporting obligations worldwide, the Investigator is responsible for the detection and 
documentation of events meeting the definitions of incident or malfunction that occur during the 
study with such device presentations. 
− A device deficiency is an inadequacy of a device with respect to its identity, quality, 
durability, reliability, safety, or performance. Device deficiencies include malfunctions, 
use errors, and inadequate labeling. 
− Device deficiencies will be reported via the eCRF; in addition, sites will fill out a product 
quality complaint form; all product quality complaints will be investigated by UCB. 
Device deficiencies will be listed. Summaries will be provided if there are sufficient data. 
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 PK, safety, 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 
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. 
9.6 
Handling of dropouts or missing data 
There will be no special procedures for handling missing data. 
9.7 
Planned interim analysis and data monitoring 
No interim analysis or data monitoring are planned. 
9.8 
Determination of sample size 
The minimum required sample size for PK bioequivalence studies as recommended by the Food 
and Drug Administration (FDA; Statistical Approaches to Establishing Bioequivalence, 2022) is 
12 study participants. 
This study is designed to establish the bioequivalence of ZLP-PFS (reference) and ZLP-AI (test). 
Bioequivalence is established if the 90% CI for the geometric mean ratio is contained entirely 
within the acceptance range of 0.80 to 1.25 for all 3 PK parameters (AUC, AUC0-t, and Cmax). 
The sample size estimation is based on the intra-participant variability observed in UP0115. This 
was a recent study in healthy study participants which included the ZLP-PFS device to estimate 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 38 of 68 
the relative bioavailability when the ZLP-PFS device was used at different injection sites 
(1 group compared the abdomen and thigh, and a second group compared the abdomen and 
upper arm). Since each participant in UP0115 only had 1 injection in the abdomen, the 
intra-participant coefficient of variation (CV)% was estimated by pooling across injection sites. 
The highest intra-participant CV% reported for AUC0-t or Cmax was 7.74% and this was used in 
the sample size calculation. 
Assuming a geometric mean ratio between 0.90 and 1.11, and intra-participant CV% of 7.74%, 
12 study participants (6 study participants per treatment sequence) are required to have evaluable 
primary PK endpoints (AUC, AUC0-t, and Cmax) from the 2 Treatment Periods to have at least 
95% power to establish bioequivalence. 
Therefore, 12 study participants would fulfill FDA requirements and give more than adequate 
power to establish bioequivalence. 
It is not planned to replace study participants who withdraw from the study; rather the number to 
be randomized has been increased to 14, if a dropout rate of 10% is assumed. If more than 
1 study participant withdraws from each treatment sequence, then study participants who 
withdraw may be replaced at the Sponsor’s discretion, and if replaced, the new study participant 
will be allocated to the same treatment sequence as the withdrawn study participant. The new 
study participant would be expected to complete both Treatment Periods. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 39 of 68 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
The study will be conducted under the auspices of an IEC, as defined in local regulations, 
International Council for Harmonisation (ICH)-GCP, and in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki. 
The Investigator/UCB will ensure that an appropriately constituted IEC that complies with the 
requirements of the current ICH-GCP version or applicable country-specific regulations will be 
responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, Informed 
Consent form, Investigator’s Brochure, Investigator’s curriculum vitae (if applicable), 
advertisement (if applicable), and all other participant-related documents to be used for the study 
to the IEC for its review and approval. 
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IEC for the protocol. 
The Investigator will also promptly report to the IEC all changes in the study, all unanticipated 
problems involving risks to participants or others, and any protocol deviations, to eliminate 
immediate hazards to participants. 
The Investigator will not make any changes in the study or study conduct without IEC approval, 
except where necessary to eliminate apparent immediate hazards to the participants. For minor 
changes to a previously approved protocol during the period covered by the original approval, it 
may be possible for the Investigator to obtain an expedited review by the IEC as allowed. 
As part of the IEC requirements for continuing review of approved studies, the Investigator will 
be responsible for submitting periodic progress reports to the IEC (based on IEC requirements), 
at intervals appropriate to the degree of participant risk involved, but no less than once per year. 
