Clinical trial NCT03226678
Conditions: Warm Autoimmune Hemolytic Anemia Cold Agglutinin Disease
Sponsor: Apellis Pharmaceuticals, Inc.
Start date: 2017-08-31; Completion date: 2022-09-12
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is to assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of APL-2 in subjects with warm Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD).

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: APL-2
Intervention descriptions: intervention 1: Complement (C3) Inhibitor

Protocol documents:
Prot_000.pdf: 







































































































































SAP_001.pdf: 
































































































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Part B Long Term Extension Statistical Analysis Plan 
Study Title: 
Protocol Number: 
Amendment  
Sponsor: 
Sponsor Contact: 
CRO: 
Version No./Date 
An Open Label, Prospective, Study to Assess the Safety, 
Tolerability, Efficacy and Pharmacokinetics of APL-2 in Patients 
with Warm Antibody Autoimmune Hemolytic Anemia (wAIHA) or 
Cold Agglutinin Disease (CAD)  
APL2-CP-AIHA-208  
Version 1.0 Amendment 4.0 / 17 Jan 2019 
Apellis Pharmaceuticals, Inc. 
100 5th Avenue, 3rd Floor 
Waltham, MA 02451 
 
Biostatistician 
E-mail:  
DP Clinical, Inc. 
9201 Corporate Boulevard, Suite 350 
Rockville, MD 20850, USA 
Telephone: 
 
Version 1.0 / 08 Nov 2022 
Confidential Statement: The information contained herein is proprietary and no part of this 
information may be reproduced, photocopied, stored on a retrieval system, or transmitted 
without the express written consent of Apellis Pharmaceuticals, Inc. and DP Clinical Inc. Any 
unauthorized use is prohibited. 
 
 
 
 
    
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
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Signatory Page 
 
This Statistical Analysis Plan was reviewed and approved by: 
 
 
Author 
 
 
 Biostatistics 
DP Clinical, Inc. 
Reviewer
 
 
 
, Biostatistics and Clinical Data Management 
DP Clinical, Inc. 
 
 
 
Date  
 
 
Approval 
 
 
  
Biostatistician (Contract) 
Apellis Pharmaceuticals, Inc. 
 
 
 
 
 
08-Nov-2022
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
 
 
 
 
Approval 
 
 
 
  
, Biostatistics 
Apellis Pharmaceuticals, Inc. 
 
 
 
 
 
 
Approval 
 
 
 
Apellis Pharmaceuticals, Inc. 
Date 
 
 
08-Nov-2022
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Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
 
