A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Subjects With Amyotrophic Lateral Sclerosis (ALS)
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis, Motor Neuron Disease
Sponsor: Apellis Pharmaceuticals, Inc.

A pellis P har mace uticals, I nc  
Pa ge 1  
 
C o nfi de ntial  
 
 
A P L 2 -A L S - 2 0 6 
 
A P H A S E  2, R A N D O MI Z E D, D O U B L E -B LI N D, 
P L A C E B O- C O N T R O L L E D, M U L TI C E N T E R S T U D Y T O 
E V A L U A T E T H E E F FI C A C Y A N D S A F E T Y O F 
P E G C E T A C O P L A N  I N S U B J E C T S WI T H 
A M Y O T R O P HI C L A T E R A L S C L E R O SI S ( A L S)  
 
 
A M E N D M E N T 6  
 
1 3 J A N U A R Y  2 0 2 3 
 
E u dr a C T n u m ber: 2 0 1 9 - 0 0 3 7 9 7- 1 0 
 
I N D N u m ber: 
 
 
 
C CI

Pegcetacoplan
 
APL2
- ALS
- 206 Protocol Amendment 6
 
13 
January
 202
3 
Apelis Pharmaceuticals, Inc 
Page 
3 
 
Confidential
 
INVESTIGATOR’S AGREMENT
 
 
I have received and read the Investigator’s Brochure for pegcetacoplan. I have read the 
APL2
- ALS
-206 Protocol and agre to conduct the study as outlined. I agre to maintain the 
confidentiality of al information received or developed in conection with this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date
 

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 5 
 
Confidential 
Updated the blinding description 
The open-label treatment period and long-term 
extension is treatment periods are not blinded. 
Synopsis 
Changed language to 
reflect that the new 
long-term treatment 
period is also not 
blinded. 
Updated the statistical methodology for the 
secondary efficacy endpoints. 
Synopsis 
Updated to align with 
Section 12.3 
Added the newly approved medication, Relyvrio. 
Section 4.1  
Relyvrio was recently 
approved for the 
treatment of ALS. 
Updated the study summaries to reflect more 
recent report results. 
Section 4.4  
Updates were needed to 
some of the originally 
presented study 
summaries. 
Added the following paragraph which was from 
the French Addendum 5.1: 
Systemic hypersensitivity reactions (eg, facial 
swelling, rash, urticaria) have occurred in patients 
treated with pegcetacoplan. One patient (less than 
1% in clinical studies) experienced a serious allergic 
reaction which resolved after treatment with 
antihistamines. If a severe hypersensitivity reaction 
(including anaphylaxis) occurs, discontinue 
pegcetacoplan infusion immediately, institute 
appropriate treatment, per standard of care, and 
monitor until signs and symptoms are resolved. 
Section 4.5  
Added to the protocol for 
additional information to 
the study sites, it was 
previously included with 
the French Addendum 5.1, 
Amendment 1. 
Updated the language regarding vaccinations to 
provide further clarity. 
Table 2 (footnote b), 
Section 8.4  
Further clarity was 
needed regarding the 
vaccinations. 
Updated the language regarding anti–
pegcetacoplan peptide antibody and anti-PEG 
antibody collection. 
Table 2 (footnote k), 
Table 3 (footnote i), 
Section 11.1.9  
Updated this language to 
more accurately reflect 
the practice of assessing 
these antibodies. 
Added a new footnote (p) regarding returning 
unused investigational product: 
p 
Only subjects not enrolling in Part 4 will 
return unused investigational product 
Table 3 (footnote p) 
Added to provide further 
instructions to the study 
sites. 
Updated the language in footnote m to provide 
further clarity. 
Table 3 (footnote m) 
Further clarity was 
needed regarding IP 
dispensation. 
Updated the definition of the end of the trial from 
the open-label treatment period to the open-label, 
long-term extension period 
Section 6.5, Section 7.3  
Updated as there is now a 
longer opportunity for 
treatment. 
Updated Section 6.6.6 to be Early Termination 
Follow-Up Visit (previously was Section 6.6.5) 
Created a new Section 6.6.7, Unscheduled Visit(s) 
(previously was Section 6.6.6) 
Section 6.6.6, 
Section 6.6.7  
Sections needed to move 
down due to the addition 
of the new Section 6.6.5 
which describes the new 
open-label long-term 
extension period. 

Pe gcetac o pla n  
A P L 2 -A L S -2 0 6 Pr ot oc ol A me n d me nt 6  
1 3 Ja n uar y 2 0 2 3 
A pellis P har mace uticals, I nc  
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C o nfi de ntial  
Pre vi o us Secti o n 6. 6. 6, U nsc he d ule d Visit(s) has 
bee n m o ve d t o Secti o n 6. 6. 7  
Secti o n  6. 6. 7  
M o ve d t o i nc or p orate 
ne w secti o n.  
A d de d la n g ua ge  re gar di n g s ur vi val stat us f or 
s u bjects w h o wit h dra w fr o m t he st u d y: 
If a s u bject wit h dra ws fr o m t he st u d y, t he n t he 
s u bject a n d/ or t heir care gi vers will be c o ntacte d 
b y t he st u d y site t o pr o vi de p ost -disc o nti n uati o n 
s ur vi val stat us at 6-m o nt h i nter vals u ntil t he st u d y 
c o m pletes.  
Secti o n  7. 3   
A d de d la n g ua ge t o 
c ollect s ur vi val stat us of 
s u bjects w h o ha ve 
wit h dra w n  fr o m t he 
st u d y. 
U p date d t he f oll o wi n g: 
S u bjects are re q uire d t o disc o nti n ue t he 
i n vesti gati o nal pr o d uct a n d wit h dra w fr o m t he 
st u d y if t he y meet t he bel o w criteria: 
•  
A d mi nister a pr o hi bite d  
me dicati o n(s) c o m ple me nt i n hi bit or  
d uri n g t he peri o d o utli ne d i n 
Secti o n  8. 6. 1.  
•  
I nte nti o nall y u n bli n de d t he msel ves. 
Secti o n  7. 3. 1. 1   
U p dat e d  the la n g ua ge t o 
m ore acc uratel y reflect  
t he i nten ti o n of t his 
reas o n f or re q uiri n g a 
s u bject t o wit h dra w. 
A d de d la n g ua ge t o clarif y t hat b ot h ril uz ole a n d 
e dara v o ne ca n n ot be i nitiate d  d uri n g Part 2 of t he 
st u d y.   
Als o, t he f oll o wi n g ne w la n g ua ge was a d de d t o 
t his secti o n: 
•  
S u bjects s h o ul d n ot be gi n Rel y vri o  
( A M X 0 0 3 5) d uri n g Part 2 of t he st u d y 
a n d if a d mi nistere d d uri n g Part 3 or 4, 
t he dates of a d mi nistrati o n m ust be 
d oc u me nte d i n t he s u bject’s s o urce 
d oc u me nt a n d s u bject’s e C R F.  
Secti o n  8. 5   
Clarificati o n nee de d t hat 
ril uz ole a n d e dara v o ne 
are n ot all o we d t o be 
i nitiate d d uri n g Part 2 of 
t he st u d y. 
Rel y vri o  was ne wl y 
a p pr o ve d f or t he treat me nt 
of A L S a n d t his secti o n 
pr o vi des g ui da nce 
re gar di n g if a n d w he n it 
ca n be c o nc o mita ntl y 
a d mi nistere d d uri n g t his 
st u d y 
A d de d t he n u m ber of c ollecti o n ti me p oi nts f or 
t he ne w o pe n-la bel, l o n g-ter m e xte nsi o n peri o d. 
U p d ate d t he sa m ple v ol u me  a m o u nts o ver t he 
c o urse of t he st u d y t o reflect t he a d diti o nal 
c ollecti o n ti me p oi nts .  
Ta ble  5  
U p dates necessar y t o 
reflect t he ne wl y a d de d 
o pe n -la bel, l o n g-ter m 
e xte nsi o n peri o d. 
A d de d t he f oll o wi n g la n g ua ge: 
All deat h e ve nts s h o ul d be re p orte d as t he fatal 
o utc o me of a n S A E, wit h t he date a n d ca use of 
deat h i ncl u de d. T he me dical e ve nt lea di n g t o t he 
s u bject’s deat h (e g, res pirat or y fail ure, 
p ne u m o nia) s h o ul d be re p orte d as t he S A E ter m. 
If n o alter nati ve ca use of deat h is i de ntifie d, 
“ pr o gressi o n of A L S” ma y be re p orte d as t he 
e ve nt ter m if dee me d me dicall y a p pr o priate b y t he 
i n vesti gat or. 
Secti o n  1 1. 2. 1. 3   
T his c ha n ge clarifies t hat 
all deat h e ve nts m ust be 
rec or de d as t he o utc o me 
of a n S A E.  

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 7 
 
Confidential 
Updated language as follows: 
Serious events (including events related to 
efficacy endpoints) that are considered 
ALS-related should be reported as “not related” 
SAEs. “ALS” or “disease progression” should not 
be reported as event terms if a more precise term 
for the , but instead the complication or actual 
cause of hospitalization/death (eg, respiratory 
failure) shouldcan be reported.  
“Disease progression” is considered a worsening 
of a subject’s ALS symptoms (weakness, 
spasticity, respiratory insufficiency, respiratory 
arrest, dysphasia). It may reflect an increase in the 
severity of the disease or an increase in symptoms. 
Any event experienced by a subject which is 
solely regarded as part of disease progression and, 
can be considered as a direct consequence of ALS, 
but does not result in death, should not be reported 
as an AE/SAE; examples include: respiratory 
insufficiency, dysphagia, respiratory failure, 
dysarthria, etc. However, if a subject should 
experience worsening of ALS-related disease 
symptoms that are not considered anticipated 
disease progression for that given subject, the 
investigator should report these findings as an AE. 
Examples of this might include: pneumonia, 
malnutrition, fall, or aspiration. If there is any 
uncertainty as to whether an event is due to 
anticipated disease progression, it should be 
reported as an AE. 
Section 11.2.1.3.1  
These changes reflect the 
update made in 
Section 11.2.1.3 and 
provide further 
clarification regarding 
adverse events associated 
with ALS disease 
progression. 
Updated language as follows: 
The intent-to-treat (ITT) set will include all 
randomized subjects who receive at least one dose 
of randomized treatment (pegcetacoplan or 
placebo). Subjects will be analyzed according to 
their assigned treatment, regardless of the 
treatment actually received. 
Section 12.2.3  
Updated to clarify the 
ITT population more 
accurately. 
Updated language as follows: 
The primary efficacy analysis for the primary 
endpoint (CAFS) will be conducted on the mITT 
set and will be repeated for the ITT and PP sets to 
evaluate the robustness of the results from the 
primary analysis 
Section 12.3.1  
Updated to align with the 
SAP. 

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 8 
 
Confidential 
Updated Section 12.3.2 language as follows: 
(2nd, 3rd, and 4th paragraphs of Section 12.3.2) 
Absolute values and changes from baseline in 
secondary efficacy endpoints (ALSFRS-R, in-clinic 
percentage of predicted SVC, HHD, and 
ALSAQ-40) will be summarized, using descriptive 
statistics, by treatment and visit. Baseline will be 
taken as the measurement closest, but prior, 
to randomizationthe first dose of investigational 
product. 
Changes from baseline in secondary efficacy 
outcomes (ALSFRS-R, in-clinic percentage of 
predicted SVC, HHD, and ALSAQ-40) will be 
summarized by treatment group and analyzed using 
a mixed model for repeated measures repeated 
measurements analysis of covariance. The model 
will include fixed categorical effects for treatment, 
study visit, and the study visit-by-treatment 
interaction, as well as the continuous, fixed covariate 
of baseline and the visit-by-baseline interaction term, 
time from symptoms onset to the first dose of 
investigational product, and the randomization 
stratification factors. Initially an unstructured 
covariance matrix will be investigated. If this 
analysis fails to converge, other covariance 
structures will be used; details will be provided in the 
SAP. The Kenward-Roger approximation will be 
used to estimate denominator degrees of freedom. 
For the secondary endpoints of time to death and 
time to death, permanent tracheostomy, 
or permanent assisted ventilation, Kaplan-Meier 
analysis will be used to describe the survival data. 
The comparison of the survival time between 
treatment groups will be provided using a Cox 
proportional hazard model adjusting for the same 
covariates used in CAFS ANCOVA. For subjects 
who did not experience an event, the time to event 
will be censored at the last observation date for 
the Kaplan-Meier plot. Subjects who were 
randomized but did not receive any treatment will 
be censored at the randomization date. Subjects 
who are lost to follow-up or who discontinued the 
study will be censored at the date of 
discontinuation or lost to follow-up date. 
Section 12.3.2  
Updated to provide more 
clarity and to align with 
the SAP. 

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 9 
 
Confidential 
Updated Section 12.3.3 language as follows: 
Absolute values and changes from baseline in 
exploratory endpoints (EQ 5D 5L, ZBI, at home 
%SVC, NfL, pNfH, and EIM) will be 
summarized, using descriptive statistics, by 
treatment and visit: 
• 
EQ-5D-5L, ZBI, NfL, pNfH, and 
EIM at weeks 52, 104, and 156).  
• 
At-home %SVC at weeks 52 and 
104 
• 
ALSFRS-R, % SVC in-clinic, HHD, 
and ALSAQ-40 at week 156 
Baseline will be taken as the measurement closest 
to but prior to randomization, with the exception 
of at home %SVC, for which baseline is the first 
assessment (which may be done after the first 
dose of study treatment). Time to percutaneous 
endoscopic gastrostomy tube placement up to 
weeks 52, 104, and 156 will be computed and 
summarized by treatment group., as will time to 
death, permanent tracheostomy, or permanent 
assisted ventilation up to week 156; and time to 
death up to week 156. Additional analyses might 
be performed for these endpoints and will be 
detailed in SAP. 
Section 12.3.3  
Updated due to the 
addition of the new 
exploratory endpoints. 
Updated the amendment history to include the 
summary of changes from Amendment 5. 
Appendix 1  
Change made for 
accuracy. 
 

Pe gcetac o pla n  
A P L 2 -A L S -2 0 6 Pr ot oc ol A me n d me nt 6  
1 3 Ja n uar y 2 0 2 3 
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Pa ge 1 0   
 
C o nfi de ntial  
1.  
S Y N O P SI S  
N a me of S p o ns or/ C o m p a n y:  
A pellis P h ar m ace utic als, I nc.  
N a me of Acti ve S u bst a nce:  
Pe gcetac o pla n (als o k n o w n as A P L - 2) 
Pr ot oc ol N u m ber:  
A P L 2 -A L S - 2 0 6 
P h ase:  
2  
 
Title of St u d y:  
A p hase  2, ra n d o mize d, d o u ble-bli n d, place b o -c o ntr olle d, m ultice nter st u d y t o e val uate t he efficac y 
a n d safet y of pe gcetac o pla n i n s u bjects wit h a m y otr o p hic lateral scler osis ( A L S)  
St u d y peri o d:  
Esti mate d 4 5 m o nt hs  
O bjecti ves  
Pri m ar y O bjecti ve: T o assess t he efficac y of t wice per wee k s u bc uta ne o us ( S C) d oses of 
pe gcetac o pla n 1 0 8 0 m g c o m pare d t o place b o i n s u bjects wit h s p ora dic A L S as meas ure d b y t he 
C o m bi ne d Assess me nt of F u ncti o n a n d S ur vi val ( C A F S) ra n k sc ore (j oi nt-ra n k sc ore) 
Sec o n d ar y O bjecti ves:   
•  
T o assess t he effect of pe gcetac o pla n  c o m pare d t o place b o as meas ure d b y t he Re vise d 
A L S F u ncti o nal Rati n g Scale ( A L S F R S -R) sc ore  
•  
T o assess t he effect of pe gcetac o pla n c o m pare d t o place b o o n disease pr o gressi o n as 
meas ure d b y res pirat or y f u ncti o n t hr o u g h perce nta ge of sl o w vital ca pacit y ( % S V C)  
•  
T o deter mi ne t he e ffect of pe gcetac o pla n c o m pare d t o place b o o n m uscle stre n gt h as 
meas ure d b y ha n d hel d d y na m o metr y ( H H D) 
•  
T o deter mi ne t he effect of pe gcetac o pla n c o m pare d t o place b o o n s ur vi val or s pecifie d 
state of disease pr o gressi o n 
•  
T o assess t he ef fect of pe gcetac o pla n c o m pare d t o place b o o n healt h- relate d q ualit y of life 
as meas ure d b y A L S Assess me nt Q uesti o n naire ( A L S A Q - 4 0) 
•  
T o assess t he safet y of pe gcetac o pla n d uri n g t he ra n d o mize d a n d o pe n -la bel treat me nt 
peri o ds t hr o u g h i nci de nce a n d se verit y o f treat me nt-e mer ge nt a d verse e ve nts ( T E A Es), 
cli nical la b orat or y tests ( he mat ol o g y, c he mistr y), vital si g ns, a n d p h ysical e xa mi nati o ns  
•  
T o assess t he l o n g -ter m efficac y of pe gcetac o pla n usi n g A L S F R S-R, % S V C, H H D, 
a n d A L S A Q - 4 0 d uri n g t he o pe n-la bel treat me nt peri o d 
 

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 11 
 
Confidential 
Endpoints 
Primary Efficacy Endpoint: 
• 
CAFS rank score (joint-rank score) at week 52 
Secondary Efficacy Endpoints: 
• 
Change from baseline in ALSFRS-R at week 52 
• 
Change from baseline in %SVC (at clinic visits) at week 52  
• 
Change from baseline in HHD megascore at week 52 
• 
Time to death, permanent tracheostomy, or permanent assisted ventilation up to 
week 52 
• 
Time to death up to week 52 
• 
Change from baseline in ALSAQ-40 at week 52 
• 
Change from baseline of the randomized treatment period (visit 2) and of the 
open-label treatment period (visit 15) to week 104 for ALSFRS-R, %SVC, HHD, and 
ALSAQ-40 
• 
Time to death, permanent tracheostomy, or permanent assisted ventilation up to 
week 104 
• 
Time to death up to week 104 
Primary Safety Endpoints: 
• 
Incidence and severity of TEAEs 
• 
Change from baseline in vital signs and clinical laboratory tests 
• 
Positive responses (Yes) to the Columbia Suicide Severity Rating Scale 

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 12 
 
Confidential 
Exploratory Endpoints: 
• Change from baseline in European Quality of Life–5 Dimensions–5 Level at 
week 52, week 104, and week 156 
• 
Change from baseline in Zarit Burden Interview score at week 52, week 104, 
and week 156 
• 
Change from baseline of %SVC (home spirometry) at week 52 and week 104 
• 
Time to percutaneous endoscopic gastrostomy tube placement up to week 52, 
week 104, and week 156 
• 
Change from baseline in serum neurofilament light chain at week 52, week 104, 
and week 156 
• 
Change from baseline in serum phosphorylated neurofilament heavy chain at week 52, 
week 104, and week 156 
• 
Change from baseline in electrical impedance myography at week 52, week 104, 
and week 156 (only at select investigational sites chosen to complete this) 
• 
Pegcetacoplan pharmacokinetic concentrations at week 52, week 104, and week 156 
• 
Changes from baseline at week 52, week 104, and week 156 in complement 
biomarkers: 
− 
Classical hemolytic complement pathway activity  
− 
Alternative hemolytic complement pathway activity  
− 
C3 levels 
• 
Immunogenicity: presence of antibodies to polyethylene glycol moiety and peptide 
moiety of pegcetacoplan during the randomized and open-label treatment periods 
• 
Change from baseline of the randomized treatment period (week 1) and of the 
open-label treatment period (week 52) to week 156 for ALSFRS-R, %SVC (in-clinic), 
HHD, and ALSAQ-40 
• 
Time to death, permanent tracheostomy, or permanent assisted ventilation up to 
week 156 
• 
Time to death up to week 156  

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 13 
 
Confidential 
Study Design: 
This is a phase 2, randomized, double-blind, placebo-controlled, multicenter, efficacy and safety study 
of SC pegcetacoplan 1080 mg twice per week conducted in approximately 228 subjects with ALS. 
The planned length of participation in the study for each subject is a maximum of approximately 
168 weeks. This study will consist of 5 parts:  
• 
Part 1: Up to 6-week screening period 
• 
Part 2: 52-week randomized treatment period 
• 
Part 3: 52-week open-label (pegcetacoplan) treatment period 
• 
Part 4: 52-week open-label long-term extension treatment period 
• 
Part 5: 6-week off-treatment follow-up period 
Part 1 
Screening (Up to 6 Weeks) 
• 
Informed consent will be obtained at screening prior to any study-related procedures being 
conducted 
• 
Subjects (and/or caregiver) will be trained on the use of at-home assessments. 
Part 2 
Randomized Treatment Period (52 Weeks) 
• 
Approximately 228 subjects who meet all of the inclusion criteria and none of the 
exclusion criteria will be randomized 2:1 to either the pegcetacoplan treatment group or to 
the placebo treatment group. Safety and efficacy will be assessed and will include once per 
week at-home measurements, monthly calls, and clinic visits.  
• 
Pegcetacoplan treatment group  
− 
Subjects randomized to pegcetacoplan will receive SC pegcetacoplan 1080 mg twice 
per week for 52 weeks.  
• 
Placebo treatment group 
− 
Subjects randomized to placebo will receive SC placebo twice per week for 52 weeks.  
Subjects who discontinue treatment early and do not complete Part 2 will continue to Part 5. 
Part 3 
Open-Label (Pegcetacoplan) Treatment Period (52 weeks) 
At the end of Part 2, all subjects from both treatment groups will continue to Part 3. All subjects 
participating in Part 3 will be treated with pegcetacoplan 1080 mg twice per week up to week 104. 
Subjects who complete Part 3 will enter Part 4. Subjects who do not continue to Part 3, or who have 
started Part 3 but discontinue treatment early, will continue to Part 5. 
Part 4 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period (52 weeks) 
At the end of Part 3, any subject who, in the opinion of the investigator, is experiencing clinical benefit 
from pegcetacoplan administration will be invited to continue to Part 4, the open-label long-term 
extension treatment period. All subjects participating in Part 4 will be treated with pegcetacoplan 
1080 mg twice per week up to week 156. Subjects who complete Part 4 will enter Part 5. Subjects who 
do not continue to Part 4, or who have started Part 4 but discontinue treatment early, will continue to 
Part 5. 