The Investigator should provide a final report to the IEC following study completion. 
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
The appropriate IEC will also be informed by the Investigator or the Sponsor, as specified by the 
applicable regulatory requirements in each concerned country. Where applicable, Investigators 
are to provide the Sponsor (or its representative) with evidence of such IEC notification. 
10.1.2 
Financial disclosure 
Insurance coverage will be handled according to local requirements. 
Finance and insurance are addressed in the Investigator and/or contract research organization 
(CRO) agreements, as applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 40 of 68 
10.1.3 
Informed consent process 
Participant’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. 
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the participant in both oral and written form by the Investigator (or 
designee). Each participant will have the opportunity to discuss the study and its alternatives 
with the Investigator. 
Prior to participation in the study, the Informed Consent form should be signed and personally 
dated by the participant, or their legal representative, and by the person who conducted the 
informed consent discussion (Investigator or designee). The participant or their legal 
representative must receive a copy of the signed and dated Informed Consent form. As part of 
the consent process, each participant must consent to direct access to their medical records for 
study-related monitoring, auditing, IEC review, and regulatory inspection. 
If the Informed Consent form is amended during the study, the Investigator (or the Sponsor, if 
applicable) must follow all applicable regulatory requirements pertaining to the approval of the 
amended Informed Consent form by the IEC and use of the amended form. 
The participant may withdraw their consent to participate in the study at any time. A participant 
is considered as enrolled in the study when they have signed the Informed Consent form. An 
eCRF must not be started, nor may any study specific procedure be performed for a given 
participant, without having obtained their written consent to participate in the study. 
10.1.4 
Data protection 
UCB staff (or designee) will affirm and uphold the participant’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the participant number 
assigned at Screening. 
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
participant’s primary medical records that directly concerns this study (including, but not limited 
to, laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a participant’s study participation, and autopsy reports for deaths 
occurring during the study). 
The participant must be informed that their personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IEC members, and by inspectors from regulatory authorities. 
The contract between UCB and study sites specifies responsibilities of the parties related data 
protection, including handling of data security breaches and respective communication and 
cooperation of the parties. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 41 of 68 
Information technology systems used to collect, process, and store study-related data are secured 
by technical and organizational security measures designed to protect such data against 
accidental or unlawful loss, alteration, or unauthorized disclosure or access. 
10.1.5 
Committees structure 
No Data Monitoring Committee will be established for this study. 
10.1.6 
Dissemination of clinical study data 
All Phase 1-4 clinical studies in patients will be registered on ClinicalTrials.gov with results 
posted after completion of the study. 
A plain language summary of the results of all Phase 1-4 clinical studies will be developed and 
shared on UCB’s website. 
UCB is committed to submitting all Phase 2-4 clinical study results, irrespective of outcome, for 
publication in a credible, peer-reviewed journal. While there are some exceptions owing to 
intellectual property considerations in early clinical development, our policy is also to submit 
Phase 1 study results for publication in a peer-reviewed journal wherever possible. 
Due to the small sample size in this study, individual patient-level data cannot be adequately 
anonymized as there is a reasonable likelihood that individual participants could be re-identified. 
For this reason, data from this study cannot be shared. 
10.1.7 
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 eCRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, legible, contemporaneous, original, and 
attributable from source documents; that the safety and rights of participants are being protected; 
and that the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH-GCP, and all applicable regulatory requirements. 
All essential documents must be retained by the Investigator for the minimum retention period 
mandatory under the applicable local laws and regulations. The Investigator will contact UCB 
for authorization prior to the destruction of any study records or in the event of accidental loss or 
destruction of any study records. The Investigator will also notify UCB should he/she relocate or 
move the study-related files to a location other than that specified in the Sponsor’s trial master 
file. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 42 of 68 
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. 
10.1.7.1 
Case report form completion 
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
electronic 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 electronic 
eCRF. 
Detailed instructions will be provided in the eCRF Completion Guidelines. 
10.1.7.2 
Apps 
Not applicable. 
10.1.8 
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). 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, quality of life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area. 
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the Investigator and become a permanent part of the participant’s source documents. The 
Investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent. 
Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee). 
10.1.9 
Study and site start and closure 
The start of recruitment 
The start of recruitment is the first participant’s first visit and is also the start date of the clinical 
study. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 43 of 68 
Study/site termination 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IEC or local 
health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further IMP development 
10.1.10 
Publication policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 44 of 68 
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 treatment administration and/or response evaluation. If a 
local sample is required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make either a study 
treatment decision or response evaluation, the results must be entered into the eCRF. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5.1 and Section 5.2 of the protocol. 
• Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 45 of 68 
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 
Blood Urea 
Nitrogen 
(BUN) 
Potassium 
Aspartate Aminotransferase 
(AST)/ Serum Glutamic-
Oxaloacetic Transaminase 
(SGOT) 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
Alanine Aminotransferase 
(ALT)/ Serum Glutamic-
Pyruvic Transaminase (SGPT) 
Total Protein 
 
Glucose 
(nonfasting) 
Calcium 
Alkaline phosphatase 
 
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) 
• 
Urine alcohol and drug screen (to include at minimum: amphetamines, 
barbiturates, cocaine, opiates, cannabinoids and benzodiazepines) 
• 
Urine human chorionic gonadotropin (hCG) pregnancy test (as needed for 
women of childbearing potential)1 
• 
Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and hepatitis 
C virus antibody or specify other tests) 
The results of each test must be entered into the eCRF. 
NOTES: 
1. Local urine testing will be standard for the protocol unless serum testing is required by local 
regulation or IEC. 
Investigators must document their review of each laboratory safety report. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 46 of 68 
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 IMP, whether or not considered related to the IMP. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of IMP. 
 
Events meeting the AE definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment of the 
Investigator (ie, not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition, including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after IMP administration even though it may have been 
present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either IMP or a concomitant 
medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional overdose 
taken with possible suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae. 
• 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as 
AE or SAE if they fulfill the definition of an AE or SAE. Also, "lack of efficacy" or "failure of 
expected pharmacological action" also constitutes an AE or SAE. 
 
Events NOT meeting the AE definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the Investigator to be more 
severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the study participant’s 
condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 47 of 68 
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 participant was at 
risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 
d. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance, 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(eg, sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Important medical events: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require medical or surgical intervention to prevent 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. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 48 of 68 
Recording and follow-up of AE and/or SAE 
AE and SAE recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the eCRF. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records to 
UCB in lieu of completion of the UCB AE/SAE eCRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by UCB. In 
this case, all participant identifiers, with the exception of the participant number, will be redacted 
on the copies of the medical records before submission to UCB. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with a SAE. Severe is a category utilized for rating the intensity of an 
event; and both AEs and SAEs can be assessed as severe. 
• 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described 
in the definition of 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 (NCI-CTCAE) 
should be used as a supportive standardization instrument to evaluate AEs and SAEs but the final 
intensity grading by the Investigator must be mild, moderate, or severe. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 49 of 68 
Assessment of causality 
• 
The Investigator is obligated to assess the relationship between IMP and each occurrence of each 
AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to IMP administration will be considered and 
investigated. 
• 
The Investigator will also consult the 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 a SAE has occurred and the Investigator has minimal 
information to include in the initial report to UCB. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to UCB. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and 
send a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by UCB to elucidate the nature and/or 
causality of the AE or SAE as fully as possible. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health care 
professionals. 
• 
An AE should be followed until it has resolved, has a stable sequelae, the Investigator determines 
that it is no longer clinically significant, or the participant is lost to follow-up. This follow-up 
requirement applies to AEs, SAEs, and AEs of special interest. 
• 
If a participant dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide UCB with a copy of any 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 the Sponsor within 24 hours of receipt of 
the information. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 50 of 68 
Reporting of SAEs 
SAE reporting to UCB via an electronic data collection tool 
• 
The primary mechanism for reporting a SAE to UCB will be the electronic data collection tool. 
• 
If the electronic system is unavailable for more than 24 hours, then the site will use the paper SAE 
data collection tool (see next section). 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken off-
line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then the 
site can report this information on a paper SAE form (see next section) or to the Medical Monitor 
by telephone. 