TABLE OF CONTENTS  
 
Signatory Page .......................................................................................................................... 2 
1. 
List of abbreviations and acronyms .............................................................................. 8 
2. 
Introduction ................................................................................................................... 11 
3. 
Study Overview ............................................................................................................. 12 
3.1 
Study Objectives................................................................................................ 12 
3.2 
Study Endpoints ................................................................................................ 12 
3.2.1 
Primary Safety Endpoint ................................................................... 12 
3.2.2 
Efficacy Endpoints ............................................................................ 12 
3.2.3 
Exploratory Study Endpoints ............................................................ 13 
3.3 
Study Design ...................................................................................................... 13 
3.3.1 
Sample Size Considerations .............................................................. 16 
3.3.2 
Study Assessments Schedules ............................................................ 16 
4. 
General Considerations ................................................................................................ 17 
4.1 
Analysis Sets ...................................................................................................... 17 
4.2 
Definitions .......................................................................................................... 18 
4.2.1 
Study Day .......................................................................................... 18 
4.2.2 
Baseline and Change from Baseline ................................................. 18 
4.2.3 
Visit Windowing Based on Study Day ............................................... 20 
4.3 
Test Hypothesis and P-Value Justification ..................................................... 23 
4.4 
Procedures for Handling Missing Data and Dropouts .................................. 23 
4.4.1 
Safety Data ........................................................................................ 24 
4.4.2 
PK and Efficacy/PD Concentration Data ......................................... 24 
4.5 
Subgroup Analysis ............................................................................................ 25 
4.6 
Multi-Center Studies and Pooling of Centers ................................................ 25 
5. 
Statistical Analysis Methodology ................................................................................. 26 
5.1 
Study Subjects ................................................................................................... 26 
5.1.1 
Subject Disposition ........................................................................... 26 
5.1.2 
Protocol Deviations .......................................................................... 27 
5.1.3 
Demographics and Baseline Characteristics.................................... 29 
5.1.4 
Medical and Surgical History ........................................................... 30 
5.1.5 
Prior and Concomitant Medications ................................................ 31 
5.1.5.1 
Prior and Concomitant Derivations ............................... 31 
5.1.5.2 
Medication Listings ....................................................... 32 
5.1.5.3 
Medication Summary Tables ......................................... 32 
5.1.6 
Exposure ........................................................................................... 33 
5.1.6.1 
Compliance Derivations ................................................ 33 
5.1.6.2 
Exposure and Compliance Listings ............................... 34 
5.1.6.3 
Exposure and Compliance Summary Tables ................. 34 
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5.2 
Safety Analysis .................................................................................................. 34 
5.2.1 
Adverse Events .................................................................................. 35 
5.2.1.1 
Treatment-Emergent Adverse Events (TEAE) .............. 35 
5.2.1.2 
Treatment-Emergent Adverse Event Study Part ........... 35 
5.2.1.3 
Adverse Events of Special Interest and Special Search 
Categories 36 
5.2.1.4 
Time to Onset and Exposure Adjusted Incidence ......... 37 
5.2.1.5 
Adverse Event Listings ................................................. 38 
5.2.1.6 
Adverse Event Summary Tables ................................... 39 
5.2.2 
Clinical Laboratory Tests ................................................................. 41 
5.2.2.1 
Clinical Laboratory Normalization ............................... 41 
5.2.2.2 
Potentially Clinically Significant .................................. 42 
5.2.2.3 
Clinical Laboratory Listings .......................................... 43 
5.2.2.4 
Clinical Laboratory Summary Tables ........................... 44 
5.2.3 
Vital Signs ......................................................................................... 45 
5.2.3.1 
Potentially Clinically Significant .................................. 45 
5.2.3.2 
Vital Signs Listings ....................................................... 45 
5.2.3.3 
Vital Signs Summary Tables ......................................... 46 
5.2.4 
Electrocardiogram (ECG) ................................................................ 46 
5.2.5 
Physical Examination ....................................................................... 46 
5.3 
Exploratory Efficacy and Pharmacodynamic Analyses ................................ 46 
5.3.1 
Packed Red Blood Cell (PRBC) Transfusions .................................. 47 
5.3.1.1 
Transfusions Per Month ................................................ 47 
5.3.1.2 
Units Per Month ............................................................ 47 
5.3.1.3 
Transfusions Listings .................................................... 48 
5.3.1.4 
Transfusions Summary Tables ...................................... 49 
5.3.2 
Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue 
Scale 
49 
5.3.2.1 
FACIT Fatigue Score .................................................... 49 
5.3.2.2 
FACIT Listings .............................................................. 50 
5.3.2.3 
FACIT Summary Tables ............................................... 51 
5.3.2.4 
FACIT Summary Figures .............................................. 51 
5.3.3 
Linear Analog Self-Assessment (LASA) ............................................ 52 
5.3.3.1 
LASA Overall Quality of Life and Subscales ............... 52 
5.3.3.2 
LASA Listings ............................................................... 52 
5.3.3.3 
LASA Domain Summary Tables .................................. 53 
5.3.3.4 
LASA Domain Summary Figures ................................. 54 
5.3.4 
Efficacy Laboratory Parameters....................................................... 54 
5.3.4.1 
Parameters and Normalization ...................................... 54 
5.3.4.2 
Efficacy Laboratory Listings ......................................... 55 
5.3.4.3 
Efficacy Laboratory Summary Tables .......................... 55 
5.3.4.4 
Efficacy Laboratory Summary Figures ......................... 56 
5.3.5 
Pharmacodynamics ........................................................................... 57 
5.3.5.1 
Parameters ..................................................................... 57 
5.3.5.2 
PD Listings .................................................................... 58 
5.3.5.3 
PD Summary Tables ...................................................... 58 
5.3.5.4 
PD Summary Figures .................................................... 59 
5.3.6 
Anti-drug antibody Assay .................................................................. 59 
5.4 
Pharmacokinetic Analysis ................................................................................ 59 
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5.4.1 
Pharmacokinetic Concentration Summaries .................................... 59 
5.4.2 
Pharmacokinetic Parameters ............................................................ 61 
6. 
Testing/Quality Control Plan and Software/System .................................................. 62 
6.1 
Programming Specifications for TLFs............................................................ 62 
6.2 
Formatting Conventions ................................................................................... 62 
6.3 
Standard Text Conventions ............................................................................. 63 
6.3.1 
Header............................................................................................... 63 
6.3.2 
Title ................................................................................................... 63 
6.3.3 
Footnotes........................................................................................... 64 
6.3.4 
Footer ................................................................................................ 64 
6.4 
Statistical Conventions ..................................................................................... 65 
6.4.1 
Statistics Reported ............................................................................ 65 
6.4.2 
Tables Summarizing Categorical Data ............................................. 65 
6.4.3 
Subject Data Listings ........................................................................ 66 
7. 
References ...................................................................................................................... 67 
8. 
Appendices ..................................................................................................................... 68 
8.1 
Study Flow Charts ............................................................................................ 68 
8.2 
Planned Tables, Listings, and Figures ............................................................ 72 
 