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 14 
 
Confidential 
Part 5 
Off-Treatment Follow-up Period (6 weeks) 
During Part 5, all subjects who have discontinued the investigational product (blinded 
pegcetacoplan/placebo or open-label pegcetacoplan) will complete a follow-up visit 6 weeks later. 
Diagnosis: Subjects with a diagnosis of sporadic ALS 
Main Criteria for Inclusion: 
1. Sporadic ALS diagnosed as definite, probable, or laboratory-supported probable as defined 
by the revised El Escorial criteria (Brooks et al. 2000)  
2. At least 18 years of age 
3. Slow vital capacity ≥60% of the predicted value at screening 
4. Onset of ALS symptoms within 72 weeks prior to screening 
5. Total ALSFRS-R score of ≥30 at screening 
6. Women of childbearing potential defined as any woman who has experienced menarche 
and who is NOT permanently sterile or postmenopausal  
a. must have a negative pregnancy test at screening and  
b. must agree to use protocol defined methods of contraception for the duration of the 
study and 90 days after their last dose of investigational product. 
i. Postmenopausal is defined as 12 consecutive months with no menses 
without an alternative medical cause. 
7. Males must agree to 
a. use protocol defined methods of contraception and  
b. refrain from donating sperm for the duration of the study and 90 days after their 
last dose of investigational product. 
8. Have vaccination against Streptococus pneumoniae
, Neiseria meningitidis
 (types A, C, 
W, Y, and B), and Haemophilus influenzae
 (type B) either within 5 years prior to baseline 
visit 2b, or agree to receive vaccination at least 7 days prior to baseline visit 2b. 
Vaccination is mandatory, unless documented evidence exists that subjects are 
nonresponders to vaccination (as evidenced by titers or display titer levels within 
acceptable local limits). 
9. Willing and able to give informed consent and comply with study procedure and 
assessments (including at-home assessments) 

Pegcetacoplan 
APL2-ALS-206 Protocol Amendment 6 
13 January 2023 
Apellis Pharmaceuticals, Inc 
Page 15 
 
Confidential 
Main Criteria For Exclusion: 
1. Confirmed or suspected other causes of neuromuscular weakness 
2. Diagnosis of another neurodegenerative disease(s)  
3. Subject with significant cognitive impairment, clinical dementia, or psychiatric illness that 
in the opinion of the investigator may increase subject’s risk by participating in the study 
or confound the outcome of the study 
4. Subjects with a significant pulmonary disorder not attributed to ALS or who require 
treatments that might complicate the evaluation of the effect of ALS on respiratory 
function (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, 
pulmonary arterial hypertension) 
5. Current use or anticipated need, in the opinion of the investigator, of a diaphragm pacing 
system during the randomized treatment period 
6. Riluzole initiation or change in dose within 30 days prior to the start of the screening 
period or planned initiation during study participation. If using riluzole, the subject should 
remain on the drug throughout Part 2 of study participation, but the dosage may be altered 
or the drug discontinued at any time by the investigator for any safety concern. 
Riluzole-naïve subjects are allowed in the study. 
7. Edaravone initiation or change in dose within 60 days prior to the start of the screening 
period or planned initiation during study participation. If using edaravone, the subject 
should remain on the drug throughout Part 2 of study participation, but the dosage may be 
altered or the drug discontinued at any time by the investigator for any safety concern. 
Edaravone-naïve subjects are allowed in the study. 
8. Positive response to Item 4 or 5 of the Columbia Suicide Severity Rating Scale 
9. Subjects with detectable hepatitis C by polymerase chain reaction at screening 
10. Subjects with chronic inactive hepatitis B with viral loads >1000 IU/mL (>5000 
copies/mL) at screening. Eligible subjects who are chronic active carriers (≤1000 IU/mL) 
must receive prophylactic antiviral treatment according to local country guidelines 
(eg, entecavir, tenofovir, lamivudine) 
11. History of an aggressive lymphoma or presence of a lymphoma requiring therapy by itself 
12. Active or overt malignant disease other than basal cell carcinoma or cutaneous squamous 
cell carcinoma 
13. Received organ transplant 
14. Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase, 
aspartate aminotransferase, or bilirubin levels >2 × the upper limit of normal  
15. Presence or suspicion of severe recurrent or chronic infections that, in the opinion of the 
investigator, increase the subject’s risk by participating in the study 

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16. Participation in any other investigational drug trial or exposure to other investigational 
agent, device, or procedure within 30 days or within 5-half lives of the treatment 
(whichever is longer) prior to the start of the screening period or during study participation 
17. Use of any other complement inhibitor within 30 days or within 5-half lives of the treatment 
(whichever is longer) prior to the start of the screening period or during study participation 
18. If breastfeeding, unwilling to discontinue for the duration of the study and for at least 
6 months after final dose of drug 
19. Inability to cooperate or any condition that, in the opinion of the investigator, could increase 
the subject’s risk by participating in the study or confound the outcome of the study 
20. Subjects with known allergy or hypersensitivity to pegcetacoplan or to any of the components 
21. Known or suspected hereditary fructose intolerance 
Investigational Product, Dosage, and Mode of Administration:  
• 
Pegcetacoplan, 1080 mg twice per week, SC 
• 
Placebo, twice per week, SC 
Duration of Treatment:  
168 weeks total (screening: up to 6 weeks; randomized treatment: 52 weeks; open-label 
[pegcetacoplan] treatment: 52 weeks; open-label [pegcetacoplan] long-term extension period: 
52 weeks; follow-up: 6 weeks) 
Blinding: 
This is a double-blind study during the randomized treatment period. The open-label and long-term 
extension treatment periods are not blinded.  

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Statistical Methodology for Primary Efficacy Endpoint:  
The primary efficacy endpoint is the CAFS rank score (joint-rank score) at week 52.  
The CAFS ranks score will be summarized by treatment group using descriptive statistics. 
The CAFS ranks score will be analyzed using analysis of covariance (ANCOVA) model with 
treatment as a fixed effect, adjusted for baseline ALSFRS-R total score, duration from symptoms 
onset to the first dose of study treatment, and stratification factors. 
Statistical Methodology for Secondary Efficacy Endpoints:   
To preserve the Type 1 error, a fixed-sequence testing strategy will be used. The ordering of the 
secondary endpoints in this testing strategy will match the order in which they are presented in the 
secondary endpoint section.  
Changes from baseline in secondary efficacy outcomes will be summarized by treatment group and 
analyzed using a mixed model for repeated measures repeated measurements. The model will 
include fixed categorical effects for treatment, study visit, and the study visit-by-treatment 
interaction, as well as the continuous, fixed covariate of baseline and the visit-by-baseline 
interaction term, time from symptoms onset to the first dose of investigational product, and the 
randomization stratification factors. Initially, an unstructured covariance matrix will be 
investigated. If this analysis fails to converge, other covariance structures will be used; details will 
be provided in the statistical analysis plan. The Kenward-Roger approximation will be used to 
estimate denominator degrees of freedom. 
For the secondary endpoints of time to death and time to death, permanent tracheostomy, or permanent 
assisted ventilation, Kaplan-Meier will be used to describe the survival data. The comparison of the 
survival time between treatment groups will be provided using a Cox proportional hazard model 
adjusting for the same covariates used for the CAFS ANCOVA. For subjects who did not experience an 
event, the time to event will be censored at the last observation date for the Kaplan-Meier plot. Subjects 
who are lost to follow-up or discontinue study will be censored at the date of discontinuation or lost to 
follow-up. 

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Planned Interim Analysis: 
No interim analysis is planned. 
Statistical Methodology for Safety Endpoints:   
All safety measures, including AEs and clinical laboratory results (hematology, chemistry if 
appropriate), will be descriptively summarized by treatment group at baseline and for each 
postbaseline visit. 
The number and percentage of subjects with TEAEs will be presented. Treatment-emergent 
adverse events are defined as adverse events (AEs) that start or deteriorate on or after the date of 
the first dose of investigational product until the study follow-up visit or the early termination 
follow-up visit.  
Pharmacokinetic concentration will be summarized by treatment group and visit using descriptive 
statistics. 
Sample Size Justification: 
A sample size of 180 randomized subjects (2:1 allocation ratio to pegcetacoplan:placebo) would 
provide approximately 86% power to detect a significant difference (33%) in the primary outcome 
(CAFS score) between the 2 treatment groups at a 2-sided alpha of 5% with 75% power to detect a 
35% improvement in the rate of decline in the ALSFRS-R score and 39% power to detect a 10% 
improvement in survival.  
The estimates were based on the following assumptions: 
• 
Mean monthly rate of decline in ALSFRS-R is 1 unit for the placebo treatment group 
and pooled standard deviation of 0.84 units/month 
• 
52-week mortality rate with placebo at 20% 
• 
Approximately 40-week subject enrollment period 
• 
52 weeks of follow-up for assessing survival outcomes after each subject enrolls 
• 
52 weeks of follow-up for assessing functional outcomes after each subject enrolls 
Subjects will be randomized and stratified by location of first muscle weakness (limb or bulbar) 
and riluzole and edaravone use. 
Approximately 228 subjects (152:76) will be randomized to account for an anticipated 20% of 
randomized subjects prematurely discontinuing the study without providing a postbaseline 
ALSFRS-R measurement. 
 

Pe gcetac o pla n  
A P L 2 -A L S -2 0 6 Pr ot oc ol A me n d me nt 6  
1 3 Ja n uar y 2 0 2 3 
A pellis P har mace uticals, I nc  
Pa ge 1 9   
 
C o nfi de ntial  
2.  
T A B L E O F C O N T E N T S  
TI T L E P A G E  ................................................................................................................................... 1 
SI G N A T U R E P A G E  ....................................................................................................................... 2 
I N V E S TI G A T O R’ S A G R E E M E N T ............................................................................................... 3 
A M E N D M E N T 6: S U M M A R Y O F C H A N G E S F R O M T H E P R E VI O U S V E R SI O N  ................ 4 
1.  
S Y N O P SI S  ................................................................................................................. 1 0 
2.  
T A B L E O F C O N T E N T S  ........................................................................................... 1 9 
LI S T O F T A B L E S  ......................................................................................................................... 2 5 
LI S T O F FI G U R E S  ....................................................................................................................... 2 5 
3.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S ............................. 2 6 
4.  
I N T R O D U C TI O N ...................................................................................................... 2 8 
4. 1.  
A m y otr o p hic Later al Scler osis a n d U n met Me dical Nee d  ......................................... 2 8 
4. 2.  
I nf or mati o n o n t he I n v esti gati o nal Pr o d uct ( Pe gcet ac o pla n) ..................................... 2 8 
4. 3.  
St u d y Rati o nale ........................................................................................................... 2 9  
4. 4.  
S u m mar y of Cli nical E x perie nce Wit h Pe gcet ac o pla n  ............................................... 3 0 
4. 4. 1.  D o se Rati o nale ...................................................................................................... 3 1 
4. 5.  
Cli nical Ris ks/ Be nefits of Pe gcetac o pla n  ................................................................... 3 1 
4. 5. 1.  Safet y Meas ur es Wit h E nr oll me nt  ........................................................................ 3 2 
4. 5. 2.  C O VI D - 1 9 Ris k Miti gati o n Meas ures .................................................................. 3 3 
5.  
T RI A L O BJ E C TI V E S A N D E N D P OI N T S  ............................................................... 3 4 
5. 1.  
O bjecti ves  ................................................................................................................... 3 4 
5. 1. 1.  Pri mar y O bjecti ve  ................................................................................................. 3 4 
5. 1. 2.  Sec o n dar y O bj ecti ves  ........................................................................................... 3 4 
5. 2.  
E n d p oi nts .................................................................................................................... 3 4  
5. 2. 1.  Pri mar y Efficac y E n d p oi nt ................................................................................... 3 4  
5. 2. 2.  Sec o n dar y Efficac y E n d p o i nts .............................................................................. 3 4 
5. 2. 3.  
Pri mar y Safet y E n d p oi nts  ....................................................................................... 3 5 
5. 2. 4.  
E x pl orat or y E n d p oi nts  ........................................................................................... 3 5 
6.  
I N V E S TI G A TI O N A L P L A N ..................................................................................... 3 7 
6. 1.  
O verall St u d y Desi g n .................................................................................................. 3 7  
6. 1. 1.  Part  1: Scree ni n g Peri o d ( U p t o 6 Wee ks) ............................................................ 3 7 
6. 1. 2.  Part  2: Ra n d o mize d Treat me nt Peri o d ( 5 2 Wee ks) .............................................. 3 7 

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6.1.2.1. 
Pegcetacoplan Treatment Group ...............................................................37 
6.1.2.2. 
Placebo Treatment Group .........................................................................37 
6.1.3. 
Part 3: Open-Label (Pegcetacoplan) Treatment Period (52 Weeks) ....................38 
6.1.4. 
Part 4: Open-Label (Pegcetacoplan) Long-Term Extension Treatment 
Period (52 Weeks) ..........................................................................................38 
6.1.5. 
Part 5: Off-Treatment Follow-up Period (6 Weeks) .............................................38 
6.2. 
Number of Subjects ....................................................................................................38 
6.3. 
Treatment Assignment ................................................................................................38 
6.4. 
Criteria for Study Termination ...................................................................................38 
6.5. 
End of Trial Definition ...............................................................................................47 
6.6. 
Study Procedures ........................................................................................................47 
6.6.1. 
Screening Period: Visit 1 ......................................................................................47 
6.6.2. 
Baseline: Visit 2a and Visit 2b .............................................................................48 
6.6.2.1. 
Baseline: Visit 2a ......................................................................................48 
6.6.2.2. 
Baseline: Visit 2b ......................................................................................49 
6.6.3. 
Randomized Treatment Period (Core) Visits .......................................................50 
6.6.3.1. 
Randomized Treatment Period (Core)—Clinic Visits: Visits 3, 5, 
8, 11, 15 ....................................................................................................50 
6.6.3.2. 
Randomized Treatment Period (Core)—Home Assessments ...................51 
6.6.3.3. 
Randomized Treatment Period (Core)—Telephone Visits: 
Visits 4T, 6-7T, 9-10T, 12-14T ................................................................52 
6.6.3.4. 
Follow-Up (Core) Visit: Visit 15b ............................................................52 
6.6.4. 
Open-Label (Pegcetacoplan) Treatment Period Visits .........................................53 
6.6.4.1. 
Open-Label (Pegcetacoplan) Treatment Period—Clinic Visits: 
Visits 16, 21, 28 ........................................................................................53 
6.6.4.2. 
Open-Label (Pegcetacoplan) Treatment Period—Home 
Assessments ..............................................................................................55 
6.6.4.3. 
Open-Label (Pegcetacoplan) Treatment Period—Telephone 
Visits: Visits 17T-20T, 22T-27T ..............................................................55 
6.6.4.4. 
Open-Label (Pegcetacoplan) Treatment Period—Follow-up Visit: 
Visit 28b....................................................................................................55 
6.6.5. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period ...............56 
6.6.5.1. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment 
Period—Clinic Visits: Visits 31, 36, 41 ...................................................57 

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6.6.5.2. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment 
Period—Home Assessments .....................................................................58 
6.6.5.3. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment 
Period—Telephone Visits: Visits 29T, 30T, 32T-35T, 37T-40T .............58 
6.6.5.4. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment 
Period—Follow-up Visit: Visit 41b ..........................................................58 
6.6.6. 
Early Termination Follow-Up Visit ......................................................................59 
6.6.7. 
Unscheduled Visit(s) ............................................................................................61 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................62 
7.1. 
Subject Inclusion Criteria ...........................................................................................62 
7.2. 
Subject Exclusion Criteria ..........................................................................................62 
7.3. 
Subject Completion and Withdrawal Criteria.............................................................64 
7.3.1. 
Reasons for Discontinuation .................................................................................64 
7.3.1.1. 
Mandatory Study Discontinuation/Withdrawal Criteria ...........................65 
7.3.2. 
Subjects “Lost to Follow-up” Prior to Last Scheduled Visit ................................65 
8. 
TREATMENT OF SUBJECTS ..................................................................................66 
8.1. 
Identity of the Investigational Product .......................................................................66 
8.2. 
Treatment Assignment ................................................................................................66 
8.2.1. 
Blinding the Treatment Assignment .....................................................................66 
8.2.2. 
Randomization ......................................................................................................66 
8.2.3. 
Unblinding Prior to Study Completion .................................................................67 
8.3. 
Dosing of the Investigational Product ........................................................................67 
8.4. 
Vaccinations ...............................................................................................................67 
8.4.1. 
Prophylactic Antibiotics .......................................................................................68 
8.5. 
Concomitant Medications ...........................................................................................68 
8.6. 
Prohibited Medications or Procedures ........................................................................69 
8.6.1. 
Prohibited Medications .........................................................................................69 
8.6.2. 
Prohibited Procedures ...........................................................................................69 
8.7. 
Treatment Compliance ................................................................................................69 
9. 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT .............70 
9.1. 
Investigational Product ...............................................................................................70 
9.1.1. 
Pegcetacoplan .......................................................................................................70 
9.1.2. 
Placebo ..................................................................................................................70 

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9.2. 
Investigational Product Packaging and Labeling .......................................................70 
9.2.1. 
Packaging ..............................................................................................................70 
9.2.2. 
Labeling ................................................................................................................70 
9.3. 
Investigational Product Storage and Handling ...........................................................70 
9.4. 
Administration ............................................................................................................71 
9.5. 
Infusion Supplies ........................................................................................................72 
9.6. 
Investigational Product Accountability ......................................................................72 
9.7. 
Investigational Product Disposal ................................................................................72 
10. 
EFFICACY AND EXPLORATORY ASSESSMENTS ............................................73 
10.1. 
Efficacy Assessments .................................................................................................73 
10.1.1. 
Primary Efficacy Assessment .........................................................................73 
10.1.1.1. 
CAFS Scale ...............................................................................................73 
10.1.2. 
Secondary Efficacy Assessments .....................................................................73 
10.1.2.1. 
Slow Vital Capacity—Clinic ....................................................................74 
10.1.2.2. 
ALSAQ-40 ................................................................................................74 
10.1.2.3. 
Handheld Dynamometry ...........................................................................74 
10.2. 
Exploratory Assessments ............................................................................................74 
10.2.1. 
EQ-5D-5L........................................................................................................75 
10.2.2. 
Zarit Burden Interview .....................................................................................75 
10.2.3. 
Slow Vital Capacity—Home ............................................................................76 
10.2.4. 
Neurofilaments ...............................................................................................76 
10.2.5. 
Electrical Impedance Myography ...................................................................76 
11. 
SAFETY ASSESSMENTS ........................................................................................77 
11.1. 
Safety Parameters .......................................................................................................77 
11.1.1. 
Demographic/Medical History .......................................................................77 
11.1.2. 
Vital Signs ......................................................................................................77 
11.1.3. 
Electrocardiogram ...........................................................................................77 
11.1.4. 
Weight and Height ..........................................................................................77 
11.1.5. 
Physical Examination .....................................................................................78 
11.1.6. 
Injection/Infusion Site/Pump Safety Assessment ...........................................78 
11.1.7. 
C-SSRS ...........................................................................................................78 
11.1.8. 
Laboratory Assessments .................................................................................78 
11.1.8.1. 
Pregnancy Screen ......................................................................................81 

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11.1.9. 
Anti–Pegcetacoplan Peptide Antibody and Anti-PEG Antibody 
Assessments ....................................................................................................81 
11.1.10. 
Genetic Mutation(s) Results ...........................................................................81 
11.1.11. 
COVID-19 Assessment ..................................................................................82 
11.2. 
Adverse and Serious Adverse Events .........................................................................82 
11.2.1. 
Definitions ......................................................................................................82 
11.2.1.1. 
Adverse Events .........................................................................................82 
11.2.1.2. 
Unexpected Adverse Event .......................................................................82 
11.2.1.3. 
Serious Adverse Events ............................................................................82 
11.3. 
Relationship to Investigational Product ......................................................................83 
11.4. 
Severity of Events .......................................................................................................84 
11.5. 
Recording Adverse Events .........................................................................................84 
11.6. 
Reporting Adverse Events ..........................................................................................85 
11.7. 
Pregnancy ...................................................................................................................85 
11.7.1. 
Acceptable Methods of Contraception ...........................................................85 
11.8. 
Abuse, Misuse, Overdose, and Medication Error .......................................................86 
12. 
STATISTICS ..............................................................................................................87 
12.1. 
Determination of Sample Size ....................................................................................87 
12.2. 
Analysis Set ................................................................................................................87 
12.2.1. 
Screened Set ....................................................................................................87 
12.2.2. 
Safety Set ........................................................................................................87 
12.2.3. 
Intent-to-Treat Set ...........................................................................................87 
12.2.4. 
Modified Intent-to-Treat Set ...........................................................................88 
12.2.5. 
Per-Protocol Set ..............................................................................................88 
12.2.6. 
Pharmacokinetic Set .......................................................................................88 
12.2.7. 
Pharmacodynamic Set ....................................................................................88 
12.2.8. 
Data Review for Analysis Set .........................................................................88 
12.3. 
Efficacy Analysis ........................................................................................................88 
12.3.1. 
Analysis of Primary Efficacy Endpoint ..........................................................88 
12.3.2. 
Analysis of Secondary Efficacy Endpoints ....................................................89 
12.3.3. 
Analysis of Exploratory Efficacy Endpoints ..................................................90 
12.4. 
Safety Analysis ...........................................................................................................90 
12.5. 
Pharmacokinetic Analysis ..........................................................................................91 