• 
Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING section 
at the front of the protocol. 
 
SAE reporting to UCB via paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this information 
to the 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 section 
at the front of the protocol. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 51 of 68 
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 participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
− A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 
− Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception guidance 
Male participants 
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following during the Treatment Period and for at least 40 days after the last 
dose of IMP: 
• 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 WOCBP who is 
not currently pregnant. 
In addition, male participants must refrain from donating sperm for the duration of the study and 
for 40 days after the last dose of IMP. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 52 of 68 
Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration 
during the Treatment Period and for at least 40 days after the last dose of IMP. 
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 the table 
below. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 53 of 68 
Highly effective contraceptive methodsa 
Highly effective contraceptive methods that are user dependentb 
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationc 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 
Highly effective methods that are user independentc 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the partner is the sole 
male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the IMP. 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. 
NOTES: 
a) In case of newly started contraception pills/IUDs, PI 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. 
c) Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the 
efficacy of the contraceptive method. In this case, two highly effective methods of contraception 
should be utilized during the Treatment Period and for at least 40 days after the last dose of IMP. 
Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive urine pregnancy test. 
• Additional pregnancy testing will be performed as described in the Schedule of Activities 
(Section 1.3). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 54 of 68 
• 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 IMP. If the study participant is later found to be on 
placebo, then pregnancy data collection can stop. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 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 the study. 
• The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 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 post-study 
pregnancy-related SAE considered reasonably related to the IMP by the Investigator will be 
reported to the Sponsor as described in Section 8.2.6. While the Investigator is not obligated 
to actively seek this information in former study participants, he or she may learn of a SAE 
through spontaneous reporting. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 55 of 68 
10.5 
Appendix 5: Genetics 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 56 of 68 
10.6 
Appendix 6: Liver safety – suggested actions and follow-up 
assessments 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 57 of 68 
10.7 
Appendix 7: Device adverse events (AEs), adverse device 
effects (ADEs), serious adverse events (SAEs), and device 
deficiencies: Definition and procedures for recording, 
evaluating, follow up, and reporting 
The definitions and procedures detailed in this appendix are in accordance with ISO 14155 and 
the European Medical Device Regulation 2017/745 for clinical device research (if applicable). 
Both the Investigator and the Sponsor will comply with all local medical device reporting 
requirements. 
The detection and documentation procedures described in this protocol apply to all Sponsor 
devices provided for use in the study. See Section 6.1.1 for the list of Sponsor devices. 
10.7.1 
Definitions of AE and ADE 
AE and ADE Definition 
• 
An AE is defined as any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory finding) in study participants, users, or other persons, 
whether or not related to the investigational medical device. This definition includes events related 
to the investigational medical device or comparator and events related to the procedures involved 
except for events in users or other persons, which only include events related to investigational 
devices. 
• 
An adverse device effect (ADE) is defined as an adverse event related to the use of an 
investigational medical device. This definition includes any adverse events resulting from 
insufficient or inadequate instructions for use, deployment, implantation, installation, or operation, 
or any malfunction of the investigational medical device as well as any event resulting from use 
error or from intentional misuse of the investigational medical device. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 58 of 68 
10.7.2 
Definitions of SAE, SADE, and USADE 
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 an AE that: 
a. Led to death 
b. Led to serious deterioration in the health of the participant, that either resulted in: 
1. A life-threatening illness or injury. The term life-threatening in the definition of serious refers 
to an event in which the participant was at risk of death at the time of the event. It does not 
refer to an event which hypothetically might have caused death if it were more severe. 
2. A permanent impairment of a body structure or a body function. 
3. Inpatient or prolonged hospitalization. Planned hospitalization for a pre-existing condition, or a 
procedure required by the protocol, without serious deterioration in health, is not considered a 
SAE. 
4. Medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function. 
c. Led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
SADE definition 
• 
A serious adverse device effect (SADE) is defined as an adverse device effect that has resulted 
in any of the consequences characteristic of a SAE. 