 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
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1. LIST OF ABBREVIATIONS AND ACRONYMS 
 
Abbreviations and 
Acronyms 
Description 
°C 
Degrees Celsius  
ADaM 
Analysis Data Model 
ADDV 
ADaM Data Structure for Protocol Deviation Analysis 
ADPC 
ADaM Data Structure for Pharmacokinetic Concentrations 
Analysis 
ADPP 
ADaM Data Structure for Pharmacokinetic Parameters 
Analysis 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AIHA 
Autoimmune Hemolytic Anemia 
ATC 
Anatomical Therapeutic Chemical 
CAD 
Cold Agglutinin Disease 
BLQ 
Below the Limit of Quantification 
bpm 
beats per minute 
CFB 
Change From Baseline 
Ctrough, max 
Maximal Trough Concentration  
CS 
Clinically Significant Abnormality 
DPC 
DP Clinical Inc. 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
ET 
Early Termination 
ETFU 
Early Termination Follow-up 
FACIT 
Functional Assessment of Chronic Illness Therapy 
HiB 
Haemophilus Influenzae Type B 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use  
ITT 
Intent-to-Treat 
LASA 
Linear Analog Scale Assessment 
LDH 
Lactate Dehydrogenase 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
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Abbreviations and 
Acronyms 
Description 
LLOQ 
Lower Limit of Quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
mmHg 
Millimeters of Mercury 
msec 
Milliseconds 
NCS 
Not Clinically Significant  
ODS 
Output Delivery System 
QC 
Quality Control 
QoL 
Quality of Life 
PRBC 
Packed Red Blood Cell 
PCFB 
Percent Change From Baseline 
PCS 
Potentially Clinically Significant 
PCV13 
Pneumococcal Conjugate Vaccine 
PD 
Pharmacodynamics 
PI 
Principal Investigator or Designee 
PK 
Pharmacokinetics 
PP 
Per Protocol 
PPSV23 
Pneumococcal Polysaccharide Vaccine 23   
PT 
Preferred Term 
RBC 
Red Blood Cell 
RTF 
Rich Text Format 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TEAE 
Treatment-Emergent Adverse Event 
TLFs 
Tables, Listings and Figures 
wAIHA 
Warm Antibody Autoimmune Hemolytic Anemia 
WHO 
World Health Organization 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
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Abbreviations and 
Acronyms 
Description 
WHODrug 
World Health Organization Drug Dictionary 
WOCBP 
Woman of Childbearing Potential 
 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
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2. INTRODUCTION 
This Statistical Analysis Plan (SAP) is prepared to provide a more technical and detailed 
elaboration of the principal statistical features stated in the protocol. The SAP will ensure 
that the tables, listings, and figures that will be produced and statistical methods that will 
be used for the final analysis are complete and accurate and will allow valid conclusions 
to be drawn.  
 
In the development of this final analysis SAP, the following study documents were used: 
• Protocol Number (Version 1.0 Amendment 4), 17 Jan 2019 
• Electronic Case Report Form (eCRF), extracted 18 Oct 2021 
• Medical Coding Guidelines (Version 5.0), 10 Sep 2021 
 
The study protocol consists of two study parts for analysis (details of the scheduled 
assessments of the study parts can be found in Section 3.3 of the SAP): 
• Core Study Phase (Part A): the study period of the daily 270/280 mg or 360 mg 
APL-2 dose regimen.   
• Long Term Extension Phase (Part B): the study period of the twice or three times 
weekly 1080 mg APL-2 dose regimen.   
 