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12.6. 
Pharmacodynamic Analysis........................................................................................91 
12.7. 
Other Analyses ............................................................................................................91 
12.8. 
Interim Analysis ..........................................................................................................91 
12.9. 
Data Monitoring Committee .......................................................................................91 
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................92 
13.1. 
Audits and Inspections ................................................................................................93 
13.2. 
Institutional Review Board/Independent Ethics Committee ......................................93 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................94 
15. 
ETHICS ......................................................................................................................95 
15.1. 
Ethics Review .............................................................................................................95 
15.2. 
Ethical Conduct of the Study ......................................................................................95 
15.3. 
Written Informed Consent ..........................................................................................95 
16. 
DATA HANDLING AND RECORDKEEPING .......................................................97 
16.1. 
Inspection of Records .................................................................................................97 
16.2. 
Retention of Records ..................................................................................................97 
17. 
PUBLICATION POLICY ..........................................................................................98 
18. 
LIST OF REFERENCES ............................................................................................99 
19. 
APPENDICES ..........................................................................................................102 
Appendix 1. 
Amendment History ......................................................................................103 
Appendix 2. 
Long-term Extension Phase ..........................................................................111 
 

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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................26 
Table 2: 
Schedule of Assessments—Randomized Treatment Period (Core) ...........................40 
Table 3: 
Schedule of Assessments—Open-Label (Pegcetacoplan) Treatment Period .............44 
Table 4: 
Laboratory Assessments .............................................................................................79 
Table 5: 
Blood Volumes Collected ...........................................................................................80 
Table 6: 
Definitions of Adverse Event Relatedness .................................................................83 
Table 7: 
Severity of Events .......................................................................................................84 
Table 8: 
Schedule of Assessments—Open-Label (Pegcetacoplan) Long-Term 
Extension Treatment Period .....................................................................................112 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................39 
 

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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist 
Term 
Explanation 
%SVC 
percentage of slow vital capacity 
ADA 
anti-drug antibodies 
AE 
adverse event 
AH50 
50% alternative hemolytic complement pathway activity 
AIHA 
autoimmune hemolytic anemia 
ALS 
amyotrophic lateral sclerosis 
ALSAQ-40 
Amyotrophic Lateral Sclerosis Assessment Questionnaire, 
40-item 
ALSFRS-R 
Revised Amyotrophic Lateral Sclerosis Functional Rating Scale 
aPTT 
activated partial thromboplastin time 
CAD 
cold agglutinin disease 
CAFS 
Combined Assessment of Function and Survival 
CH50 
50% classical hemolytic complement pathway activity 
CNS 
central nervous system 
CRF 
case report form 
C-SSRS 
Columbia Suicide Severity Rating Scale 
DPS 
diaphragm pacing system 
DMC 
data monitoring committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EIM 
electrical impedance myography 
EQ-5D-5L 
5-Level EuroQoL-5 Dimension 
ETFU 
early termination follow-up 
GA 
geographic atrophy 
GCP 
Good Clinical Practice 
HHD 
handheld dynamometry 
HRQoL 
health-related quality of life 

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Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist 
Term 
Explanation 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IRB 
institutional review board 
ITT 
intent-to-treat 
LDH 
lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
MN 
motor neuron 
NfL 
neurofilament light chain 
PCV13 
pneumococcal conjugate vaccine 13 
PD 
pharmacodynamic 
PEG 
polyethylene glycol  
PK 
pharmacokinetic(s) 
pNfH 
phosphorylated neurofilament heavy chain 
PP 
per-protocol 
PPSV23 
pneumococcal polysaccharide vaccine 23 
QTcF 
QT interval corrected using Fridericia’s method 
SAE 
serious adverse event 
sALS 
sporadic amyotrophic lateral sclerosis 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SVC 
slow vital capacity 
TEAE 
treatment-emergent adverse event 
WOCBP 
women of childbearing potential 
ZBI 
Zarit Burden Interview 
 

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4. 
INTRODUCTION 
This study is being conducted as part of a series of studies for the clinical development of 
pegcetacoplan (also known as APL-2). The study will be conducted in compliance with the 
protocol, Good Clinical Practice (GCP), and applicable regulatory requirements. The subject 
population will comprise of adult male and female subjects with sporadic amyotrophic lateral 
sclerosis (sALS). 
4.1. 
Amyotrophic Lateral Sclerosis and Unmet Medical Need 
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of unknown etiology 
for which there is no effective treatment. Progressive denervation of neuromuscular synapses in 
the peripheral nervous system and degeneration of upper and lower motor neurons in the central 
nervous system (CNS) result in muscle weakness, atrophy, paralysis, and ultimately death within 
2-3 years from the onset of symptoms. Initial presentation of ALS varies between affected 
individuals, and typically presents as spinal-onset disease (muscle weakness of the limbs), 
or bulbar-onset disease (difficulty with speech and swallowing). Sporadic ALS accounts for 90% 
of cases and has no clear etiology, while familial ALS accounts for 10% of cases and contains an 
underlying genetic component. However, while these 2 forms differ in causation, they appear 
pathologically and clinically indistinguishable. 
There is no known cure for ALS. There are 3 approved medications to treat ALS, riluzole, 
edaravone, and Relyvrio. Riluzole, approved in 1995 and available globally, is administered orally 
twice daily and delays time to tracheostomy or death in patients with ALS 
(Riluzole Package Insert 2016), prolonging survival by 2-3 months (Miller 2002). Edaravone, 
approved in the US in 2017, is administered in courses intravenously 
(Edaravone Package Insert 2017) and shows efficacy in only a small subset of patients with early 
ALS (Abe et al. 2017).  
Relyvrio (AMX0035), approved in the United States in 2022, is administered orally or via 
feeding tube twice daily and slows the loss of physical function in patients with ALS as 
measured by ALSFRS-R (Relyvrio Package Insert 2022).  
4.2. 
Information on the Investigational Product (Pegcetacoplan) 
Pegcetacoplan, the active ingredient in pegcetacoplan solution for subcutaneous infusion 
1080 mg/20 mL is a symmetrical molecule comprised of 2 pentadecapeptides covalently bound 
to the ends of a linear 40 kDa polyethylene glycol molecule. The peptide moieties bind to 
complement C3 and exert a broad inhibition of the complement cascade. The 40 kDa 
polyethylene glycol moiety imparts improved solubility and longer residence time in the body 
after administration of the drug product. 
Pegcetacoplan is provided as a solution in acetate buffer solution containing sorbitol for 
subcutaneous (SC) administration.  
Further details can be found in the current version of the pegcetacoplan Investigator’s Brochure (IB). 

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4.3. 
Study Rationale 
There is considerable evidence for the key role of neuroinflammation in ALS characterized by 
microglia activation, reactive astroglia, macrophage and lymphocyte infiltration, and 
overproduction of inflammatory cytokines, which correlate with motor neuron (MN) 
degeneration and disease progression (Chen et al. 2014; Murdock et al. 2017; 
Brettschneider et al. 2012; Turner et al. 2004; Ehrhart et al. 2015). Microglia maintain 
homeostasis by direct contact with the synaptic terminals and can respond to microenvironment 
signals and damage by removing defunct axon terminals (Kettenmann et al. 2013). During ALS 
progression, microglia transition from a protective phenotype to a proinflammatory and 
neurotoxic phenotype due to a proinflammatory stimuli, which results in synapse loss and the 
release of inflammatory factors that trigger the neurotoxic activity of astrocytes in the CNS 
(Liao et al. 2012; Chiu et al. 2013; Liddelow et al. 2017). Infiltrated muscle macrophages at the 
neuromuscular junction (NMJ) also result in denervation by phagocytizing presynaptic terminals 
(Wang et al. 2017). These neurotoxic mechanisms and interplays lead to self-destruction of MNs 
and, subsequently, the brain lose its ability to initiate and control the movement of muscles, 
including respiratory muscles. Uncontrolled inflammation is believed to drive, or actively 
participate, to disease progression. Therefore, therapy aimed at modulating the inflammatory and 
immune environment to preserve the remaining MNs may be beneficial in patients with ALS.  
The complement system is a pivotal component of both innate and adaptive immunity, 
contributing to immune surveillance, inflammation, and homeostasis (Kolev et al. 2014). 
Its 3 activation pathways (alternative, lectin and classical) converge to C3 and lead to its 
cleavage into its effectors, C3a and C3b, which in turn will lead to the formation of C5 
convertase and to C5 cleavage into C5a and C5b, and formation of the membrane attack 
complex. Overactivation of complement is a hallmark of many neurodegenerative diseases. 
Its diverse functions include C3a/C5a-triggered recruitment and activation of immune cells in 
particular microglia, macrophages, and lymphocytes, activation of glial cells by C3a/C3a 
receptor, C3b-mediated opsonization of neurons and synapse loss, and neuronal cell lysis by the 
membrane attack complex (Carpanini et al. 2019).  
Investigations in ALS animal models and patients with ALS demonstrate that complement-driven 
immune response may contribute to MN degeneration and progression of the disease. In animal 
model of ALS, disease progression significantly correlates with an upregulation of all complement 
effectors in muscles, peripheral nervous system, and spinal cord tissues, and an increased number of 
activated microglia/macrophages in the CNS and at the NMJ (Lee et al. 2018; Wang et al. 2017; 
Chiu et al. 2009). Inhibition of the complement downstream of C3 has been identified as a potential 
therapeutic target to slow disease progression in ALS in animal models (Lee et al. 2017). In patients 
or donors with ALS, high levels of complement C3 and downstream active fragments are present in 
blood, cerebral serum fluid, and in CNS tissues, in particular deposited on microglia and damaged 
neurites of the spinal cord and brain (Kawamata et al. 1992; Goldknopf et al. 2006; Sta et al. 2011; 
Ganesalingam et al. 2011; El Idrissi et al. 2016). The deposition of complement effectors, including 
C3/C3b, at the NMJ occurs early in the progression of ALS and precedes both motor end-plate 
denervation and degeneration of MNs (El Idrissi et al. 2016).  

Pe gcetac o pla n  
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C o nfi de ntial  
T he site of i nitiati o n of A L S is still u nclear. A m y otr o p hic lateral scl er osis was i nitiall y descri be d 
as a disease t h at ca us es t he pr o gressi ve l oss of M Ns i n t he C N S  f oll o we d b y a x o nal de ge n erati o n 
a n d m uscle atr o p h y. Gr o wi n g e vi de nce i n a ni mal m o dels a n d cli nical ne ur o p h ysi ol o g y s u p p ort a 
sec o n d h y p ot hesis i n w hic h M N pat h ol o g y ma y be gi n as a distal a x o n o pat h y a n d pr ocee d bac k t o 
t he C N S i n a “ d yi n g bac k” patter n (N ot o et al. 2 0 1 1 ; Fisc her et al. 2 0 0 4 ). Ot hers ha ve pr o p ose d 
a n i n de pe n de nt a n d ra n d o m de ge ner ati o n of u p per a n d l o wer M Ns ( Ra vits a n d La S pa da 2 0 0 9 ; 
va n de n B os et al. 2 0 1 9 ). W het her t he dis ease starts i n t he C N S or at t he N MJ, st o p pi n g t he 
i nfla m mati o n a n d i m m u ne res p o nse dri ve n b y c o m ple me nt s h o ul d de m o nstrate a p ositi ve effect 
o n disease pr o gr essi o n. Alt h o u g h pe gcetac o pla n d oes n ot cr oss t he bl o o d- brai n barri er, t here is 
gr o wi n g e vi de nce t hat t he bl o o d- brai n barrier is c o m pr o mise d i n patie nts wit h A L S 
(Gar b u z o va- Da vis a n d S a n ber g 2 0 1 4 ) a n d pe g cet ac o pla n ma y reac h t he brai n i n a d diti o n t o its 
p ote ntial be neficial i m pact o n i nfla m mati o n a n d p ha g oc yt osis at t he N MJ.  
St u dies of A L S pat h ol o g y ha ve i n v ol ve d all c o m ple me nt pat h wa ys a n d effect ors. Gi ve n t hat C 3 
is acti n g as a p oi nt of c o n ver ge nce of all acti vati o n pat h wa ys, e x erti n g direct effect or f u ncti o ns, 
a n d hel pi n g t o c o or di nate d o w nstrea m i m m u ne res p o nses, C 3 is a n attracti v e tar get t o treat A L S. 
Ta ke n t o get her, tar geti n g t he c o m ple me nt s yste m at t he le vel of C 3 usi n g pe gcetac o pla n ma y 
re vers e t he i m m u ne res p o nse, w hic h ma y st o p or sl o w d o w n A L S pr o gressi o n. 
4. 4.  
S u m m ar y of Cli nic al E x perie nce Wit h Pe gcet ac o pl a n  
Pe gcetac o pl a n is bei n g st u die d i n A L S a n d m ulti ple ot her c o m ple me nt- me diate d i n dicati o ns 
( par o x ys mal n oct ur n al he m o gl o bi n uria [ P N H], c ol d a g gl uti ni n disease [ C A D], 
c o m ple me nt - de pe n d e nt n e p hr o pat hies, a n d g e o gra p hic atr o p h y [ G A] sec o n dar y t o a ge-relat e d 
mac ular de g e nerati o n).  
T o date, pe gcetac o pl a n at d oses of ≥2 7 0 m g/ d a y a n d 1 0 8 0 m g t wice wee kl y ha ve bee n ge nerall y 
safe a n d well t olerate d w he n a d mi nistere d via S C i nf usi o n. N o e x pecte d s eri o us a d verse dr u g 
reacti o ns ha v e bee n i de ntifie d, a n d n o deat hs h a ve occ urre d t hat are c o nsi dere d rel ate d t o 
treat me nt wit h pe gcetac o pla n.  
St u d y A P L 2- 3 0 2, a ra n d o mize d, m ultice nter, o pe n- la bel, acti ve-c o m parat or, c o ntr olle d st u d y i n 
patie nts wit h P N H, de m o nstrate d t hat pe gcetac o pl a n 1 0 8 0 m g t wice wee kl y (a n d 1 0 8 0 m g e ver y 
t hir d da y d osi n g a dj ust me nt o pti o n) S C i nf usi o n pr o d uce d c o nsiste nt a n d m ea ni n gf ul effects o n 
rele va nt cli nical effi cac y meas ures wit h a fa v ora ble safet y pr ofile. Pe gcetac o pla n de m o nstrate d 
c o ntr ol of b ot h i ntra vasc ular a n d e xtr a vasc ul ar he m ol ysis b y i m pr o vi n g ke y he mat ol o gical 
ma nifestati o ns of P N H, r e d uci n g t he b ur de n of tra nsf usi o ns, a n d i m pr o vi n g patie nt-re p ort e d 
s y m pt o ms of fati g ue. Ta ke n t o get her, t hes e a nal yses pr o vi de str o n g e vi de n ce t hat treat me nt wit h 
pe gcetac o pla n pr o vi des a cli nicall y mea ni n gf ul a n d si g n ifica nt treat me nt be nefit i n t he treat me nt 
of P N H.  
St u d y 
 is a n on g oi n g  o pe n -la bel, pr os pecti ve, phase  2 st u d y ( Gertz  et al. 2 0 1 9 ) 
t hat i ncl u des s u bjects wit h war m a ut oi m m u ne he m ol ytic a ne mia ( w AI H A) a n d C A D t hat has 
c o m plete d t he i nitial Part A ( 3 3 6 da ys) a n d is c o nti n ui n g wit h Part B, t he l o n g -ter m e xte nsi o n p hase. 
Res ults fr o m Part A c o m prise d  2 4  s u bjects ( 1 2 dia g n ose d wit h w AI H A; 1 2 dia g n ose d wit h C A D) 
a n d i n dicate t hat pe gcetac o pla n is a ble t o ra pi dl y i ncrease he m o gl o bi n val ues wit hi n t he first wee ks 
of treat me nt a n d t his effect persiste d f or 4 8 wee ks. Res ults als o s h o we d i m pr o ve me nts i n he m ol ysis 
(s h o w n b y re d ucti o n of retic ul oc yte, lactate de h y dr o ge nase, a n d i n direct bilir u bi n). 
C CI

Pe gcetac o pla n  
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F urt her,  pe gcetac o pla n was ge nera ll y well t olerate d i n t his st u d y. S u bjects  i n t his st u d y are 
a d mi nistere d pe gcetac o pl a n s u bc uta ne o usl y at d os es of 2 7 0 m g/ da y or 3 6 0 m g/ da y.  
St u dies c o n d ucte d i n s u bjects wit h G A sec o n d ar y t o a ge-relate d mac ul ar de ge nerati o n  i ncl u de a 
p hase  2 st u d y (P O T- C P 1 2 1 6 1 4), a n d 2 phase 3 st u dies ( A P L 2 - 3 0 3 an d A P L 2- 3 0 4), as w ell as a 
l o n g-ter m e xte nsi o n st u d y 
. I n all of t hese st u dies t hat ha v e re p ort e d o utc o mes, 
u p t o 2 4 m o nt hs, pe gcetac o pla n a d mi nistere d i ntra vitreall y ( 1 5 m g) m o nt hl y or e ver y ot h er 
m o nt h was f o u n d t o be b ot h efficaci o us a n d ha d a t olera ble safet y pr ofile.   
Alt h o u g h t he a d mi nistrati o n r o ute of pe gcetac o pl a n i n patie nts wit h G A (i ntra vitre o us) is n ot t he 
o ne t hat will be use d t o tr eat patie nts wit h A L S (s u bc uta ne o us), t he m ec ha nis m b y w hic h 
c o m ple me nt C 3 a n d micr o glia c o o perat e t o eli mi nate t he tar g ete d cells (reti nal cells vers us m ot or 
ne ur o ns) is belie ve d t o b e si milar. 
Please ref er t o t he latest versi o n of t he pe g cetac o pla n I B f or m ore i nf or mati o n o n t he cli nical 
trials usi n g pe gcetac o pl a n.  
4. 4. 1.  
D ose R ati o n ale 
I n t his st u d y, pe gcetac o pl a n will be a d mi nistere d as a s u bc uta ne o us i nf usi o n at a d ose of 
1 0 8 0 m g t wice per w ee k. T he d ose selecti o n is base d o n pri or cli nical e x perie nce wit h 
pe gcetac o pla n. Re peate d S C d oses of 1 0 8 0 m g t wice per wee k h a ve b ee n a d mi nistere d t o healt h y 
s u bjects i n st u d y  
 f or 4 wee ks a n d a d ult s u bjects wit h P N H i n St u d y A P L 2- 3 0 2 f or at 
least 1 6 wee ks a n d were f o u n d t o be well t olerat e d i n b ot h st u dies. P har mac o d y na mic 
o bser vati o ns of s ustai ne d re d ucti o n of 5 0 % alter nati ve he m ol ytic c o m ple me nt pat h wa y acti vit y 
( A H 5 0) le v els a n d i ncr ease d C 3 le vels fr o m b ot h st u dies were c o nsiste nt wit h a c o ncl usi o n t hat 
pe gcetac o pla n i n hi bits alter nati ve c o m ple m e nt acti vit y. Statisticall y si g nifica nt i m pr o ve me nt i n 
efficac y bi o mar k er r es p o nse (e g, i ncr eas e i n he m o gl o bi n le vels) were o bs er ve d i n P N H s u bjects 
i n st u d y A P L 2-3 0 2 after treat me nt wit h pe gcetac o pla n. Pe gcetac o pla n is e x pecte d t o be 
p har mac ol o gicall y acti ve t o re g ulate ot her c o m ple me nt- dri ve n i m m u ne res p o nses i ncl u di n g 
t h ose t hat ma y c o ntri b ute t o M N de ge nerati o n a n d pr o gressi o n of t he diseas e i n s A L S patie nts. 
T he S C d oses of 1 0 8 0 m g t wice per w ee k of pe gcetac o pla n is dee me d t he a p pr o priate re gi me n 
f or t his cli nical trial t o treat a d ult male a n d fe mal e s u bjects wit h s A L S.  
Please ref er t o t he latest versi o n of t he pe g cetac o pla n I B f or t he o verall ris k/ be ne fit assess me nt 
a n d t he m ost acc urate a n d c urre nt i nf or mati o n re g ar di n g t he dr u g meta b olis m, p har mac o ki netics 
( P K), effi cac y, a n d saf et y of pe gcet ac o pla n. 
4. 5.  
Cli nic al Ris ks/ Be nefits of Pe gcet ac o pl a n  
Pe gcetac o pl a n has t he p ote ntial t o sl o w t he pr o gressi o n of A L S b y tar geti n g t he c o m ple me nt 
s yste m at t he le vel of C 3 a n d t h us pre ve nti n g t he d e ge nerati o n of m ot or ne ur o ns.  
T he safet y of s u bc uta ne o us pe gcetac o pla n a d mi nistrati o n has bee n st u die d i n m ulti ple p hase  2 a n d 3 
st u dies f or AI H A, C 3 gl o mer ul o ne p hr o pat hies, a n d P N H, wit h a n acce pta ble safet y pr ofile t o date. 
N o net heless, a n u m ber of safet y m o nit ori n g practices are bei n g e m pl o ye d b y t his pr ot oc ol t o e ns ure 
s u bject safet y, i ncl u di n g p h ysical e xa mi nati o n, vital si g ns m o nit ori n g, he mat ol o g y, ser u m c he mistr y, 
uri n al ysis, as well as pr o m pt re p orti n g of seri o us a d verse e ve nts ( S A Es).  
C CI
C CI