USADE definition 
• 
An unanticipated serious adverse device effect (USADE) is a serious adverse device effect 
which by its nature, incidence, severity, or outcome has not been identified in the current 
version of the risk analysis report (see Section 8.2.8). 
10.7.3 
Definition of device deficiency 
Device deficiency definition 
• 
A device deficiency is an inadequacy of a device with respect to its identity, quality, durability, 
reliability, safety, or performance. Device deficiencies include malfunctions, use errors, and 
inadequate labeling. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 59 of 68 
10.7.4 
Recording and follow up of AE and/or SAE and device deficiencies 
AE, SAE, and device deficiency recording 
• 
When an AE/SAE/device deficiency occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) related to 
the event. 
• 
The Investigator will then record all relevant AE/SAE/device deficiency information in the 
participant’s medical records, in accordance with the Investigator’s normal clinical practice and on 
the appropriate form of the eCRF. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records to 
UCB in lieu of completion of the AE/SAE/device deficiency 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. 
• 
For device deficiencies, it is very important that the Investigator describes any corrective or 
remedial actions taken to prevent recurrence of the deficiency. 
o A remedial action is any action other than routine maintenance or servicing of a medical 
device where such action is necessary to prevent recurrence of a device deficiency. This 
includes any amendment to the device design to prevent recurrence. The Investigator should 
complete a Product Complaint Form for all reported device deficiencies. 
Assessment of intensity 
The Investigator will make an assessment of intensity for each AE/SAE/device deficiency reported 
during the study and assign it to 1 of the following categories: 
• 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with a SAE. Severe is a category utilized for rating the intensity of an 
event, and both AEs and SAEs can be assessed as severe. 
• 
An event is defined as serious when it meets at least 1 of the predefined outcomes as described 
in the definition of a SAE, NOT when it is rated as severe. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 60 of 68 
Assessment of causality 
• 
The Investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE/device deficiency. 
• 
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 intervention administration, will be 
considered and investigated. 
• 
The Investigator will also consult the IB in his/her assessment. 
• 
For each AE/SAE/device deficiency, the Investigator must document in the medical notes that 
he/she has reviewed the AE/SAE/device deficiency and has provided an assessment of causality. 
• 
There may be situations in which a SAE has occurred and the Investigator has minimal 
information to include in the initial report to UCB. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial transmission 
of the SAE data to UCB. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and 
send a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. 
 
Follow up of AE/SAE/device deficiency 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by UCB to elucidate the nature and/or 
causality of the AE/SAE/device deficiency as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other health 
care professionals. 
• 
If a participant dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide UCB with a copy of any postmortem findings, including histopathology. 
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The Investigator will submit any updated SAE data to UCB within 24 hours of receipt of the 
information. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 61 of 68 
10.7.5 
Reporting of SAEs 
SAE reporting to UCB via an electronic data collection tool 
• 
The primary mechanism for reporting a SAE to UCB will be the electronic data collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data collection tool 
(see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken off-
line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then 
the site can report this information on a paper SAE form (see next section) or to the Medical 
Monitor by telephone. 
• 
Contacts for SAE reporting can be found in the SERIOUS ADVERSE EVENT REPORTING 
section at the front of the protocol. 
 
SAE reporting to UCB via paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this information 
to the 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 the SERIOUS ADVERSE EVENT REPORTING 
section at the front of the protocol. 
10.7.6 
Reporting of SADEs 
SADE Reporting to UCB 
NOTE: There are additional reporting obligations for medical device deficiencies that are potentially 
related to SAEs that must fulfill the legal responsibility to notify appropriate regulatory authorities and 
other entities about certain safety information relating to medical devices being used in clinical studies. 
• 
Any device deficiency that is associated with a SAE must be reported to the Sponsor within 
24 hours after the Investigator determines that the event meets the definition of a device 
deficiency. 
• 
The Sponsor shall review all device deficiencies and determine and document in writing whether 
they could have led to a SAE. These shall be reported to the regulatory authorities and IECs as 
required by national regulations. 