Statistical Analysis Plan Version 1.0 was used for the production of the Interim Part A 
Core Study Phase Analysis. This SAP will present the results for the final analysis for 
subjects who rolled over into Part B, presenting the safety and efficacy results of Part B 
and Part A + B as whole completed study as well. Definitions for the study days and 
baselines are outlined in Section 4. Details of the planned analyses are outlined in Section 
5. 
 
In the event that a discrepancy is found between the descriptions in the statistical section 
of the protocol and this document, the description in this document supersedes the 
descriptions in the statistical section of the protocol. Any deviations from the final analysis 
plan or from what is outlined in the protocol will be discussed in the final study report. 
 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
3. STUDY OVERVIEW 
This study is being conducted as part of a series of studies for the clinical development of 
APL-2. This study will be the initial exploration of APL-2 in patients with a primary 
diagnosis of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA) who relapsed 
from, did not respond to, or did not tolerate at least one prior wAIHA treatment regimen 
(such as prednisone, rituximab, or splenectomy), or a primary diagnosis of Cold 
Agglutinin Disease (CAD) regardless of prior treatment history. 
 
3.1 
Study Objectives 
The objectives of the study are to assess safety, tolerability, preliminary efficacy 
and pharmacokinetics (PK) of multiple subcutaneous (SC) doses of APL-2 in 
subjects with a primary diagnosis of wAIHA who relapsed from, did not 
respond to, or did not tolerate at least one prior wAIHA treatment regimen (such 
as prednisone, rituximab, or splenectomy), or a primary diagnosis of CAD 
regardless of prior treatment history. 
 
An exploratory objective of the study is to assess the pharmacodynamics (PD) 
of multiple SC doses of APL-2 when administered to wAIHA and CAD 
patients. 
 
3.2 
Study Endpoints 
3.2.1 Primary Safety Endpoint 
The primary safety endpoints of the study are the incidence and severity 
of 
Treatment-Emergent 
adverse 
events 
(TEAEs) 
following 
administration of multiple doses of SC APL-2. 
 
3.2.2 Efficacy Endpoints 
• Change from baseline in hemoglobin 
• Number of red blood cell (RBC) transfusions during the study 
• Change from baseline in absolute reticulocyte count 
• Change from baseline in lactate dehydrogenase (LDH) 
• Change from baseline in haptoglobin 
• Change from baseline in indirect bilirubin 
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Part B Long Term Extension Statistical Analysis Plan 
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• APL-2 serum concentrations and PK parameters, as appropriate 
• Change from baseline in Functional Assessment of Chronic Illness 
Therapy (FACIT) scale and the Linear Analog Scale Assessment 
scale (LASA) including energy level, ability to perform daily 
activity, and overall quality of life (QoL) 
 
3.2.3 Exploratory Study Endpoints 
Exploratory PD markers include: 
• Complement (e.g., CH50, AH50, and C3) activity and levels 
• C3 deposition on RBC cells 
 
3.3 
Study Design 
This is a Phase II, open-label, prospective pilot study of APL-2 conducted in 
subjects with a primary diagnosis of wAIHA or CAD in parallel. The study will 
consist of up to 24 subjects, a target of 12 subjects with a primary diagnosis of 
wAIHA in Cohort 1 and a target of 12 subjects with a primary diagnosis of CAD 
in Cohort 2. Subjects will be randomized 1:1 to a 270mg or 360mg daily SC APL-
2 dosage group within each cohort for up to 12 months (Part A, the Core Study 
Phase).  
 
Following Day 336 and the completion of the Part A Core Study Phase, subjects 
will be eligible to participate in Part B, a Long-Term Extension Phase, in order 
to continue to receive treatment with APL-2.  The Long-Term Extension Phase 
is described later in this section. 
 
Through Part A (Day 336), dose escalation from 270 mg/d to 360 mg/d, or de-
escalation from 360 mg/day to 270 mg/day may occur after a thorough evaluation 
of available safety and laboratory assessment. 
 
Safety will be assessed throughout the study; serial blood and urine samples will 
be collected for these assessments. Blood samples will be collected for the 
assessment of APL-2 PK. Additional samples for assessment of PD will also be 
collected. 
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Part B Long Term Extension Statistical Analysis Plan 
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Part A: Core Study Phase: 
Screening will take place within 30 days prior to the start of dosing on Day 1. If 
needed (see inclusion criteria), Neisseria meningitides types A, C, W, Y and B 
(administered as two separate vaccines), Pneumococcal Conjugate Vaccine 
(PCV13) or Pneumococcal Polysaccharide Vaccine 23 (PPSV23), and 
Haemophilus Influenzae Type B (Hib) vaccinations will be administered prior to 
dosing on Day 1. 
 