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Injection/infusion site/pump safety will be assessed during clinical visits when dosing coincides 
with clinic visit, and any significant finding from the assessment will be reported as an AE 
(see Section 11.2).  
Systemic complement inhibition might predispose individuals to infections caused by encapsulated 
organisms, including Streptococcus pneumoniae, Neisseria meningitidis (serogroups A, C, W, Y, 
and B), and Haemophilus influenzae type B. Subjects will be required to have documented evidence 
of vaccination against these organisms or agree to receive the vaccines (see Section 8.4). 
Administration of prophylactic antibiotic therapy chronically may be conducted, at the discretion of 
the treating investigator, in accordance with local treatment guidelines.  
Body temperature and vital signs will be monitored at all clinic visits, as well as relevant blood 
parameters throughout the study, to assess for signs of infection. Subjects will be provided with 
emergency study cards that include a list of symptoms associated with infections. This study card 
also guides subjects with instructions to contact their study physician or seek emergency medical 
care in the event they experience any of the listed symptoms. In the event of a suspected 
infection, the investigator should provide guidance on appropriate action to be taken. 
Systemic hypersensitivity reactions (eg, facial swelling, rash, urticaria) have occurred in patients 
treated with pegcetacoplan. One patient (less than 1% in clinical studies) experienced a serious 
allergic reaction which resolved after treatment with antihistamines. If a severe hypersensitivity 
reaction (including anaphylaxis) occurs, discontinue pegcetacoplan infusion immediately, institute 
appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved.  
The use of silica reagents in coagulation panels should be avoided. Apellis previously conducted 
an investigation into prolonged activated partial thromboplastin times (aPTTs) observed in 
subjects treated with pegcetacoplan. It was confirmed that false positive aPTT prolongation 
occurred when coagulation panels were performed using a Stago Analyzer and, specifically, 
silica reagents. It was determined that there was interference between the silica reagents and 
PEGylated pegcetacoplan, resulting in artificially prolonged aPTTs. 
Subjects should be instructed to take the investigational product (pegcetacoplan or placebo) 
as prescribed, and to contact the investigator immediately for guidance in the event of any 
missed doses. The sponsor’s medical monitor should be contacted before interrupting or 
discontinuing the investigational product. 
Apellis is not currently aware of any evidence associating pegcetacoplan use with specific risks or 
complications of COVID-19. Apellis recognizes the need to consider the public health risks of the 
COVID-19 pandemic within the context of conducting a clinical trial. Since these risks may change 
as the pandemic evolves, and may vary based on geographic location, Apellis will continue to 
evaluate the risk/benefit around study conduct on an ongoing and patient-by-patient basis. 
4.5.1. 
Safety Measures With Enrollment  
Because this is the first time pegcetacoplan is being studied in the ALS patient population, 
measurements are in place to closely monitor safety at the beginning of the study.  
Enrollment will be limited to a maximum of 20 subjects in the 4 weeks following first subject 
enrolled, and a maximum of 40 subjects during the first 8 weeks of the study. After the 8 weeks, 
enrollment will not be limited. 

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The data monitoring committee (DMC) will meet after 20 subjects have completed visit 3 
(week 4), and at regular intervals throughout the study as outlined in the DMC charter 
(see Section 12.9 for additional information).  
4.5.2. 
COVID-19 Risk Mitigation Measures 
In the event that an investigative site is closed, or subject is unable/unwilling to travel due to 
COVID-19, and, if in the opinion of the investigator it is in the subject’s best interest to continue 
in the study, the following mitigation measures may be implemented for the study and utilized if 
deemed necessary and authorized by the sponsor, including but not limited to:  
• In locations where home nursing services may be utilized, a home nursing vendor 
may be set up to complete assessments at a subject’s home. 
• Minimum safety assessments to be drawn at a certified local laboratory will be identified.  
• The electronic data capture (EDC) system will capture any missed assessments 
related to COVID-19. 
• Any change in COVID-19 status (serology or antigen), if available, will be 
captured separately in the EDC system. 
• Where applicable, relevant study documentation will be updated and communicated 
to health authorities and/or institutional review board (IRBs)/independent ethics 
committee (IECs) as required. 

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5. 
TRIAL OBJECTIVES AND ENDPOINTS 
5.1. 
Objectives 
5.1.1. 
Primary Objective 
The primary objective of this study is to assess the efficacy of twice per week SC doses of 
pegcetacoplan 1080 mg compared to placebo in subjects with sALS as measured by the 
Combined Assessment of Function and Survival (CAFS) rank score (joint-rank score). 
5.1.2. 
Secondary Objectives 
The following are the secondary objectives of this study: 
• To assess the effect of pegcetacoplan compared to placebo as measured by the 
Revised ALS Functional Rating scale (ALSFRS-R) score 
• To assess the effect of pegcetacoplan compared to placebo on disease progression as 
measured by respiratory function through percentage of slow vital capacity (%SVC) 
• To determine the effect of pegcetacoplan compared to placebo on muscle strength as 
measured by handheld dynamometry (HHD) 
• To determine the effect of pegcetacoplan compared to placebo on survival or 
specified state of disease progression 
• To assess the effect of pegcetacoplan compared to placebo on health-related quality 
of life (HRQoL) as measured by ALS Assessment Questionnaire (ALSAQ-40)  
• To assess the safety of pegcetacoplan during the randomized and open-label treatment 
periods through incidence and severity of TEAEs, clinical laboratory tests 
(hematology, chemistry), vital signs, and physical examinations 
• To assess the long-term efficacy of pegcetacoplan using ALSFRS-R, %SVC, HHD, 
and ALSAQ-40 during the open-label treatment period 
5.2. 
Endpoints 
5.2.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the difference in CAFS rank score (joint-rank score) at week 52. 
5.2.2. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are as follows: 
• Change from baseline in ALSFRS-R at week 52 
• Change from baseline in %SVC (at clinic visits) at week 52 
• Change from baseline in HHD megascore at week 52 
• Time to death, permanent tracheostomy, or permanent assisted ventilation up to week 52 
• Time to death up to week 52 

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• Change from baseline in ALSAQ-40 at week 52 
• Change from baseline of the randomized treatment period (visit 2) and of the open-label 
treatment period (visit 15) to week 104 for ALSFRS-R, %SVC, HHD, and ALSAQ-40 
• Time to death, permanent tracheostomy, or permanent assisted ventilation up to 
week 104 
• Time to death up to week 104 
5.2.3. 
Primary Safety Endpoints 
The primary safety endpoints are as follows: 
• Incidence and severity of TEAEs  
• Change from baseline in vital signs and clinical laboratory tests 
• Positive responses (Yes) to the Columbia Suicide Severity Rating Scale (C-SSRS) 
5.2.4. 
Exploratory Endpoints 
The exploratory endpoints are as follows: 
• Change from baseline in European Quality of Life–5 Dimensions–5 Level (EQ-5D-5L) 
at week 52, week 104, and week 156 
• Change from baseline in Zarit Burden Interview (ZBI) score at week 52, week 104, 
and week 156 
• Change from baseline of %SVC (home spirometry) at week 52 and week 104 
• Time to percutaneous endoscopic gastrostomy tube placement up to week 52, week 104, 
and week 156 
• Change from baseline in serum neurofilament light chain (NfL) at week 52, week 104, 
and week 156 
• Change from baseline in serum phosphorylated neurofilament heavy chain (pNfH) at 
week 52, week 104, and week 156 
• Change from baseline in electrical impedance myography (EIM) at week 52, week 104, 
and week 156 (only at select investigational sites chosen to complete this) 
• Pegcetacoplan PK concentrations at week 52, week 104, and week 156 
• Changes from baseline at week 52, week 104, and week 156 in complement biomarkers: 
− Classical hemolytic complement pathway activity (CH50) 
− AH50 
− C3 levels 
• Immunogenicity: presence of antibodies to PEG moiety and peptide moiety of 
pegcetacoplan during the randomized and open-label treatment periods 

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• Change from baseline of the randomized treatment period (week 1) and of the open-label 
treatment period (week 52) to week 156 for ALSFRS-R, %SVC (in-clinic), HHD, 
and ALSAQ-40 
• Time to death, permanent tracheostomy, or permanent assisted ventilation up to 
week 156 
• Time to death up to week 156 
 

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6. 
INVESTIGATIONAL PLAN 
See Figure 1 for the study design, Table 2 for the schedule of assessments for the randomized 
treatment period, and Table 3 for the schedule of assessments for the open-label (pegcetacoplan) 
treatment period; Table 8 for the schedule of assessments for the open-label (pegcetacoplan) 
long-term extension treatment period. 
6.1. 
Overall Study Design 
This is a phase 2, randomized, double-blind, placebo-controlled, multicenter, efficacy and safety 
study of SC pegcetacoplan 1080 mg twice per week conducted in approximately 228 subjects 
with ALS. The study has been designed to minimize the burden on subjects with use of at-home 
assessments and limited number of clinic visits. 
The planned length of participation in the study for each subject is a maximum of approximately 
168 weeks. This study will consist of 5 parts: 
• Part 1: Up to 6-week screening period 
• Part 2: 52-week randomized treatment period 
• Part 3: 52-week open-label (pegcetacoplan) treatment period 
• Part 4: 52-week open-label (pegcetacoplan) long-term extension treatment period 
• Part 5: 6-week off-treatment follow-up period 
Throughout this protocol, “investigational product” refers to the blinded treatment, whether that 
is pegcetacoplan or placebo.  
6.1.1. 
Part 1: Screening Period (Up to 6 Weeks) 
• Informed consent will be obtained at screening prior to any study-related procedures 
being conducted. 
• Subjects (and/or caregivers) will be trained on the use of at-home assessments. 
6.1.2. 
Part 2: Randomized Treatment Period (52 Weeks) 
Approximately 228 subjects who meet all of the inclusion criteria and none of the exclusion 
criteria will be randomized 2:1 to either the pegcetacoplan treatment group or the placebo group. 
Safety and efficacy will be assessed and will include once per week at-home measurements, 
monthly calls, and clinic visits. Subjects who discontinue treatment early and do not complete 
Part 2 will continue to Part 5. 
6.1.2.1. 
Pegcetacoplan Treatment Group 
• Subjects randomized to pegcetacoplan will receive SC pegcetacoplan 1080 mg twice 
per week for 52 weeks.  
6.1.2.2. 
Placebo Treatment Group 
• Subjects randomized to placebo will receive SC placebo twice per week for 52 weeks. 

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6.1.3. 
Part 3: Open-Label (Pegcetacoplan) Treatment Period (52 Weeks) 
At the end of Part 2, all subjects from both treatment groups will continue to Part 3. All subjects 
participating in Part 3 will be treated with pegcetacoplan 1080 mg twice per week up to 
week 104. Subjects who complete Part 3, will enter Part 4. Subjects who do not continue to 
Part 3, or who have started Part 3 but discontinue treatment early, will continue to Part 5. 
6.1.4. 
Part 4: Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period 
(52 Weeks) 
At the end of Part 3, any subject who, in the opinion of the investigator, is experiencing clinical 
benefit from pegcetacoplan administration will be invited to continue to Part 4, the open-label 
long-term extension treatment period. All subjects participating in Part 4 will be treated with 
pegcetacoplan 1080 mg twice per week up to week 156. Subjects who complete Part 4 will enter 
Part 5. Subjects who do not continue to Part 4, or who have started Part 4 but discontinue 
treatment early, will continue to Part 5. 
6.1.5. 
Part 5: Off-Treatment Follow-up Period (6 Weeks) 
During Part 5, all subjects who have discontinued the investigational product (blinded 
pegcetacoplan/placebo or open-label pegcetacoplan) will complete a follow-up visit 6 weeks later.  
6.2. 
Number of Subjects 
There will be approximately 228 subjects diagnosed with sALS enrolled in the study. 
6.3. 
Treatment Assignment 
All subjects who meet all the inclusion criteria and none of the exclusion criteria will be enrolled 
in the study, until such time that approximately 228 subjects have been enrolled in the study. 
At the first visit of Part 2, subjects will be randomized after confirmation of study eligibility in a 
ratio of 2:1 via a computer-generated randomization schedule to receive pegcetacoplan or 
placebo. The randomization will be performed centrally and stratified by location of first muscle 
weakness (limb or bulbar) and riluzole and edaravone use. The stratification by location of onset 
and riluzole use will ensure balance between treatment groups for the respective stratification 
factors. Fixed block randomization will be used to ensure that approximately equals number of 
subjects are assigned each treatment within strata.  
6.4. 
Criteria for Study Termination 
The sponsor reserves the right to suspend or discontinue this study for administrative and/or 
safety reasons, at any time. The investigator reserves the right to discontinue dosing subjects, 
at any time, for safety reasons. 
 

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Figure 1: 
Study Design 
 
 
Abbreviations: ALSFRS-R = Revised Amyotrophic Lateral Sclerosis Functional Rating Scale; EQ-5D-5L = European Quality of Life–5 Dimensions–5 Level; 
W = week(s); ZBI = Zarit Burden Interview. 
Notes: The initial baseline (visit 2b) spirometry assessments will be conducted in the clinic; every subsequent spirometry assessment will be conducted at home. 
ALSFRS-R questionnaire will be administered via the phone, including at screening. 
 
 
 
 
 
 
  
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 

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g Zarit Burden Interview will be administered to the same caregiver throughout the subject’s study participation. If subject is not actively being assisted by a caregiver at baseline, 
ZBI will be administered to the subject’s anticipated caregiver. If subject does not have an anticipated caregiver/relative at baseline, ZBI administration will begin when/if the 
subject starts requiring a caregiver. Please see Section 10.2.2 for the definition of a caregiver. 
h At investigational sites selected to conduct EIM, EIM will occur before HHD. 
i Blood pregnancy assessment and urine pregnancy test will be completed for WOCBP at the scheduled time points indicated. 
j Blood samples will be taken after vital signs and 12-lead ECG have been completed. 
k Additional samples for anti–pegcetacoplan peptide antibody and anti-PEG antibody will be collected every 6 months from last dose until it can be determined that the subject’s 
antibody levels are at baseline or that further testing is not needed. 
l At baseline visit 2b, in addition to the at-clinic %SVC using the clinic spirometer, subjects will also complete %SVC using their at-home devices. Training for the at-home SVC 
assessments will occur at baseline visit 2b after completion of the assessments using the at-home devices. Research personnel will provide training to the subject (and/or 
caregiver) until the subject (and/or caregiver) is able to perform the assessments independently. Only subjects (and/or caregivers) trained to perform the at-home assessments 
will be allowed to continue in the study.  
m At-home %SVC will occur on a dosing day each week. 
n Subjects (or caregiver) will administer SC pegcetacoplan, after receiving appropriate training by a nurse or other research personnel. The research personnel providing training 
will be made available for a minimum of 6 days on treatment (2 doses) to ensure the subject (or caregiver) has been trained to conduct self-administration; the duration can be 
shortened if ability to self-administer happens sooner. During training, the subject (or caregiver) must demonstrate to the research personnel his/her ability to safely and 
effectively administer study drug using the infusion pump. Following self-administration training, subject (or caregiver) may self-administer the SC infusions without 
supervision on all dosing days.  
o Between clinic visits, subjects will be instructed to report any injection site reaction and/or any other AEs to the study coordinator.  
p Investigational product dispensation for home administration may occur at different times throughout the study.  
q Baseline is divided into visit 2a and visit 2b so questionnaires can be completed at the subject’s home prior to dosing.  
a.  
Visit 2a will be conducted at home via the telephone one day prior to visit 2b.  
b. 
Visit 2b will be conducted at clinic; please confirm completion of visit 2a assessments before starting visit 2b assessments. 
r Only subjects not enrolling in Part 3 will return unused investigational product. 
s Visit 15b is only applicable for subjects who do not enter Part 3. 
t Subjects who discontinue early should complete an early termination follow-up visit 6 weeks (±7 days) after treatment discontinuation. 
u At-home measurements will be performed once per week on a dosing day through the last clinic visit.  
 

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e Zarit Burden Interview will be administered to the same caregiver throughout the subject’s study participation. If subject is not actively being assisted by a caregiver at baseline, 
ZBI will be administered to the subject’s anticipated caregiver. If subject does not have an anticipated caregiver/relative at baseline, ZBI administration will begin when/if the 
subject starts requiring a caregiver. Please see Section 10.2.2 for the definition of a caregiver. 
f At investigational sites selected to conduct EIM, EIM will occur before HHD. 
g Urine pregnancy test will be completed for WOCBP.  
h Blood samples will be taken after vital signs and 12-lead ECG have been completed.  
i Additional samples for anti–pegcetacoplan peptide antibody and anti-PEG antibody will be collected every 6 months from last dose until it can be determined that the subject’s 
antibody levels are at baseline or that further testing is not needed. 
j At-home %SVC will occur on a dosing day each week. 
k Subjects (or caregiver) will administer SC pegcetacoplan, after receiving appropriate training by a nurse or other research personnel.  
l Between clinic visits, subjects will be instructed to report any injection site reaction and/or any other AEs to the study coordinator. 
m Investigational product dispensation for home administration may occur at different times throughout the study. At weeks 64 and 88, which are between clinic visits, subjects or 
their caregiver(s) may be required to come into the clinic to pick-up additional IP and supplies. Depending on the length of time between the week 88 additional IP pick-up visit 
and the week 104 clinic visit, an unscheduled dispensation visit for pick-up of IP and/or supplies may be necessary. 
n Subjects who discontinue early should complete an early termination follow-up visit 6 weeks (± 7 days) after treatment discontinuation. 
o At-home measurements will be performed once per week, on the same day as when subject was receiving treatment, through the last clinic visit.  
p Only subjects not enrolling in Part 4 will return unused investigational product. 

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6.5. 
End of Trial Definition 
A participant is considered to have completed the study if he/she has completed all parts of the 
study including the last scheduled procedure shown in Table 8, Schedule of Assessments–
Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period. The end of the study is 
defined as the date of the last scheduled procedure shown in the schedule of assessments for the 
last participant in the trial globally. 
6.6. 
Study Procedures 
Please see the schedule of assessments (Table 2, Table 3, and Table 8) for a summary of the 
schedule of study participation and procedures. The schedule of visit dates for Part 2, 
randomized treatment period, and Part 3, open-label (pegcetacoplan) treatment period should be 
established, either prior to or at the time of screening, allowing subjects an opportunity to assess 
whether there are likely to be significant conflicts with other activities or planned absences. 
6.6.1. 
Screening Period: Visit 1 
The subject will be screened to confirm that the subject-selection criteria for the study has been met. 
Informed consent will be obtained at screening prior to any study-related procedures being 
conducted.  
During the screening period (from week -6 to baseline), pulmonary function tests (slow vital 
capacity [SVC]) and clinical laboratory tests (eg, hematology, coagulation, serum chemistry, 
urinalysis) may be repeated once with written approval from the sponsor (including the assigned 
medical monitor), with no requirement to designate the subject as a screen failure, unless the 
subject fails the second time. Subjects who do not meet screening SVC of ≥60% or clinical 
laboratory-related screening criteria may still qualify for study entry without having to complete 
the full rescreening process as long as the %SVC and all clinical laboratory-related values meet 
the criteria for study entry within the screening period.  
With the exception of %SVC and clinical laboratory-related entry criteria, subjects who have 
given informed consent and fail to meet at least 1 of the inclusion and/or exclusion criteria and 
have not been randomized or administered investigational product(s) will be designated as a 
screen failure. Any subject designated as a screen failure may only be rescreened once with 
written approval from the sponsor and will be required to recomplete the full screening process. 
Any %SVC or clinical laboratory test that is reconducted to confirm eligibility must be 
conducted within the screening period after written approval from the sponsor/medical monitor 
has been received, or the subject will be designated as a screen failure.  
At the screening visit, the following assessments will be performed: 
Note: 12-lead electrocardiogram (ECG) and vital sign measurements must be performed prior to 
blood sampling.  
• Informed consent 
• Demographics 
• Medical and treatment history 

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• Inclusion and exclusion criteria, including 
− ALSFRS-R via the telephone at clinic 
− %SVC using clinic spirometer 
− C-SSRS 
• Concomitant medications  
• Vaccination history (see Section 8.4), administration of required vaccination(s) 
• Physical examination 
• Weight and height 
• Vital sign measurements (prior to blood sampling) 
• 12-lead ECG (prior to blood sampling) 
• Urinalysis 
• Blood (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pregnancy (β–human chorionic gonadotropin and follicle-stimulating hormone) 
for women of childbearing potential (WOCBP) 
− Hepatitis C virus, hepatitis B surface antigen 
• Assess subject’s (or caregiver’s) ability to perform SVC measurements using the at-home 
devices. Subjects will not take home any of these devices from the screening visit. 
Subjects missing documented evidence of any of the required vaccinations (within 5 years of 
baseline visit 2b) must receive the vaccinations at least 7 days prior to baseline visit 2b 
(see Section 8.4.1).  
6.6.2. 
Baseline: Visit 2a and Visit 2b 
6.6.2.1. 
Baseline: Visit 2a 
At the baseline visit 2a, the following assessments will be performed at home: 
• Questionnaires via the telephone: 
− ALSFRS-R 
− EQ-5D-5L  
− ZBI  