• 
Contacts for SAE reporting can be found in the SAFETY REPORTING OF ADVERSE 
EVENTS (SERIOUS AND NONSERIOUS) AND DEVICE DEFICIENCES section at the front 
of the protocol. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 62 of 68 
10.8 
Appendix 8: Rapid alert procedures 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 63 of 68 
10.9 
Appendix 9: Country-specific requirements 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 64 of 68 
10.10 
Appendix 10: Abbreviations and trademarks 
ADE 
adverse device effect 
AE 
adverse event 
C5 
complement component 5 
CI 
confidence interval 
CRO 
contract research organization 
CV 
coefficient of variation 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ET 
early termination 
EOS 
end of study 
GCP 
Good Clinical Practice 
gMG 
generalized myasthenia gravis 
FDA 
Food and Drug Administration 
IB 
Investigator’s Brochure 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IMP 
investigational medicinal product 
IUD 
intrauterine device 
LS 
least squares 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetic(s) 
RNA 
ribonucleic acid 
SADE 
serious adverse device effect 
SAE 
serious adverse event 
sc 
subcutaneous(ly) 
TEAE 
treatment-emergent adverse event 
UADE 
unanticipated adverse device effect 
USADE 
unanticipated serious adverse device effect 
WOCBP 
female/woman of childbearing potential 
ZLP 
zilucoplan 
ZLP-AI 
zilucoplan-autoinjector 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 65 of 68 
ZLP-PFS 
zilucoplan-prefilled syringe 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 66 of 68 
10.11 
Appendix 11: Protocol amendment history 
Not applicable. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 67 of 68 
11 
REFERENCES 
Chamanza R, Marxfeld HA, Blanco AI, Naylor SW, Bradley AE. Incidences and range of 
spontaneous findings in control cynomolgus monkeys (Macaca fascicularis) used in toxicity 
studies. Toxicol Pathol. 2010;38(4):642-57. 
Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016;375(26):2570-81. 
Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic 
strategies. Lancet Neurol. 2015;14(10):1023-36. 
Howard JF Jnr, Bresch S, Genge A, et al. Safety and efficacy of zilucoplan in patients with 
generalized myasthenia gravis (RAISE): a randomized, double-blind, placebo-controlled, phase 3 
study. Lancet Neurol. 2023;22(5):395-406. 
Howard JF Jnr, Vissing J, Gilhus NE, et al. Zilucoplan: An Investigational Complement C5 
Inhibitor for the Treatment of Acetylcholine Receptor Autoantibody-Positive Generalized 
Myasthenia Gravis. Expert Opin Investig Drugs. 2021;30(5):483-493. 
Ramizuddi MK. Review on: Myasthenia gravis and telithromycin-myasthenia crisis. IOSR J 
Dent Med Sci. 2014;13(7):67-97. 
Salari N, Fatahi B, Bartina Y, et al. Global prevalence of myasthenia gravis and the effectiveness 
of common drugs in its treatment: a systematic review and meta-analysis. J Transl Med. 
2021;19(1):516. 
Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of 
myasthenia gravis: Executive summary. Neurology. 2016;87(4):419-25. 
United States Federal Drug Administration (2022). Statistical Approaches to Establishing 
Bioequivalence. https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/statistical-approaches-establishing-bioequivalence-0. 
Vu T, Meisel A, Mantegazza R, et al. Terminal Complement Inhibitor Ravulizumab in 
Generalized Myasthenia Gravis. NEJM Evidence. 2022; 1(5). 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
11 Dec 2023 
Clinical Study Protocol 
Zilucoplan 
DV0012 
 
 
 
Confidential 
Page 68 of 68 
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, according to Clinical Trial Regulation EU 536/2014, 
and according to current Good Clinical Practice. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

Approval Signatures
Name:
dv0012-protocol-ddmmyyyy
Version:
1. 0
Document Number:
CLIN-000241366
Title:
DV0012 - Protocol - Phase 1-Open-label
Approved Date:
14 Dec 2023
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 13-Dec-2023 14:39:58 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 14-Dec-2023 07:54:59 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 14-Dec-2023 14:18:21 GMT+0000
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.