Subjects who meet all the inclusion criteria and none of the exclusion criteria will 
be enrolled into the study on Day 1 at a time designated by the Principal 
Investigator or designee (PI). During study, the first 3 daily SC doses of APL-2 
(Day 1 to 3) as well as doses on Day 7 and Day 14 will be administered at the 
clinical site. From Day 4 to Day 336 daily doses of APL-2 will be administered 
off-site by a study nurse or self-administered by the subject and/or caregiver, at 
the subject’s home, workplace, or other location convenient to the subject with 
the exception of those days where dosing is at the clinical site. At any time during 
the study, if subjects discontinue treatment, or if after the conclusion of the Part 
A Core Study Phase a subject does not elect to enter the Part B Long-Term 
Extension Phase, subjects will return to the clinical site for safety follow-up study 
procedures after 6 weeks, followed by final study procedures at an Exit Visit after 
another 6 weeks. See Study Flowchart in Section 3.3.2. 
 
The planned length of participation in the study for each subject is at least 
approximately 450 days (from Day –30 through completion of the Day 420 Exit 
visit procedures [for subjects that do not elect to enter the Part B Long-Term 
Extension Phase]). Subjects that continue in the Part B Long-Term Extension 
Phase may continue to receive treatment indefinitely until the subject 
discontinues or the development program is terminated. The study duration may 
change in the event that the study is terminated early, additional subjects are 
needed, additional time is required to review safety between groups, or extended 
safety and PK sampling is added for a dose group (e.g. beyond Day 420). 
 
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Part B: Long-Term Extension Phase: 
Following Visit 15 (Week 48), subjects who elect to continue in the Part B Long-
Term Extension Phase will return to the site at 12-week intervals indefinitely until 
the subject discontinues or the development program is terminated. 
 
Specific procedures for each visit are listed in the Study Flow Chart for the Long-
Term Extension Phase in Table 2 in Section 3.3.2.  
 
At Visit 15 (Week 48), subjects electing to enter the Part B Long-Term Extension 
Phase will begin an APL-2 dose regimen of APL-2 1,080 mg twice weekly (with 
potential to escalate to APL-2 1,080 mg every 3 days). When switching from the 
Part A Core Study Phase formulation and dose of APL-2 (270 mg/d or 360 mg/d) 
to the formulation and dose intended for use in the Long-Term Extension Phase 
(APL-2 1,080 mg twice weekly), subjects should return to the site for APL-2 
administration training and to conduct Dose Transition Visits 1, 2 and 4 weeks 
after the new dose is initiated and perform the procedures outlined in Appendix 
Section 8.1.  
 
Subjects who plan on continuing in the Part B Long-Term Extension Phase 
should be instructed to skip their daily Part A Core Study Phase Dose the day 
prior to Visit 15 (i.e., the subject should not self-administer APL-2 on Day 335).  
 
Note: The first dose of APL-2 1,080 mg should be administered at the Visit 15 
(Day 336), with Dose Transition Visits at Week 49, Week 50, and Week 52. Some 
subjects may enter the Part B Long-Term Extension Phase prior to the availability 
of the sorbitol formulation. These subjects should continue on their Part A Core 
Study Phase dose into the Part B Long-Term Extension Phase. These subjects 
will transition to the Long-Term Extension Phase dose at the next scheduled visit 
at which the sorbitol formulation and dose is available, and should schedule Visits 
T1, T2, and T3 1, 2 and 4 weeks following the visit at which the sorbitol dose is 
initiated. These subjects should be instructed to skip their Part A dose the day 
before the visit at which the APL-2 1,080 mg twice weekly dose regimen is 
scheduled to be initiated. 
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Subjects who discontinue treatment early should complete one Early Termination 
Follow-up Visit (ETFU) 6 weeks after discontinuation of treatment, and one 
Early Termination (ET) Exit Visit 6 weeks after the ETFU as outlined in 
Appendix 8.1.   
 
Study Assessments that align with those conducted in the Core Study Phase and 
are described in Section 13 of the Clinical Study Protocol and assessments that 
align with those conducted in the Long-Term Extension Phase are described in 
Section 17.3.2 of the Clinical Study Protocol (Version 1.0 Amendment 4), 17 Jan 
2019.    
 