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6.6.2.2. 
Baseline: Visit 2b 
At the baseline visit 2b, the following assessments will be performed at clinic: 
Note: 12-lead ECG and vital sign measurements must be performed prior to blood sampling, 
EIM must be performed prior to HHD (if applicable). All assessments must be performed prior 
to dosing (with the exception of injection site assessments, adverse reaction review, and postdose 
vital sign measurements)  
• Confirmation of inclusion and exclusion criteria  
• Confirm age at time of visit 2b 
• Concomitant medications  
• Vaccination history (see Section 8.4) 
• Physical Examination 
• Weight 
• Predose vital sign measurements (prior to blood sampling and dosing)  
• 12-lead ECG (prior to blood sampling and dosing) 
• Questionnaires: 
− ALSAQ-40 
− C-SSRS 
• %SVC using clinic spirometer  
• %SVC using at-home spirometer 
• Training on at-home assessments 
• EIM (only at select investigational sites) (prior to HHD) 
• HHD (after EIM, if applicable) 
• Urinalysis 
• Urine pregnancy test for WOCBP 
• Blood (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pharmacokinetics 
− Anti–pegcetacoplan peptide antibody and anti-PEG antibody assays 
− Complement profile (C3, CH50, and AH50) 
− NfL 
− pNfH 

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• Investigational product administration: baseline dosing will be administered at the 
clinic by a nurse. 
− Injection site assessment 
− Adverse events review 
− Postdose vital sign measurements 
At the visit, subjects will receive the at-home devices. Trained research personnel will train the 
subject (and/or caregiver) to perform both the administration of pegcetacoplan and the at-home 
assessments independently. Only subjects/caregivers who have been trained to self-administer 
pegcetacoplan and the at-home assessments will be able to continue in the study. If subjects 
require caregiver assistance in administering pegcetacoplan and the at-home assessments, 
the caregiver must continue assisting in the administration of at-home assessments for the 
duration of study participation.  
(Note: throughout this protocol, the term “self-administration” refers to administration of the 
at-home assessments/investigational product by either a trained subject or trained caregiver). 
6.6.3. 
Randomized Treatment Period (Core) Visits 
Part 2 (randomized treatment period) of this study is composed of 4 different types of visits: 
• Clinic visits (Section 6.6.3.1)  
• Home visits (Section 6.6.3.2) 
• Telephone visits (Section 6.6.3.3) 
• Follow-up (core) visit (Section 6.6.3.4)  
6.6.3.1. 
Randomized Treatment Period (Core)—Clinic Visits: Visits 3, 5, 8, 11, 15 
In the randomized treatment period, prior to the clinic visits, the following should be assessed on 
a dosing day, at home, within visit window before the day of the clinic visit: 
• Questionnaires via the telephone: 
− ALSFRS-R 
− EQ-5D-5L  
− ZBI 
At the clinic visits, the following assessments will be performed: 
Note: 12-lead ECG and vital sign measurements must be performed prior to blood sampling, 
EIM must be performed prior to HHD (if applicable). If clinic visit coincides with a dosing day, 
all assessments must be performed prior to dosing (with the exception of injection site 
assessments and adverse reaction review).  
• Concomitant medications 
• Weight 
• Vital sign measurements (prior to blood sampling) 

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• 12-lead ECG (prior to blood sampling) 
• Questionnaires: 
− ALSAQ-40 
− C-SSRS 
• %SVC using clinic spirometer 
• EIM (only at select investigational sites) (prior to HHD) 
• HHD (after EIM, if applicable) 
• Urinalysis 
• Urine pregnancy test for WOCBP 
• Blood sample (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pharmacokinetics 
− Anti–pegcetacoplan peptide antibody and anti-PEG antibody assays 
− Complement profile (C3, CH50, and AH50) 
− NfL 
− pNfH 
• Investigational product administration (if applicable) 
• Injection site assessment (if applicable) 
• AEs review 
• Return of unused investigational product (only at visit 15 for subjects not enrolling in 
Part 3) 
After visit 15, subjects will enroll in Part 3, the open-label (pegcetacoplan) treatment period. 
If the subject chooses not to participate in Part 3, they will complete the follow-up (core) visit 
(Study visit 15b), 6 weeks after visit 15.  
6.6.3.2. 
Randomized Treatment Period (Core)—Home Assessments  
During the randomized treatment period, on days when there are no clinic or telephone visits, 
the following assessments will be performed at the subject’s home beginning after baseline:  
• Twice per week: 
− Investigational product administration. Subjects and/or caregivers will be trained 
by research personnel before subject/caregiver can self-administer 
(see Section 9.4). Subjects should not deviate from their dosing schedule: Day 1 
and Day 4 of each treatment week (eg, Tuesday/Friday/Tuesday). 

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• Once per week on a dosing day:  
− %SVC with handheld spirometry (self-administration) 
• Throughout the randomized treatment period: 
− Self-reported injection site assessment 
− AEs review  
6.6.3.3. 
Randomized Treatment Period (Core)—Telephone Visits: Visits 4T, 6-7T, 
9-10T, 12-14T 
At telephone visits in the randomized treatment period, the following assessments will be 
performed on a dosing day:  
• Questionnaires via the telephone: 
− ALSFRS-R  
− EQ-5D-5L  
− ZBI  
• Self-reported injection site assessment  
• AEs review 
• Urine pregnancy test for WOCBP (only at visit 13T) 
6.6.3.4. 
Follow-Up (Core) Visit: Visit 15b 
If the subject chooses not to participate in Part 3, they will complete the follow-up (core) visit, 
6 weeks after visit 15.  
Prior to the follow-up (core) visit, the following should be assessed, at home, within visit 
window before the day of the follow-up (core) visit: 
• Questionnaires: 
− ALSFRS-R 
− EQ-5D-5L  
− ZBI  
At the follow-up (core) visit, the following assessments will be performed: 
Note: 12-lead ECG and vital sign measurements must be performed prior to blood sampling, 
EIM must be performed prior to HHD (if applicable).  
• Concomitant medications 
• Physical examination 
• Weight  
• Vital sign measurements (prior to blood sampling) 

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• 12-lead ECG (prior to blood sampling) 
• Questionnaires: 
− ALSAQ-40 
− C-SSRS 
• %SVC using clinic spirometer 
• EIM (only at select investigational sites) (prior to HHD) 
• HHD (after EIM, if applicable) 
• Urinalysis 
• Urine pregnancy test for WOCBP 
• Blood sample (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pharmacokinetics 
− Anti–pegcetacoplan peptide antibody and anti-PEG antibody assays 
− Complement profile (C3, CH50, and AH50) 
− NfL 
− pNfH 
• AEs review  
• Return of at-home devices 
6.6.4. 
Open-Label (Pegcetacoplan) Treatment Period Visits 
Part 3 (open-label [pegcetacoplan] treatment period) of this study is composed of 4 different 
types of visits: 
• Clinic visits (Section 6.6.4.1) 
• Home assessments (Section 6.6.4.2) 
• Telephone visits (Section 6.6.4.3) 
• Follow-up (open-label) visit (Section 6.6.4.4) 
6.6.4.1. 
Open-Label (Pegcetacoplan) Treatment Period—Clinic Visits: Visits 16, 21, 28 
In the open-label (pegcetacoplan) treatment period, prior to the clinic visits, the following should 
be assessed on a dosing day, at home, within visit window before the day of the clinic visit: 
• Questionnaires via the telephone: 
− ALSFRS-R  
− EQ-5D-5L  
− ZBI 

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At the clinic visits, the following assessments will be performed:  
Note: 12-lead ECG and vital sign measurements must be performed prior to blood sampling, 
EIM must be performed prior to HHD (if applicable). If clinic visit coincides with a dosing day, 
all assessments must be performed prior to dosing (with the exception of injection site 
assessments and adverse reaction review).  
• Concomitant medications 
• Weight  
• Vital sign measurements (prior to blood sampling) 
• 12-lead ECG (prior to blood sampling) 
• Questionnaires: 
− ALSAQ-40 
− C-SSRS 
• %SVC using clinic spirometer 
• EIM (only at select investigational sites) (prior to HHD) 
• HHD (after EIM, if applicable) 
• Urinalysis 
• Urine pregnancy test for WOCBP 
• Blood sample (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pharmacokinetics 
− Anti–pegcetacoplan peptide antibody and anti-PEG antibody assays 
− Complement profile (C3, CH50, and AH50) 
− NfL 
− pNfH 
• Investigational product administration (if applicable) 
• Injection site assessment (if applicable) 
• AEs review 
• Return of unused investigational product (only at visit 28) 

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6.6.4.2. 
Open-Label (Pegcetacoplan) Treatment Period—Home Assessments 
During the open-label (pegcetacoplan) treatment period, on days when there are no clinic or 
telephone visits, the following assessments will be performed at home:  
• Twice per week: 
− Pegcetacoplan administration. Subjects and/or caregivers will be trained by a 
nurse or other research personnel before subject can self-administer 
(see Section 9.4). Subjects should not deviate from their dosing schedule: day 1 and 
day 4 of each treatment week (eg, Tuesday/Friday/Tuesday). 
• Once per week on a dosing day:  
− %SVC with handheld spirometry (self-administration) 
• Throughout the open-label period: 
− Self-reported injection site assessment 
− AEs review 
6.6.4.3. 
Open-Label (Pegcetacoplan) Treatment Period—Telephone Visits: 
Visits 17T-20T, 22T-27T 
At telephone visits in the open-label (pegcetacoplan) treatment period, the following assessments 
will be performed on a dosing day: 
• Questionnaires via the telephone: 
− ALSFRS-R  
− EQ-5D-5L 
− ZBI  
• Self-reported injection site assessment 
• AEs review 
• Urine pregnancy test for WOCBP (only at visits 18T, 24T, and 26T) 
6.6.4.4. 
Open-Label (Pegcetacoplan) Treatment Period—Follow-up Visit: Visit 28b 
Prior to the follow-up (open-label) visit, the following should be assessed, at home, within visit 
window before the day of the follow-up (open-label) visit: 
• Questionnaires via the telephone: 
− ALSFRS-R  
− EQ-5D-5L  
− ZBI 

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At the follow-up (open-label) visit, the following assessments will be performed: 
Note: 12-lead ECG and vital sign measurements must be performed prior to blood sampling, 
EIM must be performed prior to HHD (if applicable).  
• Concomitant medications 
• Physical examination 
• Weight  
• Vital sign measurements (prior to blood sampling) 
• 12-lead ECG (prior to blood sampling) 
• Questionnaires: 
− ALSAQ-40 
− C-SSRS 
• %SVC using clinic spirometer 
• EIM (only at select investigational sites) (prior to HHD) 
• HHD (after EIM, if applicable) 
• Urinalysis 
• Urine pregnancy test for WOCBP 
• Blood sample (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pharmacokinetics 
− Anti–pegcetacoplan peptide antibody and anti-PEG antibody assays 
− Complement profile (C3, CH50, and AH50) 
− NfL 
− pNfH 
• AEs review  
• Return of at-home devices 
6.6.5. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period 
Part 4 (open-label [pegcetacoplan] long-term extension period) of this study is composed of 
4 different types of visits: 
• Clinic visits (Section 6.6.5.1) 
• Home assessments (Section 6.6.5.2) 
• Telephone visits (Section 6.6.5.3) 
• Follow-up (open-label) visit (Section 6.6.5.4) 

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6.6.5.1. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period—Clinic 
Visits: Visits 31, 36, 41 
In the open-label (pegcetacoplan) long-term extension treatment period, prior to the clinic visits, 
the following should be assessed on a dosing day, at home, within visit window before the day of 
the clinic visit: 
• Questionnaires via the telephone: 
− ALSFRS-R  
− EQ-5D-5L  
− ZBI 
At the clinic visits, the following assessments will be performed:  
Note: 12-lead ECG and vital sign measurements must be performed prior to blood sampling, 
EIM must be performed prior to HHD (if applicable). If clinic visit coincides with a dosing day, 
all assessments must be performed prior to dosing (with the exception of injection site 
assessments and adverse reaction review).  
• Concomitant medications 
• Weight  
• Vital sign measurements (prior to blood sampling) 
• 12-lead ECG (prior to blood sampling) 
• Questionnaires: 
− ALSAQ-40 
− C-SSRS 
• %SVC using clinic spirometer 
• EIM (only at select investigational sites) (prior to HHD) 
• HHD (after EIM, if applicable) 
• Urinalysis 
• Urine pregnancy test for WOCBP 
• Blood sample (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pharmacokinetics 
− Anti–pegcetacoplan peptide antibody and anti-PEG antibody assays 
− Complement profile (C3, CH50, and AH50) 
− NfL 
− pNfH 

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• Investigational product administration (if applicable) 
• Injection site assessment (if applicable) 
• AEs review 
• Return of unused investigational product (only at visit 41) 
6.6.5.2. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period—Home 
Assessments 
During the open-label (pegcetacoplan) long-term extension treatment period, on days when there 
are no clinic or telephone visits, the following assessments will be performed at home:  
• Twice per week: 
− Pegcetacoplan administration. Subjects and/or caregivers will be trained by a 
nurse or other research personnel before subject can self-administer 
(see Section 9.4). Subjects should not deviate from their dosing schedule: day 1 
and day 4 of each treatment week (eg, Tuesday/Friday/Tuesday). 
• Throughout the open-label period: 
− Self-reported injection site assessment 
− AEs review 
6.6.5.3. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period—
Telephone Visits: Visits 29T, 30T, 32T-35T, 37T-40T 
At telephone visits in the open-label (pegcetacoplan) long-term extension treatment period, 
the following assessments will be performed on a dosing day: 
• Questionnaires via the telephone: 
− ALSFRS-R  
• Self-reported injection site assessment 
• AEs review 
• Urine pregnancy test for WOCBP (only at Visits 34T and 39T) 
6.6.5.4. 
Open-Label (Pegcetacoplan) Long-Term Extension Treatment Period—
Follow-up Visit: Visit 41b 
Prior to the follow-up (open-label, long-term extension) visit, the following should be assessed, 
at home, within visit window before the day of the follow-up (open-label) visit: 
• Questionnaires via the telephone: 
− ALSFRS-R  
− EQ-5D-5L  
− ZBI  

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At the follow-up (open-label) visit, the following assessments will be performed: 
Note: 12-lead ECG and vital sign measurements must be performed prior to blood sampling, 
EIM must be performed prior to HHD (if applicable).  
• Concomitant medications 
• Physical examination 
• Weight  
• Vital sign measurements (prior to blood sampling) 
• 12-lead ECG (prior to blood sampling) 
• Questionnaires: 
− ALSAQ-40 
− C-SSRS 
• %SVC using clinic spirometer 
• EIM (only at select investigational sites) (prior to HHD) 
• HHD (after EIM, if applicable) 
• Urinalysis 
• Urine pregnancy test for WOCBP 
• Blood sample (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pharmacokinetics 
− Anti–pegcetacoplan peptide antibody and anti-PEG antibody assays 
− Complement profile (C3, CH50, and AH50) 
− NfL 
− pNfH 
• AEs review  
• Return of at-home devices 
6.6.6. 
Early Termination Follow-Up Visit 
Subjects who discontinue prior to the follow-up (core)/follow-up (open-label)/follow-up (open-label, 
long-term extension) visit will complete an early termination follow-up visit 6 weeks (±7 days) after 
their last dose of the investigational product.  
Prior to the early termination follow-up visit, the following will be assessed, at home, within visit 
window before the day of the early termination follow-up visit: 

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• Questionnaires via the telephone: 
− ALSFRS-R 
− EQ-5D-5L 
− ZBI 
At the early termination follow-up visit, the following assessments will be performed: 
Note: 12-lead ECG and vital sign measurements must be performed prior to blood sampling, 
and EIM must be performed prior to HHD (if applicable).  
• Concomitant medications 
• Physical examination 
• Weight  
• Vital sign measurements (prior to blood sampling) 
• 12-lead ECG (prior to blood sampling) 
• Questionnaires: 
− ALSAQ-40 
− C-SSRS 
• %SVC using clinic spirometer 
• EIM (only at select investigational sites) (prior to HHD) 
• HHD (after EIM, if applicable) 
• Urinalysis 
• Urine pregnancy test for WOCBP 
• Blood sample (after vital sign measurements and 12-lead ECG) 
− Hematology 
− Chemistry 
− Pharmacokinetics 
− Anti–pegcetacoplan peptide antibody and anti-PEG antibody assays 
− Complement profile (C3, CH50, and AH50) 
− NfL 
− pNfH 
• AEs review 
• Return of at-home devices 

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6.6.7. 
Unscheduled Visit(s) 
Subjects may be asked to return to the clinic for additional visits if considered necessary by the 
investigator. Unscheduled visits may include (but are not limited to) any of the procedures listed 
in the schedule of assessments (see Table 2, Table 3, and Table 8). 

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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Subject Inclusion Criteria 
1. Sporadic ALS diagnosed as definite, probable, or laboratory-supported probable as 
defined by the revised El Escorial criteria (Brooks et al. 2000) 
2. At least 18 years of age 
3. SVC ≥60% of the predicted value based on age, sex, and height at screening 
4. Onset of ALS symptoms within 72 weeks prior to screening 
5. Total ALSFRS-R score of ≥30 at screening 
6. WOCBP, defined as any woman who has experienced menarche and who is NOT 
permanently sterile or postmenopausal  
a. must have a negative pregnancy test at screening and  
b. must agree to use protocol defined methods of contraception for the duration of the 
study and 90 days after their last dose of the investigational product 
− Postmenopausal is defined as 12 consecutive months with no menses without an 
alternative medical cause 
7. Males must agree to 
a. use protocol defined methods of contraception and  
b. refrain from donating sperm for the duration of the study and 90 days after their last 
dose of the investigational product 
8. Have vaccination against Streptococcus pneumoniae, N meningitidis (types A, C, W, Y, 
and B), and H influenzae (type B) either within 5 years prior to baseline visit 2b, or agree 
to receive vaccination at least 7 days prior to baseline visit 2b. Vaccination is mandatory, 
unless documented evidence exists that subjects are non-responders to vaccination 
(as evidenced by titers or display titer levels within acceptable local limits)   
9. Willing and able to give informed consent and comply with study procedure and 
assessments (including at-home assessments) 
7.2. 
Subject Exclusion Criteria 
1. Confirmed or suspected other causes of neuromuscular weakness 
2. Diagnosis of another neurodegenerative disease(s)  
3. Subject with significant cognitive impairment, clinical dementia, or psychiatric illness 
that in the opinion of the investigator may increase subject’s risk by participating in the 
study or confound the outcome of the study 
4. Subjects with a significant pulmonary disorder not attributed to ALS or who require 
treatments that might complicate the evaluation of the effect of ALS on respiratory 
function (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, 
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5. Current use or anticipated need, in the opinion of the investigator, of a diaphragm pacing 
system (DPS) during the randomized treatment period 
6. Riluzole initiation or change in dose within 30 days prior to the start of the screening 
period or planned initiation during study participation. If using riluzole, the subject 
should remain on the drug throughout Part 2 of study participation, but the dosage may be 
altered or the drug discontinued at any time by the investigator for any safety concern. 
Riluzole-naïve subjects are allowed in the study. 
7. Edaravone initiation or change in dose within 60 days prior to the start of the screening 
period or planned initiation during study participation. If using edaravone, the subject 
should remain on the drug throughout Part 2 of study participation, but the dosage may be 
altered or the drug discontinued at any time by the investigator for any safety concern. 
Edaravone-naïve subjects are allowed in the study. 
8. Positive response to Item 4 or 5 of the C-SSRS 
9. Subjects with detectable hepatitis C by polymerase chain reaction at screening 
10. Subjects with chronic inactive hepatitis B with viral loads >1000 IU/mL 
(>5000 copies/mL) at screening. Eligible subjects who are chronic active carriers 
(≤1000 IU/mL) must receive prophylactic antiviral treatment according to local country 
guidelines (eg, entecavir, tenofovir, lamivudine) 
11. History of an aggressive lymphoma or presence of a lymphoma requiring therapy by itself 
12. Active or overt malignant disease other than basal cell carcinoma or cutaneous squamous 
cell carcinoma 
13. Received organ transplant 
14. Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase, 
aspartate aminotransferase, or bilirubin levels >2 × the upper limit of normal  
15. Presence or suspicion of severe recurrent or chronic infections that, in the opinion of the 
investigator, increase the subject’s risk by participating in the study 
16. Participation in any other investigational drug trial or exposure to other investigational agent, 
device, or procedure within 30 days or within 5-half lives of the treatment (whichever is 
longer) prior to the start of the screening period or during study participation 
17. Use of any other complement inhibitor within 30 days or within 5-half lives of the treatment 
(whichever is longer) prior to the start of the screening period or during study participation 
18. If breastfeeding, unwilling to discontinue for the duration of the study and for at least 
6 months after final dose of investigational product 
19. Inability to cooperate or any condition that, in the opinion of the investigator, could increase 
the subject’s risk by participating in the study or confound the outcome of the study 
20. Subjects with known allergy or hypersensitivity to pegcetacoplan or to any of the 
components 
21. Known or suspected hereditary fructose intolerance 

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7.3. 
Subject Completion and Withdrawal Criteria 
Subjects will be considered to have completed the study when they have: 
• Completed the open-label long-term extension period. 
Subjects will be considered to have withdrawn from the study when they have: 
• Completed any early termination activities. 
A subject may withdraw from the study at any time, for any reason, without prejudice to his/her 
future medical care by the physician or at the institution. The investigator or sponsor may 
withdraw the subject at any time (eg, in the interest of the subject’s safety). If a subject 
discontinues or is withdrawn from the investigational product for any reason, the study site must 
immediately notify the medical monitor. Once a subject is withdrawn from the study, the subject 
may not re-enter the study. 
Subjects who discontinue the investigational product prior to the follow-up (core)/follow-up 
(open-label)/follow-up (open-label, long-term extension) visits will undergo all remaining visits 
and procedures through the relevant follow-up visit, unless unwilling or unable, or consent has 
been withdrawn. Subjects who wish to fully withdraw from the study before completion will 
complete the early termination follow-up visit 6 weeks (±7 days) after their last dose of the 
investigational product (see Table 2, Table 3, and Table 8). 
If a subject withdraws from the study, then the subject and/or their caregivers will be contacted 
by the study site to provide post-discontinuation survival status at 6-month intervals until the 
study completes. 
7.3.1. 
Reasons for Discontinuation 
The reason for withdrawal must be determined by the investigator and recorded in the subject’s 
medical record and on the electronic case report form (eCRF). If a subject is withdrawn for more 
than 1 reason, each reason should be documented in the source document and the most clinically 
relevant reason should be entered on the eCRF. 
The following list includes the reasons for discontinuation from treatment and/or withdrawal 
from the study: 
• adverse events 
• death 
• lost to follow-up 
• withdrawal by subject 
• study terminated by sponsor 
• physician decision 
• pregnancy 

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• major protocol violation deemed, after consultation with study medical monitor, 
to potentially impact the subject’s safety and study data interpretation 
• lack of efficacy, defined as inadequate response to study drug in the investigator’s 
opinion 
7.3.1.1. 
Mandatory Study Discontinuation/Withdrawal Criteria 
Subjects are required to discontinue the investigational product and withdraw from the study if 
they meet the below criteria: 
• Administer a complement inhibitor during the period outlined in Section 8.6.1  
• Intentionally unblinded themselves  
7.3.2. 
Subjects “Lost to Follow-up” Prior to Last Scheduled Visit 
A minimum of 3 documented attempts must be made to contact any subject lost to follow-up at 
any time point prior to the last scheduled contact. At least 1 of these documented attempts must 
include a written communication sent to the subject’s last known address via courier or mail 
(with an acknowledgement of receipt request) asking that he/she return to the site for final safety 
evaluations and to return any unused investigational product and study devices. 