3.3.1 Sample Size Considerations  
As this is a pilot study the sample size is not based on formal statistical 
testing. The sample size is considered sufficient to obtain useful safety, 
tolerability, PD, and PK data to assist the planning of future studies. 
 
3.3.2 Study Assessments Schedules   
Study assessments are described in detail in Section 12.0 of the 
protocol (Version 1.0 Amendment 4) and summarized in Study Flow 
Charts for Part A and Part B in Appendix Section 8.1.  
 
 
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4. GENERAL CONSIDERATIONS  
4.1 
Analysis Sets  
After all the data have been verified/coded/entered into the database, a review 
will be performed by DP Clinical, Inc (DPC) and the sponsor. The purpose of this 
review will be to define the analysis sets. The review will also check the quality 
of the data, identifying outliers, and making decisions on how to deal with 
problems in any data (e.g., missing values, withdrawals, protocol deviations). 
After the pre-analysis review, resolution of all issues and documentation of all 
decisions, the database will be locked. 
 
All Enrolled Subjects: 
All Enrolled Subjects will include all subjects that signed an informed consent 
during the Screening Period prior to Part A. All Enrolled Subjects will be used 
only for summaries of disposition from Part A through Part B and the end of 
study.  
 
Safety Set / Intent-to-Treat (ITT) / Pharmacodynamic (PD) Set: 
Safety Set will only include the subjects who roll over to Part B and receive at 
least one dose of 1080 mg APL-2.  
 
ITT Set and PD Set will be identical to the Safety Set for this study.  
 
Per Protocol (PP) Set: 
PP Set will only include subjects who were in the PP set in Part A and roll over 
to Part B and have not violated any inclusion or exclusion criteria and/or deviated 
from the protocol in a way that could influence their efficacy assessment while 
on study in Part B.  
 
The PP Set will be used in efficacy analyses for Part B and Part A + B.  
 
Decisions concerning the exclusion of subjects from the PP sets will be made and 
documented during an adjudication by DPC and the sponsor prior to database 
lock.  
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Pharmacokinetic (PK) Set:  
The PK Set will only include all subjects in the Safety Set who rolled over into 
Part B and have at least one evaluable non-BLQ post-dose PK measurement. 
 
4.2 
Definitions  
4.2.1 Study Day  
Part A + B: 
Study Day 1 for Part A + B will be the day a subject takes the first dose 
of APL-2, which will be calculated as: 
 
For events that occurred on the day of or after administration of 
the first APL-2 dose: 
Part A + B Study Day = visit date – date of first APL-2 dose + 1 
 
For events that occurred on days before administration of the 
first APL-2 dose: 
 
 
    
Part A + B Study Day = visit date – date of first APL-2 dose 
 
Part B: 
Part B is considered all visits and assessments from the date of first 1080 
mg APL-2 dose through the date of last APL-2 dose.  
 
For events that occurred on the day of or after administration of the first 
1080 mg APL-2 dose in Part B Long Term Extension Phase: 
 
   Part B Study Day = visit date – date of first 1080 mg APL-2 dose + 1 
 
For events that occurred on days before administration of the first 1080 
mg APL-2 dose: 
 
 
   Part B Study Day = visit date – date of first 1080 mg APL-2 dose 
 
4.2.2 Baseline and Change from Baseline  
Summary tables will present: 1) change from Part A  baseline summaries 
assessments during Part A + B and 2) change from Part B baseline 
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summaries assessments during Part B. This section outlines the 
definitions for baseline and change from baseline for all safety and 
efficacy assessments collected during study visits, except for 
transfusions (see Section 5.3.1). 
 
Part A + B 
The baseline for Part A + B summaries will be the Part A Baseline. 
Unless indicated otherwise Change from Part A+ B Baseline (Part A + 
B CFB) will be calculated as follows: 
Part A + B CFB = Visit Result –  
Part A Baseline Result 
 
Percent Change from Part A + B Baseline (Part A + B PCFB) will be 
calculated as follows: 
Part A + B PCFB (%) = 100*(Visit Result – Part A Baseline Result)/
 
(Part A Baseline Result), 
 
where Part A baseline is the last assessment prior to the first APL-2 dose 
in Part A. 
 
Part B 
Part B baseline for this study will be derived as the last measure prior to 
the first 1080 mg APL-2 dose.  
 
Unless indicated otherwise Part B change from baseline (Part B CFB) 
will be calculated as follows for after Part B Study Day 1: 
Part B CFB = Visit Result – Part B Baseline Result 
 
Percent change from baseline (Part B PCFB) will be calculated as 
follows: 
Part B PCFB (%) = 100*(Visit Result – Part B Baseline Result)/ 
  
(Part B Baseline Result) 
 
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Part A Visit 6 (Week 2) 
Part A+B Study 
Day 14 
11– < 21 
10 
Part A Visit 7 (Week 4) 
Part A+B Study 
Day 28 
21- < 42 
21 
Part A Visit 8 (Week 8) 
Part A+B Study 
Day 56 
42 - <70 
28 
Part A Visit 9 (Week 12) 
Part A+B Study 
Day 84 
70 - < 98 
28 
Part A Visit 10 (Week 16) 
Part A+B Study 
Day 112 
98 - < 126 
28 
Part A + B, 
cont. 
Part A Visit 11 (Week 20) 
Part A+B Study 
Day 140 
126 - < 154 
28 
  
Part A Visit 12 (Week 24) 
Part A+B Study 
Day 168 
154 - < 196 
42 
  
Part A Visit 13 (Week 32) 
Part A+B Study 
Day 224 
196 - < 252 
56 
  
Part A Visit 14 (Week 40) 
Part A+B Study 
Day 280 
252 - < 308 
56 
  
Part A Visit 15 (Week 48) 
Part A+B Study 
Day 336 
308 - < 378 
70 
  
Part A Visit 16 (Week 60) 
Part A+B  Study 
Day 420 
378 - < 462 
84   
  
Part A Visit 17 (Week 72)    
Part A+B  Study 
Day 504 
462 - < 546 
84 
  
Subjects who had assessments at Part A Visit 16/17 are included in safety summaries but 
not efficacy summaries. 
  
Part B Baseline (Day 1) 
Date of First 
1080 mg Dose = 
Part B Study 
Day 1 
≤ Part B Study Day 1* 
NA 
Part B Transition Visit 1  
(Day 7) 
Part B Study 
Day 7 
> Part B Study Day 3 -  
< Part B Study Day 11 
7 
Part B Transition Visit 2 
(Week 2) 
Part B Study 
Day 14 
Part B Study Day 11 -  
< Part B Study Day 21 
10 
Part B Transition Visit 3 
(Week 4) 
Part B Study 
Day 28 
Part B Study Day 21 -  
< Part B Study Day 56 
25 
  
Part B Visit 1 (Week 12) 
Part B Study 
Day 84 
Part B Study Day 56 - 
Part B Study Day < 126 
70 
  
Part B Visit 2 (Week 24) 
Part B Study 
Day 168 
Part B Study Day 126 - 
Part B Study Day < 210 
84 
  
Part B Visit 3 (Week 36) 
Part B Study 
Day 252 
Part B Study Day 210 - 
Part B Study Day < 294 
84 
  
Part B Visit 4 (Week 48) 
Part B Study 
Day 336 
Part B Study Day 294 - 
Part B Study Day < 378 
84 
  
Part B Visit 5 (Week 60) 
Part B Study 
Day 420 
Part B Study Day 378 - 
Part B Study Day < 462 
84 
  
Part B Visit 6 (Week 72) 
Part B Study 
Day 504 
Part B Study Day 462 - 
Part B Study Day < 546 
84 
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4.4.1 Safety Data 
Where appropriate, screening values may be used as baseline in the event of 
missing or unusable Day 1 measurements. No imputation of missing data for 
early terminations will be performed.  
 
However, both partial and completely missing dates/times that are not related 
to early terminations, in addition to missing safety data (e.g., missing severities) 
will be reviewed on a case-by-case basis for potential imputations. As a general 
rule, a conservative approach will be adopted as outlined in Section 5.2.1 (e.g. 
partial Adverse Event (AE) onset dates and missing severities will be taken as 
the earliest ‘on treatment’ start date and highest severity, respectively, 
consistent with the partial information available).   Moreover, the original data, 
without imputations, will be presented separately in data listings.  
 
For safety lab parameters that are below or above the limit of quantification, the 
data will be presented as-is in the listings, but the limit of quantification will be 
used for the purposes of calculating change from baseline. 
 