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8. 
TREATMENT OF SUBJECTS 
8.1. 
Identity of the Investigational Product 
Throughout this protocol, “investigational product” refers to the blinded treatment, whether that 
is pegcetacoplan or placebo. Additional information on pegcetacoplan and placebo is available in 
Section 9. 
8.2. 
Treatment Assignment 
8.2.1. 
Blinding the Treatment Assignment 
This is a randomized, double-blinded, placebo-controlled study. The intent of blinding is to limit 
the occurrence of conscious and unconscious bias in the conduct and interpretation of the clinical 
study. Bias could arise from the influence that the knowledge of a specific treatment assignment 
may have on the recruitment and allocation of subjects, their subsequent care, the assessment of 
endpoints, the handling of withdrawals, and so on. The essential aim of blinding, therefore, is to 
prevent identification of the treatments by the subject and the blinded assessors associated with 
the conduct of the study until all such opportunities for bias have passed. 
Designated blinded study staff (eg, research coordinators, nurses, technicians administering 
questionnaires, subjects, spirometry and dynamometer central reading centers, assigned 
evaluating physician(s), and the sponsor) will be blinded to treatment assignment. Only the drug 
supply distributor/logistics personnel who are not site personnel will be unblinded to study 
treatment. These individuals are not allowed to discuss treatment and/or subject outcome with 
blinded study staff, including the evaluating physician. The principal investigator must be 
blinded to subjects’ treatment assignment.  
8.2.2. 
Randomization 
To prevent bias in treatment assignment, randomization will occur through the interactive 
response technology system.  
The randomization will only be available to the drug supply distributor/logistics personnel. 
The randomization will not be made available to the sponsor, subjects, or clinic staff responsible 
for the monitoring and evaluation of safety assessments. 
All subjects who meet all the inclusion criteria and none of the exclusion criteria will be enrolled in 
the study, until such time that approximately 228 subjects have been enrolled in the study. At the first 
visit of the randomized treatment period, subjects will be randomized after confirmation of study 
eligibility in a ratio of 2:1 via a computer-generated randomization schedule to receive pegcetacoplan 
or placebo. The randomization will be performed centrally and stratified by location of first muscle 
weakness (limb or bulbar), riluzole, and edaravone use. The stratification by location of onset and 
riluzole and edaravone use will ensure balance between treatment groups for the respective 
stratification factors. Fixed block randomization will be used to ensure that approximately equal 
number of subjects are assigned each treatment within strata.  

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vaccination (as evidenced by titers or display titer levels within acceptable local limits). 
The investigator will discuss with the sponsor regarding individual subject circumstances.  
If the subject requires vaccination against N meningitidis, both vaccinations (N meningitidis A, 
C, W, Y and N meningitidis B) should be administered at least 7 days prior to baseline visit 2b. 
If the subject requires vaccination against Streptococcus pneumoniae, PCV13 will be 
administered at least 7 days prior to baseline visit 2b, and PPSV23 will be administered after at 
least 8 weeks.  
Revaccination should be consistent with the recommendations of the Centers for Disease Control 
and Prevention (or local guidelines) as follows:  
• N meningitidis types A, C, W, Y: every 5 years 
• N meningitidis type B: 1 year after the primary series and repeated every 2-3 years  
• Streptococcus pneumoniae (PPSV23):  5 years after previous PPSV23 dose  
• Haemophilus influenzae type B (Hib vaccine): no revaccination needed 
It is recommended that subjects also be vaccinated annually against influenza (flu) during study 
participation in accordance with guidelines in the country of residence. 
8.4.1. 
Prophylactic Antibiotics 
Administration of prophylactic antibiotic therapy chronically may be conducted, at the discretion 
of the treating investigator, in accordance with local treatment guidelines. 
8.5. 
Concomitant Medications 
All medications administered and procedures performed within 12 weeks of screening will be 
collected as prior medications and procedures. Medications administered and procedures 
performed from the time of informed consent through the early termination follow-up/follow-up 
(core)/follow-up (open-label)/follow-up (long-term extension) visit will be documented.  
• Use of riluzole during the study is allowed as long as the subject remains on the drug 
throughout Part 2 of study participation, but the dosage may be altered or the drug 
discontinued by the investigator at any time for any safety concern. Riluzole initiation 
or change in dose within 30 days prior to the start of the screening period or during 
Part 2 of study participation is not allowed. Riluzole-naïve subjects are allowed in 
study. If riluzole is initiated or discontinued or if dose is changed during Parts 3 or 4 
of the study, the dates of administration must be documented in the subject’s source 
document and subject’s eCRF. 
• Use of edaravone during the study is allowed as long as the subject remains on the 
drug throughout Part 2 of study participation, but the dosage may be altered or the 
drug discontinued at any time by the investigator for any safety concern. Edaravone 
initiation or change in dose within 60 days prior to the start of the screening period or 
during Part 2 of study participation is not allowed. Edaravone-naïve subjects are 
allowed in study. If edaravone is initiated or discontinued or if dose is changed during 
Parts 3 or 4 of the study, the dates of administration must be documented in the 
subject’s source document and subject’s eCRF. 

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• Subjects should not begin Relyvrio (AMX0035) during Part 2 of the study and if 
administered during Part 3 or 4, the dates of administration must be documented in 
the subject’s source document and subject’s eCRF. 
Concomitant treatment refers to all treatment taken between the dates of the first dose of 
investigational product and the end of the follow-up period, inclusive. Concomitant treatment 
information must be recorded on the appropriate eCRF page. Except for complement inhibitors 
(other than pegcetacoplan [eg, eculizumab or ravulizumab]), any concomitant medication 
deemed necessary for the subject’s standard of care during the study, or for the treatment of any 
AE (along with the allowed medications described below) may be given at the discretion of the 
investigator. It is the responsibility of the investigator to ensure that the details regarding all 
medications are recorded in full in the subject’s eCRF. 
8.6. 
Prohibited Medications or Procedures 
8.6.1. 
Prohibited Medications 
Subjects are prohibited from taking the below medications: 
• Any other complement inhibitor within 30 days or within 5-half lives of the treatment 
(whichever is longer) prior to the start of the screening period or during study 
participation 
8.6.2. 
Prohibited Procedures 
Subjects are prohibited from having a DPS implanted prior to or during Part 2. Subjects who 
have a DPS implanted during Part 2 will be required to withdraw from the study. If a subject has 
a DPS implanted during Part 3 or 4, the date of the implantation must be documented in the 
subject’s source document and subject’s eCRF. 
8.7. 
Treatment Compliance 
Investigational product accountability will be performed to ensure subjects are dosing according 
to assigned treatment group. Subjects should not skip or deviate from their dosing schedule: 
day 1 and day 4 of each treatment week (eg, Tuesday/Friday/Tuesday). Dosing will be recorded 
in the dosing diaries.  
Subjects must be instructed to bring their empty/unused investigational product packaging to 
every visit. The pharmacist/nominated person will record details on the drug accountability form. 
Refer to the Pharmacy Manual for further details. 

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9. 
INVESTIGATIONAL PRODUCT MATERIALS AND 
MANAGEMENT 
9.1. 
Investigational Product 
9.1.1. 
Pegcetacoplan  
Pegcetacoplan (also known as APL-2) drug product (DP) solution for injection or infusion will be 
provided as a sterile solution of pegcetacoplan with a concentration of 54 mg/mL in 10 mM acetate 
buffer, pH 5.0, containing 4.1% sorbitol supplied in stoppered glass vials. Additional information is 
provided in the pegcetacoplan DP IB.  
9.1.2. 
Placebo 
Placebo will be provided as a sterile solution of 10 mM acetate buffer, pH 5.0, containing 4.1% 
sorbitol supplied in stoppered glass vials. 
9.2. 
Investigational Product Packaging and Labeling 
9.2.1. 
Packaging 
Investigational product is supplied in 20-cc glass vials. Please refer to the Pharmacy Manual for 
details. 
Changes to sponsor-supplied packaging prior to dosing may not occur without full agreement, 
in advance, by the sponsor. 
9.2.2. 
Labeling 
Labels containing study information and pack identification are applied to the investigational 
product container. 
All investigational product (pegcetacoplan DP or placebo) is labeled with a minimum of the 
following: protocol number, dosage form (including product name and quantity in pack), route of 
administration, directions for use, storage conditions, batch number and/or packaging reference, 
statements required per local regulations (eg, “For clinical trial use only”), and name and address 
of the sponsor. 
Space is allocated on the label so that the clinic representative can record a unique subject 
identifier and date dispensed. 
Additional labels may, on a case-by-case basis, be applied to the investigational product in order to 
satisfy national, local, or institutional requirements but must not do any of the following: contradict 
the clinical study label, obscure the clinical study label, identify the study subject by name. 
Additional labels may not be added without the sponsor’s prior full agreement. 
9.3. 
Investigational Product Storage and Handling 
The investigational product is to be stored refrigerated at 2 to 8°C.  

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If the investigational product is stored at investigator site (or documented storage location 
outside of subjects’ home), temperature monitoring is required to ensure that the investigational 
product is maintained within the established temperature range (2 to 8°C).  
The site pharmacist is responsible for the following: 
• ensuring that the investigational product is stored in a secure, limited-access location 
at the site 
• ensuring that the temperature is monitored throughout the duration of the study when 
the investigational product is at site and/or shipped to subject  
• ensuring that investigational product and supply records are maintained 
• dispensing the vials of investigational product to the subject and/or caregiver 
• entering the unique subject identifier on the investigational product bottle/carton 
labels as they are distributed 
The investigator or trained research personnel is responsible for ensuring subjects and/or 
caregivers are trained on how to appropriately store the investigational product. 
If the subject receives the investigational product from the site, it should be transported in a 
sponsor-approved bag or box, containing previously temperature-conditioned cold plates to 
ensure that the storage temperature (2 to 8°C) is maintained. Temperature monitoring will not be 
required at the subject’s residence. 
With sponsor prior approval, investigational product and/or ancillary supplies may be shipped from 
the study site to a subject’s designated location. Such shipments will be implemented only at sites 
where this activity is approved by the IRB/IEC and health authority (if required). Subject consent 
will be required prior to any subject information being provided to a courier. The responsibility to 
return empty vials and any unused investigational product shall remain unchanged. 
9.4. 
Administration 
The investigational product will be administered as a 20-mL SC infusion.  
The preferred site of infusion will be the abdomen. If administration into the abdomen is not feasible, 
alternative appropriate sites are acceptable (see Pump Instructions for Use for more details).  
Nurses or other research personnel will train and supervise the self-administration of SC 
infusions. The nurses/research personnel will be made available for a minimum of 6 days on 
treatment (2 doses) to ensure the subject or caregiver has been trained to conduct administration; 
the duration could be shortened if ability to self-administer happens sooner. During training, 
the subject (or caregiver) must demonstrate to the research personnel his/her ability to safely and 
effectively administer study drug using the infusion pump. Following self-administration 
training, subjects (or caregiver) may self-administer the SC infusions without supervision. 
If subject (or caregiver) is unable to self-administer study drug, a nurse may be made available 
for longer periods of time for study drug administration following consultation with the sponsor. 

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9.5. 
Infusion Supplies  
The sponsor will supply syringes, vial adapters, infusion sets, and ambulatory syringe infusion 
pumps, as required. Refer to the Pharmacy Manual for further details. 
9.6. 
Investigational Product Accountability 
Accountability for the investigational product at the study center is the responsibility of the 
investigator. The investigator will ensure that the investigational product is used only in accordance 
with this protocol. Where allowed, the investigator may choose to delegate investigational product 
accountability responsibilities to a pharmacist or other appropriate individual. 
Investigators will be provided with sufficient amounts of the investigational product to carry out 
this protocol for the agreed number of subjects. The investigator/designee will acknowledge 
receipt of the investigational product, and documenting shipment content and condition. 
Accurate records of all investigational product dispensed, used, returned, and/or destroyed must 
be maintained. Accountability records will include dates, quantities, batch/serial numbers, 
expiration dates (if applicable), and participant numbers. The sponsor/designee will review 
investigational product accountability at the study center on an ongoing basis during monitoring 
visits. Investigational product must not be used for any purpose other than the present study. 
Investigational product that has been dispensed to a participant and returned unused must not be 
re-dispensed to a different participant. The investigator is responsible for ensuring the retrieval of 
all returnable study supplies from subjects. 
9.7. 
Investigational Product Disposal 
All unused and used study drug vials should be retained at the center until they are inventoried 
by the study monitor. At the conclusion of the study, any unused investigational product will 
either be destroyed or be returned to the sponsor or designee for destruction, and destruction will 
be documented appropriately. If no supplies remain, this fact will be documented appropriately. 

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10. 
EFFICACY AND EXPLORATORY ASSESSMENTS 
10.1. 
Efficacy Assessments 
10.1.1. 
Primary Efficacy Assessment 
The primary efficacy assessment is the difference in the CAFS score at week 52. 
10.1.1.1. CAFS Scale 
The CAFS scale is a combined endpoint ranking subjects’ clinical outcomes based on ALSFRS-R 
and survival time. The worst outcome is assigned to the subject who dies first in the study and the 
best is assigned to the subject who survives with the least functional decline. Each subject’s outcome 
is compared to every other subject outcome in the trial in a series of pairwise comparisons, and the 
summed scores are ranked. A higher mean CAFS score indicates a better group outcome. 
Analysis will be completed by the sponsor. 
10.1.1.1.1. ALSFRS-R Scale 
The ALSFRS-R is a validated rating scale used to assess physical function in subjects with ALS. 
There are 12-items across 4 domains encompassing bulbar function, respiratory function, fine 
motor function, and gross motor function. Each question is scored from 0 (worst function) 
to 4 (best function), for a total maximum score of 48. The ALSFRS-R has been correlated to 
disease progression and survival and is validated for administration over the telephone to the 
subject. If the subject is unable to complete the ALSFRS-R assessment, the ALSFRS-R may be 
administered over the telephone to the caregiver (and must continue to be administered to the 
same caregiver for the rest of the subject’s participation in the study). In this study, ALSFRS-R 
will be assessed by qualified research personnel via the telephone during monthly telephone 
visits and on a dosing day within the visit window prior to clinic visits (except for screening). 
10.1.2. 
Secondary Efficacy Assessments 
The following are the secondary efficacy assessments for this study: 
• Change from baseline in ALSFRS-R at week 52  
• Change from baseline in %SVC (at clinic visits) at week 52  
• Change from baseline in HHD megascore at week 52 
• Change from baseline in ALSAQ-40 at week 52 
• Time to death, permanent tracheostomy, or permanent assisted ventilation up to week 52  
• Time to death up to week 52 
• Change from baseline of the randomized treatment period (visit 2) and of the open-label 
treatment period (visit 15) to week 104 for ALSFRS-R, %SVC, and HHD  
• Time to death, permanent tracheostomy, or permanent assisted ventilation up to 
week 104 
•  Time to death up to week 104 

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10.1.2.1. Slow Vital Capacity—Clinic 
Slow vital capacity is a pulmonary function test measured during spirometry which reflects the 
maximum amount of air that can be exhaled slowly. The %SVC is the percentage of the 
predicted SVC value based on age, sex, and height. Slow vital capacity has been shown to 
closely correlate with forced vital capacity and is a predictor of functional loss in ALS.  
Slow vital capacity will be conducted at clinic visits with the clinic spirometer. 
10.1.2.2. ALSAQ-40 
The ALSAQ-40 is a 40-item validated questionnaire designed to assess HRQoL over the previous 
2 weeks in subjects with ALS or other MN diseases. The instrument measures 5 dimensions of health 
status: physical mobility, activities of daily living and independence, eating and drinking, 
communication, and emotional functioning. Dimension scores are converted to a scale of 0 
(perfect health as assessed by the measure) to 100 (worse health as assessed by the measure). 
The ALSAQ-40 will be administered at clinic visits. 
10.1.2.3. Handheld Dynamometry  
Handheld Dynamometry (HHD) is a quantitative method to measure muscle strength used in 
subjects with ALS. Assessments will be evaluated by combined muscle groups called 
megascores, which average scaled individual strength measures to produce an overall measure. 
Strength expressed as megascores have been shown to decline with ALS disease progression.  
The muscle groups that will be assessed are: first dorsal interosseous, wrist extension, elbow 
extension, elbow flexion, shoulder flexion, knee extension, knee flexion, and ankle dorsiflexion, 
on both sides of the body. HHD will be administered at clinic visits by qualified research personnel.  
10.2. 
Exploratory Assessments 
The following are the exploratory assessments for this study: 
• Change from baseline in EQ-5D-5L at week 52, week 104, and week 156 
• Change from baseline in ZBI score at week 52, week 104, and week 156 
• Change from baseline of %SVC (home spirometry) at week 52 and week 104 
• Time to percutaneous endoscopic gastrostomy tube placement up to week 52, 
week 104, and week 156 
• Change from baseline in serum NfL at week 52, week 104, and week 156 
• Change from baseline in serum pNfH at week 52, week 104, and week 156 
• Change from baseline in EIM at week 52, week 104, and week 156 (only at select 
investigational sites chosen to complete this) 
• Pegcetacoplan PK concentrations at week 52, week 104, and week 156 

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• Changes from baseline at week 52, week 104, and week 156 in complement biomarkers: 
− 
CH50 
− 
AH50 
− 
C3 levels 
• Immunogenicity: presence of antibodies to PEG moiety and peptide moiety of 
pegcetacoplan during the randomized and open-label treatment periods 
• Change from baseline of the randomized treatment period (week 1) and of the 
open-label treatment period (week 52) to week 156 for ALSFRS-R, %SVC 
(in-clinic), HHD, and ALSAQ-40 
• Time to death, permanent tracheostomy, or permanent assisted ventilation up to 
week 156 
• Time to death up to week 156 
10.2.1. 
EQ-5D-5L 
The EQ-5D-5L is a standardized measure of health status developed to assess HRQoL by the 
EuroQoL Group. The questionnaire consists of a descriptive system and a visual analogue scale. 
The descriptive system contains 5 dimensions (mobility, self-care, usual activities, pain/discomfort, 
and anxiety/depression) with 5 levels in each dimension.  
EQ-5D-5L will be administered by qualified research personnel via the telephone during monthly 
telephone visits and within the visit window prior to clinic visits (but not in clinic).  
10.2.2. 
Zarit Burden Interview  
The ZBI is a 22-item self-reported measurement of caregiver burden. The caregiver responds to each 
item regarding the impact of the subject’s disability on their life using a 5-point scale from 0 (Never) 
to 4 (Nearly Always). The total minimal score is 0 and the maximum score is 88, with higher scores 
signifying increased burden. The ZBI has been used in several studies to assess burden in caregivers 
of subjects with ALS. 
The ZBI must be administered to the same caregiver throughout the subject’s study participation. 
“Caregiver” is defined as the family member who lives with the subject, or individual who spends 
the most time providing physical and/or emotional care to the subject. The ZBI should not be 
administered by third party home care support staff. If the subject is not actively being assisted by a 
caregiver at baseline, ZBI will be administered to the subject’s anticipated caregiver. If the subject 
does not have an anticipated caregiver/relative at baseline, ZBI administration will begin when/if the 
subject starts requiring a caregiver.  
The ZBI will be administered by qualified research personnel via the telephone during monthly 
telephone visits and within the visit window of clinic visits (but not in clinic).  

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10.2.3. 
Slow Vital Capacity—Home 
As outlined in Section 10.1.2.1, slow vital capacity is a pulmonary function test measured during 
spirometry that reflects the maximum amount of air that can be exhaled slowly. The %SVC is the 
percentage of the predicted SVC value based on age, sex, and height. Slow vital capacity has been 
shown to closely correlate with forced vital capacity and is a predictor of functional loss in ALS.  
Slow vital capacity will be conducted once per week at home on a dosing day (with the exception of 
visit 2b) with a handheld spirometer. Slow vital capacity measured at subject’s home will be 
collected via the GoSpiro device and transmitted to a provisioned device via Bluetooth radio. 
The data stored on the device is then sent to the CarePortal (data platform) via Wi-Fi or cellular 
transmission. The subject and/or caregiver will receive training from a research nurse or other 
research personnel on the use of the spirometer for home use.  
10.2.4. 
Neurofilaments 
Neurofilaments are intermediate filaments and structural proteins of neurons. The most 
commonly- assessed neurofilament subunits in clinical trials are NfL and pNfH. Neurofilament 
levels in serum and cerebral spinal fluid are reflective of neuronal injury and both NfL and pNfH 
have been shown to correlate with extent of clinical upper and lower MN involvement in 
subjects with ALS. 
In this study, neurofilaments will be assessed with a blood sample.  
10.2.5. 
Electrical Impedance Myography  
Electrical impedance myography is a noninvasive, electrophysiological technique that has been 
shown to correlate with ALS disease progression. In this assessment, a high frequency, low-intensity 
electrical current is applied to a limb with the device and the resulting voltages are measured in the 
muscle. Changes in muscle structure such as atrophy, are detected as a change in impedance.  
Electrical impedance myography measurements will be performed bilaterally on the following 
muscles: quadriceps, tibialis anterior, gastrocnemius, wrist extensor compartment, biceps, 
and deltoids.  
Only select investigational sites will be chosen to perform this assessment on their subjects. 
Electrical impedance myography will be completed prior to HHD. 

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11. 
SAFETY ASSESSMENTS 
11.1. 
Safety Parameters 
11.1.1. 
Demographic/Medical History 
Medical history will be recorded at screening. Investigators should document the occurrence, signs, 
and symptoms of the subject’s pre-existing conditions, including all prior significant illnesses, up to 
and including 1 year before screening. Additional preexisting conditions, present at the time when 
informed consent is given, up to the time of first dosing, are to be regarded as concomitant. 
Medical history will include alcohol consumption and smoking history, if applicable. 
Information regarding genetic markers, identified to be linked to ALS, will also be collected, 
if available (Section 11.1.10). 
Illnesses first occurring or detected during the study and/or worsening of a concomitant illness 
during the study are to be documented as AEs on the eCRF in accordance with Section 11.5.  
Additionally, demographic data will be collected for all subjects, as allowed per applicable 
regulations. 
11.1.2. 
Vital Signs 
Vital signs (body temperature, respiration rate, heart rate, and systolic and diastolic blood 
pressure measurements) will be evaluated at the visits indicated in the schedule of assessments 
tables (Table 2, Table 3, and Table 8). All vital signs will be measured after the subject has been 
resting in a sitting position for at least 5 minutes, except when they are supine or semireclined 
because of study procedures and/or AEs, or if deemed necessary by the investigator. Blood 
pressure measurements are to be taken in the same arm for the duration of the study.  
Vital sign measurements will be repeated, if clinically significant or if machine/equipment errors 
occur. Out-of-range blood pressure, respiratory rate, or heart rate measurements will be repeated, 
at the investigator’s discretion. Any confirmed, clinically significant vital signs measurements 
must be recorded as AEs. 
When investigational product is administered at the clinic, vital signs will be measured within 
2 hours preinfusion and at 30 minutes (±5 minutes) postdose.  
11.1.3. 
Electrocardiogram  
All 12-lead electrocardiograms (ECGs) will be measured once, prior to dosing (if applicable), 
at the time points outlined in the schedule of assessments (Table 2, Table 3, and Table 8). 
The ECG will be taken following resting in the supine position for at least10 minutes in a quiet 
environment and prior to any blood sampling procedures. The ECGs will be classified as normal, 
having a not clinically significant abnormality, or having a clinically significant abnormality. 
In addition, ECG parameters of ventricular rate, PR interval, QRS duration, and QT internal 
(uncorrected and corrected using Fridericia’s method) will be reviewed for ongoing safety. 
11.1.4. 
Weight and Height 
Body weight and height (both assessed without shoes on) will be recorded as outlined in the 
schedule of assessments (see Table 2, Table 3, and Table 8). 

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11.1.5. 
Physical Examination 
All full physical examinations, performed by the investigator or designee, will include, at a 
minimum, assessment of the following: general, head, ears, eyes, nose, throat, dentition, thyroid 
(endocrine), heart, chest, lungs, abdomen, skin, extremities, back/neck, musculoskeletal, 
and lymph nodes.  
Brief physical examinations will include general appearance, heart, lungs, abdomen, extremities, 
and weight and are to be performed at all visits where a full physical examination does not occur.  
Additional symptom-driven physical examinations may be performed at any time, as deemed 
necessary by the investigator.  
See the schedule of assessments (Table 2, Table 3, and Table 8) for the details regarding which 
type of physical examination should be given at each visit. 
11.1.6. 
Injection/Infusion Site/Pump Safety Assessment 
Subjects (and/or caregivers) will be trained to administer the investigational product in the study.  
Subjects will be instructed to notify the investigator or other study personnel if an 
injection/infusion site reaction occurs after self-administration of pegcetacoplan. All clinically 
significant findings related to injection/infusion procedures will be recorded as AEs. 
11.1.7. 
C-SSRS 
The C-SSRS is a measure used to identify and assess individuals at risk for suicide. 
The questionnaire will assess suicidal thoughts and actions over the subject’s lifetime, prior 
6 months from screening and baseline, and changes from clinic visits. Questions are phrased for 
use in an interview format but can be completed as a self-report measure if necessary. 
The C-SSRS measures 4 constructs: the severity of ideation, the intensity of ideation, behavior, 
and lethality and is made up of 10 categories. The outcome of the C-SSRS is a numerical score 
obtained from the aforementioned categories. 
11.1.8. 
Laboratory Assessments 
Laboratory assessment samples (Table 4) are to be obtained at designated visits as detailed in the 
schedule of assessments tables (Table 2, Table 3, and Table 8). 
Labs will include, but will not be limited to, the following: 
 

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Table 4: 
Laboratory Assessments 
Hematology 
Serum Chemistry 
Urine Studies 
Hb 
Hematocrit 
Platelet count 
RBC count 
WBC count with differential 
 
Albumin 
ALT 
ALP 
AST 
Bicarbonate 
Bilirubin (total, direct, and 
indirect) 
BUN 
Calcium 
Chloride 
Creatinine 
Creatine kinase  
Estimated glomerular filtration 
rate (using CKD-EPI 
formula) 
GGT 
Glucose 
HDL 
LDL 
Phosphorus 
Potassium 
Sodium 
Triglycerides 
Total cholesterol 
Total protein 
Uric acid 
Urinalysis 
• 
Blood 
• 
Bilirubin  
• 
Glucose 
• 
Ketones 
• 
Leukocyte esterase 
• 
Microscopic examination of 
urine sediment, including 
for presence of RBCs, 
WBCs, and casts, will be 
performed on all urinalyses 
• 
Nitrite 
• 
pH 
• 
Pregnancy, when applicable 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 
Neurofilaments  
Additional 
NfL 
pNfH 
FSH (postmenopausal women) 
HBsAg 
HCV 
Serum pregnancy test 
Complement activation tests: 
(C3, AH50, and CH50) 
Anti–pegcetacoplan peptide antibody and anti-PEG antibody  
Abbreviations: AH50 = 50% alternative hemolytic complement pathway activity; ALP = alkaline phosphatase; ALT = alanine 
aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CH50 = 50% classical hemolytic complement 
pathway activity; CKD-EPI = Chronic Kidney Disease–Epidemiology Collaboration; FSH = follicle-stimulating hormone; 
GGT = gamma-glutamyltransferase; Hb = hemoglobin; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; 
HDL = high-density lipoproteins; LDL = low-density lipoproteins; NfL = neurofilament light chain; pNfH = phosphorylated 
neurofilament heavy chain; RBC = red blood cells; WBC = white blood cells. 
Note: The use of silica reagents in coagulation panels should be avoided in subjects treated with pegcetacoplan due to possible 
interference resulting in artificially prolonged aPTTs. Please refer to the IB for more details. 

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Blood and urine samples will be analyzed at a central laboratory facility, as defined in the Laboratory 
Manual. Urine samples will be analyzed by dipstick and a microscopic analysis. All laboratory 
reports must be reviewed, signed, and dated by the investigator. A legible copy of all reports must be 
filed with both the subject’s eCRF and medical record (source document) for that visit.  
Clinically significant abnormal values occurring during the study will be followed up until repeat 
test results return to normal, stabilize, or are no longer clinically significant. 
Table 5 shows the blood volumes collected for the study. 
Table 5: 
Blood Volumes Collected 
Assay 
Number of collection  
time points 
Approximate volume 
per time point* (mL) 
Approximate sample 
volume over course 
of study (mL) 
Chemistry  
Screening: 1 
Randomized treatment 
visits: 6 
Open-label visits: 4 
Open-label Long-Term 
Extension:  4 
3.5 or 5.0 mL 
52.5 – 75.0 
HBsAg, HCV 
Screening: 1 
8.5 
8.5 
CH50 
Randomized treatment 
visits: 6 
Open-label visits 4 
Open-label Long-Term 
Extension:  4 
4.0 
56.0 
AH50 
Randomized treatment 
visits: 6 
Open-label visits: 4 
Open-label Long-Term 
Extension:  4 
4.0 
56.0 
NfL and pNfH 
Randomized treatment 
visits: 6 
Open-label visits: 4 
Open-label Long-Term 
Extension:  4 
5.0 
70.0 
Pharmacokinetics 
Randomized treatment 
visits: 6 
Open-label visits: 4 
Open-label Long-Term 
Extension:  4 
4.0 
56.0 
Anti–pegcetacoplan 
peptide and anti-PEG 
Ab 
Randomized treatment 
visits: 6 
Open-label visits: 4 
Open-label Long-Term 
Extension:  4 
4.0 
56.0 

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Table 5: 
Blood Volumes Collected 
Assay 
Number of collection  
time points 
Approximate volume 
per time point* (mL) 
Approximate sample 
volume over course 
of study (mL) 
Hematology 
Screening: 1 
Randomized treatment 
visits: 6 
Open-label visits: 4 
Open-label Long-Term 
Extension:  4 
2.0 
30.0 
Total 
385 – 407.5 
Abbreviations: Ab = antibody; AH50 = 50% alternative hemolytic complement pathway activity; CH50 = 50% classical 
hemolytic complement pathway activity; HBsAg = surface antigen of the hepatitis B virus; HCV = hepatitis C virus; 
NfL = neurofilament light chain; PEG = polyethylene glycol; pNfH = phosphorylated neurofilament heavy chain.  
11.1.8.1. Pregnancy Screen 
For WOCBP, a serum pregnancy test will be performed at screening. Subjects with a positive 
result will be excluded or discontinued from the study. A urine pregnancy test will also be 
performed starting at baseline and at all indicated visits in the schedule of assessments (Table 2, 
Table 3, and Table 8). Male subjects will be counseled to avoid donating semen during the time 
between the first screening and the final follow-up (core)/follow-up (open-label)/open-label, 
long-term extension), and early termination follow-up visit and for 90 days after their last dose of 
investigational product. 
11.1.9. 
Anti–Pegcetacoplan Peptide Antibody and Anti-PEG Antibody Assessments 
The proposed anti-drug antibodies (ADA) sampling schedule was established to capture the 
ADA signal at baseline, along with any potential early onset and the dynamic profile (transient or 
persistent) of antibody formation.  
Samples that test positive will be characterized by an assay that will determine antibody titer and 
measure neutralizing capacity. Discontinued subjects will have ADA follow-up every 6 months 
from last dose until it can be determined that the subject’s antibody levels are at baseline or that 
further testing is not needed.  
Subjects will need to have ADA samples collected as outlined in the schedule of assessments 
(Table 2, Table 3, and Table 8). 
11.1.10. 
Genetic Mutation(s) Results 
Testing for genetic mutations is not performed as part of the study. However, subjects who have 
confirmed genetic mutations linked with ALS (eg, C9orf72, TARDBP, FUS, etc.) will be asked to 
provide this information, which will be documented as part of their medical history. Providing 
genetic mutations testing results is optional and a subject’s decision to not provide this information 
does not preclude them from participating in the study, if eligible. Genetic mutation data will be used 
in analysis for correlation with outcomes. 

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11.1.11. 
COVID-19 Assessment 
If a subject has been tested for COVID-19, the results, if available, will be documented via eCRF. 
11.2. 
Adverse and Serious Adverse Events 
11.2.1. 
Definitions 
11.2.1.1. Adverse Events 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not it is considered drug related. An AE can, therefore, be any unfavorable and unintended 
sign, including a clinically significant abnormal laboratory finding, symptom, or disease 
temporally associated with the use of an investigational product, whether or not considered 
related to the investigational product. 
Adverse events can be spontaneously reported by the subject and/or in response to an open 
question from the study personnel or revealed by observation and will be recorded during the 
study at the investigational site. All identified AEs must be recorded and described on the 
appropriate AE or SAE page of the eCRF.  
Fluctuating or nonsignificant changes in laboratory values do not necessarily qualify for AE 
reporting. If changes in laboratory values are assessed as clinically significant and/or lead to 
discontinuation of administration of investigational product, they should be reported as an AE. 
If these laboratory values are linked to a diagnosis, only the diagnosis should be reported as an AE. 
11.2.1.2. Unexpected Adverse Event 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Reference Safety Information section of the investigator brochure (IB) that is in effect at the time 
of event onset. 
11.2.1.3. Serious Adverse Events 
An SAE is any AE or suspected adverse reaction that, in the view of the investigator, results in 
death, is life threatening, requires inpatient hospitalization or prolongation of existing 
hospitalization, results in a persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions, or is a congenital anomaly or birth defect.  
Important medical events that may not result in death, be life threatening*, or require 
hospitalization may be considered serious when, according to appropriate medical judgment, 
they may jeopardize the subject or may require medical or surgical intervention to prevent one of 
the outcomes listed in the above definition.  
Examples of important medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home; blood dyscrasias or convulsions that do not result in 
inpatient hospitalization; or the development of drug dependency or drug abuse. 
*Life threatening is defined as an AE or suspected adverse reaction that, in the view of either the 
investigator or sponsor, placed the subject at immediate risk of death as it occurred. It does not 
include an AE or suspected adverse reaction that, had it occurred in a more severe form, might 
have caused death. 

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All death events should be reported as the fatal outcome of an SAE, with the date and cause of 
death included. The medical event leading to the subject’s death (eg, respiratory failure, 
pneumonia) should be reported as the SAE term. If no alternative cause of death is identified, 
“progression of ALS” may be reported as the event term if deemed medically appropriate by the 
investigator.  
11.2.1.3.1. SAE Due to ALS 
Serious events (including events related to efficacy endpoints) that are considered ALS-related 
should be reported as “not related” SAEs. “ALS” or “disease progression” should not be reported 
as event terms if a more precise term for the complication or actual cause of hospitalization/death 
(eg, respiratory failure) can be reported.  
“Disease progression” is considered a worsening of a subject’s ALS symptoms (weakness, 
spasticity, respiratory insufficiency, respiratory arrest, dysphasia). It may reflect an increase in 
the severity of the disease or an increase in symptoms. 
Any event experienced by a subject which is solely regarded as part of disease progression and 
can be considered as a direct consequence of ALS, but does not result in death, should not be 
reported as an AE/SAE; examples include: respiratory insufficiency, dysphagia, respiratory 
failure, dysarthria, etc. However, if a subject should experience worsening of ALS-related 
disease symptoms that are not considered anticipated disease progression for that given subject, 
the investigator should report these findings as an AE. Examples of this might include: 
pneumonia, malnutrition, fall, or aspiration. If there is any uncertainty as to whether an event is 
due to anticipated disease progression, it should be reported as an AE. 
11.3. 
Relationship to Investigational Product 
The investigator will review each event and assess its relationship to investigational product 
treatment (not related, unlikely related, possibly related, or definitely related). The date and time 
of onset, time relationship to investigational product dosing, duration, and outcome 
(recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not recovered/not 
resolved, fatal, or unknown) of each event will be noted. 
Table 6 should be considered when evaluating the relationship of AEs/SAEs to study treatment. 
Table 6: 
Definitions of Adverse Event Relatedness 
Classification 
Definition 
DEFINITELY 
RELATED 
Strong evidence of a causal relationship; the influence of other factors is unlikely 
POSSIBLY 
RELATED 
Some evidence of a causal relationship, but other factors may have caused or contributed 
to the event (eg, another illness or concomitant treatment) 
UNLIKELY 
RELATED 
A causal relationship is not a reasonable possibility, but it cannot be completely ruled out 
with the available evidence. 
NOT 
RELATED 
No evidence of a causal relationship 

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11.4. 
Severity of Events 
The investigator will review each event and assess its severity. Note that severity is a measure of 
intensity, whereas seriousness is defined by the criteria in Section 11.2.1.2. An AE can be of 
severe intensity but not be considered serious. 
Table 7 presents the severity definitions that should be considered when evaluating the severity 
of AEs and SAEs.  
Table 7: 
Severity of Events 
Severity  
Definition/Description 
Mild 
Event results in mild or transient discomfort, not requiring intervention or treatment; 
does not limit or interfere with daily activities (eg, insomnia, mild headache). 
Moderate 
Event is sufficiently discomforting so as to limit or interfere with daily activities; may 
require interventional treatment (eg, febrile illness requiring oral medication). 
Severe 
Event results in significant symptoms that prevents normal daily activities; may require 
hospitalization or invasive intervention (eg, anemia resulting in blood transfusion). 
11.5. 
Recording Adverse Events 
Adverse events and SAEs will be collected from the signing of the informed consent form (ICF) 
until one of the following occurs: 
• follow-up (core) 
• follow-up (open-label) 
• follow-up (open-label, long-term extension) 
• early termination follow-up (ETFU) visit, 6 weeks after the last dose of 
pegcetacoplan.  
All SAEs will be followed until a final outcome of recovered, recovered with sequelae, or fatal, 
unless the subject withdraws consent or the investigator confirms that no additional information 
is available. 
All SAEs that are suspected of being related to study treatment must be reported immediately to 
the sponsor if the investigator becomes aware of them, regardless of the time since the 
completion of the clinical trial. 
Any events that occur prior to the start of dosing will be categorized as pretreatment events; 
events occurring after the start of dosing will be recorded as TEAEs (the start date of dosing and, 
therefore, categorization of the event will be dependent on randomization assignment). 
For each AE, the investigator will evaluate and report the onset date (and time if applicable), 
resolution date (and time, if applicable), intensity, causality, action taken, seriousness criteria 
met (if applicable), and whether or not the subject discontinued the study as a result of the event.  
If possible, the outcome of any AE resulting in permanent discontinuation or that was present at 
the end of the study should be reported, particularly if the AE was considered by the investigator 
to be related to the investigational product. Subjects experiencing AEs that cause interruption or 

Pe gcetac o pla n  
A P L 2 -A L S -2 0 6 Pr ot oc ol A me n d me nt 6  
1 3 Ja n uar y 2 0 2 3 
A pellis P har mace uticals, I nc  
Pa ge 8 5   
 
C o nfi de ntial  
disc o nti n uati o n of i n vesti gati o nal pr o d uct, or t h ose e x perie n ci n g A Es t hat are prese nt at t he 
f oll o w- u p (c or e)/f oll o w- u p ( o pe n-la b el)/f oll o w- u p ( o pe n-la b el, l o n g-ter m e xte nsi o n)/ E T F U visit 
s h o ul d recei ve f oll o w- u p as a p pr o priat e.  
All S A Es m ust be re p orte d t o t he s p o ns or/ A pellis Safet y via e C R F i m me di atel y, wit h o ut u n d ue 
dela y, u n der n o circ u mst a nces later t ha n 2 4 h o urs of bec o mi n g a w are of t he e ve nt, w het her or 
n ot t he e ve nt is dee me d treat me nt -r elate d. If t he el ectr o nic dat a ca pt ure ( E D C) s yste m is n ot 
o perati o nal ( or f or pa p er- base d st u dies), t he site m ust c o m plete t he pa per S A E f or m a n d e mail t o 
als o i m me diatel y, wit h o ut u n d ue dela y, u n der n o circ u msta nces later t ha n 
2 4 h o urs of bec o mi n g a w are of t h e e ve nt. T h e re p orte d i nf or mati o n s u b mitte d as a pa p er S A E 
m ust be e ntere d i nt o t he E D C s yste m o nce it bec o mes o perati o nal.  
A d verse e ve nts will be c o de d i n acc or da nce wit h t he Me dical Dicti o nar y f or Re g ulat or y 
Acti vities ( Me d D R A). If k n o w n, t he dia g n osis of t he u n derl yi n g ill ness or dis or der s h o ul d be 
rec or d e d, rat h er t ha n its i n di vi d ual s y m pt o ms. 
1 1. 6.  
Re p orti n g A d verse E ve nts  
T he s p o ns or has t he res p o nsi bilit y t o i nf or m c o ncer ne d healt h a ut h orities, et hic c o m mittees, 
a n d i n vesti gat ors a b o ut S U S A Rs i n li ne wit h G C P g ui da nce a n d a p plica ble re g ulat or y re q uire me nts.  
If re q uir e d, s pecific S A Es s h o ul d be re p orte d t o t h e c o ncer ne d et hic c o m mittees i n c o m plia nce 
wit h l ocal re q uire m e nts.  
1 1. 7.  
Pre g n a nc y  
Alt h o u g h pre g na nc y is n ot a n A E, all pre g n a ncies a n d s us pecte d pre g na n cies (i ncl u di n g a 
p ositi ve pre g na nc y test r e gar dless of a ge or diseas e state) occ urri n g wit h a fe male s u bject or t he 
fe male part ner of a male s u bject, m ust be f oll o we d t o c o ncl usi o n t o deter mi ne t heir o utc o me a n d 
are c o nsi d ere d i m me diat el y re p orta bl e e ve nts.  
A n y pre g na n c y, s us pect e d pre g na nc y, or p ositi ve pre g na nc y t est m ust be re p orte d t o 
A pellis  Safet y wit hi n 2 4 h o urs of t he I n vesti gat or bec o mi n g a ware of t h e e ve nt. Pre g na ncies 
s hall be re p orte d o n a Pre g na nc y Re p ort F or m, w hic h m ust be si g ne d a n d d ate d b y t he pri mar y 
i n vesti gat or a n d s u b mitte d via e mail t o 
 
T he i n vesti gat or m ust f oll o w t he s u bject u ntil c o m pleti o n of t he pre g na n c y a n d m ust re p ort t he 
o utc o me of t he pr e g na nc y (e g, deli ver y, t er mi nati o n, etc.) a n d n e o natal stat us u p t o 1 2 m o nt hs 
p ost deli ver y. A n a b n or m al o utc o me is defi ne d as t he birt h of a c hil d wit h p ersiste nt or si g nifica nt 
i nca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d uct n or mal life f u n cti o ns (f or merl y 
referre d t o as disa bilities), c o n ge nital a n o malies, or birt h defects. I n t he e v e nt of a n a b n or mal 
o utc o me, a n S A E m ust be re p ort e d usi n g t he S A E Re p ort F or m, as d escri b e d i n Secti o n  1 1. 4 . 
1 1. 7. 1.  
Acce pt a ble Met h o ds of C o ntr ace pti o n  
A p pr o ve d met h o ds of c o ntrace pti o n i ncl u de: 
•  C o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n: 
− oral, i ntra va gi nal, or tra ns der mal 
P P D
P P D

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• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
− oral, injectable, or implantable 
• Intrauterine device  
• Intrauterine hormone-releasing system  
• Bilateral tubal occlusion 
• Vasectomized partner (provided that partner is the sole sexual partner of the WOCBP 
trial participant and that the vasectomized partner has received medical assessment of 
the surgical success) 
• Sexual abstinence (defined as refraining from heterosexual intercourse during the 
entire period of risk associated with study treatments) 
• Male condom with or without spermicide (for male study subjects with female 
partners of childbearing potential only) 
Not all methods of contraception may be available in all of the countries in which the study is 
being conducted. 
Note: Sexual abstinence is only accepted when it is the preferred and usual lifestyle of the subject. 
Subjects must agree to use an approved method of contraception during the study and for 90 days 
after their last dose of investigational product.  
11.8. 
Abuse, Misuse, Overdose, and Medication Error 
Occurrences of events of drug abuse, drug misuse, drug overdose, and medication error must be 
reported to the sponsor. 
Abuse of a medicinal product: Persistent or sporadic, intentional, excessive use of medicinal 
products, which is accompanied by harmful physical or psychological effects. 
Misuse: Intentional and inappropriate use of a medicinal product not in accordance with the 
prescribed or authorized dose, route of administration, and/or intended indication(s), or not 
within the legal status of its supply. 
Overdose: Administration of a quantity of study drug per administration or per day, which is 
above the assigned dose. 
Medication Error: An error made in prescribing, dispensing, administration, and/or use of the 
study drug. Medication errors are reportable to the sponsor as defined below: 
• The dispensing, administration, and/or use of unassigned study drug. 
• The administration and/or use of an expired study drug. 
All AEs or SAEs associated with drug abuse, drug misuse, drug overdose, or medication error 
must be reported as appropriate. 

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12. 
STATISTICS 
A formal statistical analysis plan (SAP) will be developed and finalized prior to locking the 
database. The full details of data presentations and analyses will be provided in the SAP. 
Additional statistical analyses other than those described in this section may be performed if 
deemed appropriate and included in the SAP. Any deviations from the final SAP or from what is 
outlined in the protocol will be discussed in the final study report.  
12.1. 
Determination of Sample Size 
A sample size of 180 randomized subjects (2:1 allocation ratio to pegcetacoplan:placebo) would 
provide approximately 86% power to detect a significant difference (33%) in the primary 
outcome (CAFS score) between the 2 treatment groups at a 2-sided alpha of 5% with 75% power 
to detect a 35% improvement in the rate of decline in the ALSFRS-R score and 39% power to 
detect a 10% improvement in survival. 
The estimates were based on the following assumptions: 
• Mean monthly rate of decline in ALSFRS-R is 1 unit for the placebo treatment group 
and pooled standard deviation of 0.84 units/month 
• 52-week mortality rate with placebo at 20% 
• Approximately 40-week subject enrollment period 
• 52 weeks of follow-up for assessing survival outcomes after each subject enrolls  
• 52 weeks of follow-up for assessing functional outcomes after each subject enrolls 
Subjects will be randomized and stratified by location of first muscle weakness (limb or bulbar), 
riluzole and edaravone use. 
Approximately 228 subjects (152:76) will be randomized to account for an anticipated 20% of 
randomized subjects prematurely discontinuing the study without providing a postbaseline 
ALSFRS-R measurement. 
12.2. 
Analysis Set 
12.2.1. 
Screened Set 
The screened set will include all subjects who provide written informed consent. This set will be 
used only for the purpose of describing subject disposition. 
12.2.2. 
Safety Set 
The safety set will include all subjects who receive at least 1 dose of any double-blind 
investigational product. Subjects will be analyzed according to the treatment they received. 
12.2.3. 
Intent-to-Treat Set 
The intent-to-treat (ITT) set will include all randomized subjects who receive at least one dose of 
randomized treatment (pegcetacoplan or placebo). Subjects will be analyzed according to their 
assigned treatment, regardless of the treatment actually received.  

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12.2.4. 
Modified Intent-to-Treat Set 
The modified intent-to-treat (mITT) set will include all subjects in the ITT set who have at least 
1 postbaseline efficacy assessment. 
12.2.5. 
Per-Protocol Set 
The per-protocol (PP) set will include all subjects in the mITT set who have not violated any 
inclusion or exclusion criteria and/or deviated from the protocol in a way that could influence 
their efficacy assessment. Decisions concerning the exclusion of subjects from the PP analysis 
set will be made and documented prior to database lock. 
12.2.6. 
Pharmacokinetic Set 
The PK set will include all subjects in the safety set for whom the PK data are considered 
sufficient and interpretable.  
12.2.7. 
Pharmacodynamic Set 
The pharmacodynamic (PD) set will include all subjects in the safety set for whom the PD data 
are considered sufficient and interpretable.  
12.2.8. 
Data Review for Analysis Set 
After all the data have been verified/coded/entered into the database, a review will be performed. 
The purpose of this review will be to define the analysis populations. The review will also check 
the quality of the data, identifying outliers, and make decisions on how to deal with any data 
issues (eg, missing values, withdrawals, protocol deviations). After the preanalysis review, 
resolution of all issues and documentation of all decisions, the database will be locked. 
12.3. 
Efficacy Analysis 
12.3.1. 
Analysis of Primary Efficacy Endpoint 
The primary efficacy endpoint is the CAFS score at week 52.  
The CAFS score will be developed as follows: 
• The functional and survival outcomes are determined for every subject in the 
pegcetacoplan and placebo treatment groups. 
• All pairwise comparisons are performed and the scores of +1, 0, or –1 are assigned to 
a subject based on each pairwise comparison. The scores are assigned as follows: 
− If both subjects are deceased at the last point of contact, the subject with a longer 
survival receives a score of +1 and the other subject receives a score of –1. 
− If 1 subject is deceased and the other subject is alive at the last point of contact, 
the surviving subject receives a score of +1 and the deceased subject receives a 
score of –1. 

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− If both subjects are living at the last point of contact, the subject with a smaller 
change from baseline in the functional endpoint at the last point of contact 
receives a score of +1 and the other subject receives a score of –1.  
The scores from each pairwise comparison are added up for each subject. 
The CAFS ranks score will be summarized by treatment group using descriptive statistics. 
The CAFS ranks score will be analyzed using analysis of covariance (ANCOVA) model with 
treatment as a fixed effect, adjusted for baseline ALSFRS-R total score, duration from symptoms 
onset to the first dose of study treatment, and stratification factors. 
The primary efficacy analysis for the primary endpoint (CAFS) will be conducted on the mITT set 
and will be repeated for the PP set to evaluate the robustness of the results from the primary analysis. 
Other sensitivity analyses will be explored, and details will be provided in the SAP. 
12.3.2. 
Analysis of Secondary Efficacy Endpoints 
To preserve the Type 1 error, a fixed-sequence testing strategy will be used. The ordering of the 
secondary endpoints in this testing strategy will match the order in which they are presented in 
the secondary endpoint section.  
Absolute values and changes from baseline in secondary efficacy endpoints (ALSFRS-R, in-clinic 
percentage of predicted SVC, HHD, and ALSAQ-40) will be summarized, using descriptive 
statistics, by treatment and visit. Baseline will be taken as the measurement closest, but prior, to the 
first dose of investigational product. 
Changes from baseline in secondary efficacy outcomes (ALSFRS-R, in-clinic percentage of 
predicted SVC, HHD, and ALSAQ-40) will be summarized by treatment group and analyzed 
using a mixed model for repeated measures. The model will include fixed categorical effects for 
treatment, study visit, and the study visit-by-treatment interaction, as well as the continuous, 
fixed covariate of baseline and the visit-by-baseline interaction term, time from symptoms onset 
to the first dose of investigational product, and the randomization stratification factors. Initially 
an unstructured covariance matrix will be investigated. If this analysis fails to converge, other 
covariance structures will be used; details will be provided in the SAP. The Kenward-Roger 
approximation will be used to estimate denominator degrees of freedom. 
For the secondary endpoints of time to death and time to death, permanent tracheostomy, 
or permanent assisted ventilation, Kaplan-Meier analysis will be used to describe the survival 
data. The comparison of the survival time between treatment groups will be provided using a 
Cox proportional hazard model adjusting for the same covariates used in CAFS ANCOVA. 
For subjects who did not experience an event, the time to event will be censored at the last 
observation date for the Kaplan-Meier plot. Subjects who are lost to follow-up or who 
discontinued the study will be censored at the date of discontinuation or lost to follow-up date.  

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12.3.3. 
Analysis of Exploratory Efficacy Endpoints 
Absolute values and changes from baseline in exploratory endpoints will be summarized, using 
descriptive statistics, by treatment and visit: 
• EQ-5D-5L, ZBI, NfL, pNfH, and EIM at weeks 52, 104, and 156  
• At-home %SVC at week 52 and week 104 
• ALSFRS-R, %SVC (in-clinic), HHD, and ALSAQ-40 at week 156 
Baseline will be taken as the measurement closest to but prior to randomization. Time to 
percutaneous endoscopic gastrostomy tube placement up to weeks 52, 104, and 156 will be 
computed and summarized by treatment group, as will time to death, permanent tracheostomy, 
or permanent assisted ventilation up to week 156; and time to death up to week 156. Additional 
analyses might be performed for these endpoints and will be detailed in SAP. 
12.4. 
Safety Analysis 
All safety analyses will be summarized for the safety set. 
Adverse events will be coded using MedDRA. All AEs, including TEAEs, will be summarized 
by System Organ Class, Preferred Term, treatment group for number of subjects, and proportion 
reporting the event. A similar summary will be produced for SAEs, AEs leading to termination, 
severe AEs, and AEs related to the investigational product. The intensity of AEs and the 
relationship to investigational product will be summarized for each System Organ Class and 
Preferred Term by treatment group.  
Withdrawals due to AEs will be summarized for each body system and Preferred Term by 
treatment group. 
Treatment-emergent adverse events are defined as those AEs that develop or worsen after the 
first dose of study medication until the study follow-up visit or the ETFU visit.  
The AE summaries will be presented across all subjects. All AEs will be listed by subject, along 
with information regarding onset, duration, relationship, and severity to investigational product, 
action taken with investigational product, treatment of event, and outcome. In addition, 
the number and incidence of rejection episodes and graft loss will be tabulated. 
Laboratory assessment and anti–pegcetacoplan peptide antibody/anti-PEG antibody test results 
will be summarized by treatment group using appropriate descriptive statistics. 
Changes from baseline in clinical laboratory tests will be summarized, using descriptive 
statistics, by visit and nominal time postdose. Baseline will be taken as the measurement closest, 
but prior, to randomization. Out-of-range values will be flagged in data listings.  
Changes from baseline in vital signs will be summarized, using descriptive statistics, 
by treatment, visit, and nominal time postdose. Baseline will be taken as the measurement 
closest, but prior, to randomization. 
Values of potential clinical significance will be flagged in listings and summarized by treatment. 
Changes in physical examinations will be described in a data listing. 
Positive responses (Yes) to the C-SSRS will be summarized by treatment. 

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12.5. 
Pharmacokinetic Analysis 
The PK concentrations will be evaluated using the PK set. 
Concentrations will be summarized, using descriptive statistics, over time, in the randomized 
treatment group (pegcetacoplan group). 
Individual subject concentration-time data will be plotted against actual sampling time. 
Median profiles of the concentration-time data, using nominal sampling times, will also be 
presented. Both linear-linear and linear-log plots will be presented.  
12.6. 
Pharmacodynamic Analysis 
The PD endpoints will be evaluated using the PD set. 
Absolute values, changes from baseline, and percent changes from baseline will be summarized 
using descriptive statistics, over time by treatment group. 
Individual subject time profiles will be plotted against actual sampling time. Median profiles, 
over time, using nominal sampling time, will also be presented. 
The PD endpoints will be compared between treatment groups using mixed effect repeated 
measures analyses. 
12.7. 
Other Analyses 
Demographics, baseline characteristics, concomitant medication, medical history, and study 
medication exposure will be summarized by treatment group. 
World Health Organization and MedDRA coding dictionaries will be used for the concomitant 
medications and medical histories, respectively.  
12.8. 
Interim Analysis  
No interim analysis is planned. 
12.9. 
Data Monitoring Committee 
A DMC will review cumulative safety/tolerability data (eg, physical examinations, vital signs, 
clinical laboratory tests, and AEs). The DMC will also review data related to efficacy for the 
week 52 analysis and final analysis. The DMC will have the responsibility to conduct a thorough 
safety assessment at regular predefined intervals during the treatment period of the study. 
DMC meetings will be held according to the schedule in the DMC charter. An ad hoc DMC data 
review may be recommended by the DMC or requested by the sponsor at any time during the 
study. The first DMC meeting will be held after 20 subjects have completed visit 3 (week 4). 
The remit, roles, and responsibilities of the DMC will be specified in a separate DMC charter. 

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13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Before an investigational site can enter a subject into the study, a representative of the sponsor 
will contact the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) and other personnel their responsibilities with regard 
to protocol adherence, and the responsibilities of Apellis or its representatives. 
This will be documented in a Clinical Study Agreement between Apellis and the 
investigator. 
Subject information will be captured and managed by study sites on eCRFs by a web-based EDC 
tool developed and supported by the contract research organization (CRO) assisting with the conduct 
of the study and configured by the sponsor. It is recommended that data be entered into the EDC 
system within 5 business days, including batched records and records with source documents. 
Data management will be performed by the CRO according to their standard operating 
procedures. The data management plan will be approved by the sponsor. 
During the study, a monitor from Apellis or representative will have regular contacts with the 
investigational site, for, but not limited to, the following: 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm all participant data relating to the study will be recorded on printed or 
electronic case report form (CRF) unless transmitted to the sponsor or designee 
electronically (eg, laboratory data). The investigator is responsible for verifying that 
data entries are accurate and correct by physically or electronically signing the CRF. 
Any subject records or data sets that are transferred to the sponsor will contain the 
identifier only; subject names or any information which would make the subject 
identifiable will not be transferred.  
• Ensure that the investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 
• The sponsor/designee is responsible for the data management of this study, including 
quality checking of the data 
• Perform source data verification. This includes a comparison of the data in the case 
report forms with the subject’s medical records at the hospital or practice, and other 
records relevant to the study. This will require direct access to all original records for 
each subject (eg, clinic charts). Data reported on the CRF or entered in the eCRF that 
are transcribed from source documents must be consistent with the source documents 
or the discrepancies must be explained.  
• Record and report any protocol deviations not previously sent to Apellis. 

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• Confirm that AEs and SAEs have been properly documented on eCRFs and confirm 
any SAEs have been forwarded to Apellis and those SAEs that met criteria for 
reporting have been forwarded to the IRB/IEC. 
The monitor will be available between visits if the investigator(s) or other staff need(s) 
information or advice. 
13.1. 
Audits and Inspections 
Authorized representatives of Apellis, a regulatory authority, an IEC or IRB may visit the site to 
perform audits or inspections, including source data verification. The purpose of an Apellis audit or 
inspection is to systematically and independently examine all study-related activities and documents 
to determine whether these activities were conducted, and data were recorded, analyzed, 
and accurately reported according to the protocol, local laws, GCP guidelines of the International 
Council for Harmonisation, and any applicable regulatory requirements. The investigator should 
contact Apellis immediately if contacted by a regulatory agency about an inspection. 
13.2. 
Institutional Review Board/Independent Ethics Committee 
The principal investigator must obtain IRB/IEC approval for the investigational protocol. 
Initial IRB approval, and all materials approved by the IRB for this study including the subject 
consent form and recruitment materials must be maintained by the investigator and made 
available for inspection. 

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14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, Apellis, and/or 
authorized representatives of Apellis, may conduct a quality assurance audit(s) or pre–agency 
inspection visit(s). Please see Section 13.1 for more details regarding the audit process. 

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15. 
ETHICS 
15.1. 
Ethics Review 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC as appropriate. The investigator must submit 
written approval to Apellis before he/she can enroll any subject into the study. 
The principal investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements. In addition, the IRB or IEC must approve all 
advertising used to recruit subjects for the study. The protocol must be re-approved by the IRB 
or IEC upon receipt of amendments and annually, as local regulations require. 
The principal investigator is also responsible for providing the IRB with reports of any reportable 
serious adverse investigational product reactions from any other study conducted with the 
investigational product. Apellis will provide this information to the principal investigator. 
Progress reports and notifications of serious adverse investigational product reactions will be 
provided to the IRB or IEC according to local regulations and guidelines. 
15.2. 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and the Council for International Organizations of Medical 
Sciences International Ethical Guidelines 
• Applicable International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines 
• Applicable national laws and regulations 
15.3. 
Written Informed Consent 
The principal investigator(s) at each center will ensure that the subject is given full and adequate 
oral and written information about the nature, purpose, and possible risks and benefits of the 
study. Subjects must also be notified that they are free to discontinue from the study at any time. 
The subject is to be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The subjects must be informed that their personal study-related data will be used by the sponsor 
in accordance with local data protection laws. The level of disclosure must also be explained to 
the subject, who will be required to give consent for their data to be used as described in the 
informed consent. 
The subjects 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 
IRB/IEC members, and by inspectors from regulatory authorities. 

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The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures. The caregiver’s signed and dated informed consent must be obtained before 
conducting any caregiver-related study procedures. 
The principal investigator(s) must maintain the original, signed ICF. A copy of the signed ICF 
must be given to the subject and caregiver, respectively. 

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16. 
DATA HANDLING AND RECORDKEEPING 
16.1. 
Inspection of Records 
Apellis will be allowed to conduct site visits to the investigation facilities for the purpose of 
monitoring any aspect of the study. The investigator agrees to allow the monitor to inspect the 
investigational product storage area, investigational product stocks, investigational product 
accountability records, subject charts and study source documents, and other records relative to 
study conduct. 
16.2. 
Retention of Records 
The principal investigator must maintain all documentation relating to the study for a period of 
25 years end of the clinical trial. Medical files of subjects shall be archived in accordance with 
national law. If it becomes necessary for Apellis or the regulatory authority to review any 
documentation relating to the study, the investigator must permit access to such records. 

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17. 
PUBLICATION POLICY 
Both the use of data and the publication policy are detailed within the clinical study agreement. 
Intellectual property rights (and related matters), generated by the investigator and others 
performing the clinical study, will be subject to the terms of a clinical study agreement that will 
be agreed between the institution and the sponsor or its designee. With respect to such rights, 
the sponsor or its designee will solely own all rights and interests in any materials, data, and 
intellectual property rights developed by investigators and others performing the clinical study 
described in this protocol, subject to the terms of any such agreement. In order to facilitate such 
ownership, investigators will be required to assign all such inventions, either to their institution 
or directly to the sponsor or its designee, as will be set forth in the clinical study agreement. 

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Sta M, Sylva-Steenland R, Casula M, et al. Innate and adaptive immunity in amyotrophic 
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