4.4.2 PK and Efficacy/PD Concentration Data 
APL-2 concentrations reported from pre-dose on Day 1 to the time of the first 
quantifiable value will be taken as zero for linear plots and the calculation of 
PK parameters, and equal to the lower limit of quantification (LLOQ) for semi-
logarithmic plots.  
 
After this time point, concentrations below the limit of quantification (BLQ) 
will be set to zero, with the exception of the calculation of the geometric mean 
where the LLOQ will be used.  
 
If a BLQ value falls between two quantifiable concentrations the value will be 
set equal to the LLOQ, unless its exclusion can be justified (e.g. implausibility 
given the profile observed and known PK properties).  
 
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In the event of a missing PD baseline value a screen measurement or pre-dose 
unscheduled measurement may be used (whichever is closer to the baseline 
date). 
 
If a baseline PD value is zero, then the percent change from baseline will not be 
calculated. If a post baseline value is BLQ, then the value will be set to the 
LLOQ. Similarly, for PD plots, a BLQ value will be set equal to LLOQ. 
 
4.5 
Subgroup Analysis 
Due to the small sample size of the study, no subgroup analyses will occur. 
 
4.6 
Multi-Center Studies and Pooling of Centers 
This is a multi-center study. Due to the small number of subjects at each site, no 
adjustments will be made for study site. 
 
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5. STATISTICAL ANALYSIS METHODOLOGY  
In general, tables will be presented by cohort (Cohort 1 wAIHA / Cohort 2 CAD) and 
study part (Part A + B / Part B). The Part B summaries will start from Study Day 1 in Part 
B  through the end of the Part B Long Term Extension Phase, while Part A + B will start 
from Study Day 1 in Part A through the end of the Part B Long Term Extension Phase.  
 
Tabulations for continuous data will use a standard set of descriptive statistics for the 
results and for change from baseline, as specified: number of observations available (n), 
mean, standard deviation (SD), median, and range (minimum, maximum). Change from 
Baseline for Part A + B summaries will calculate the  Change from Part A Baseline 
summary statistics. Change from Baseline for Part B summaries will calculate the  Change 
from Part B Baseline summary statistics.  
 
Categorical or dichotomous data will be tabulated using frequencies (counts and 
percentages). The numerator and denominator for each percentage calculation will be 
specified in the footnotes of table shells.   Categorical data will be populated as appropriate 
for each study part (Part A + B and Part B). 
 
Data listings will present all information recorded in eCRFs for all subjects and visits. All 
listings will be sorted by cohort and subject number.  
 
5.1 
Study Subjects 
5.1.1 Subject Disposition  
The subject disposition will summarize All Enrolled Subjects from 
Screening prior to Part A through the end of Part B. The following 
disposition categories will be tabulated by cohort (Cohort 1 wAIHA / 
Cohort 2 CAD): 
o Number of subjects screened 
o Screen Failure Reasons 
o Number of subjects who discontinued prior to the first dose 
of APL-2 
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o Number of subjects who receive at least at least one dose of 
APL-2 in Part A phase (Safety Set in Part A Core Study 
Phase) 
o Number of subjects who completed treatment phase through 
Visit 15   
o Number of subjects in the Part A PP Set  
o Number of early termination subjects during Part A Core 
Study Phase with reason for early termination  
o Number of subjects who discontinued after Part A 
completion and prior to Part B with reason for termination 
o Number of subjects who receive at least one 1080 mg APL-
2 dose in Part B phase (Safety/ITT/PD Set) 
o Number of subjects in Per Protocol set per definition in 
Section 4.2 
o Number of subjects in PK set  
o Reason for Withdrawal during Part B Long Term Extension 
Phase  
 
5.1.2 Protocol Deviations 
A protocol deviation is any change, divergence, or departure from the 
study design or procedure defined in the protocol.  
 
The following categories will be used to group protocol deviations: 
1. 
Eligibility Not Met 
2. 
Study Assessment Noncompliance 
3. 
Study Drug Noncompliance 
4. 
Study Schedule Noncompliance 
5. 
Other 
 
The following are categorical reasons used to document why a protocol 
deviation occurred: 
1. 
Subject Illness 
2. 
Subject Unable to Comply 
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3. 
Subject Refusal 
4. 
Clinical/Site Error 
5. 
Laboratory Error 
6. 
Investigator/Staff decision 
7. 
Other   
 
Subsets of the protocol deviations can be identified as major and minor 
protocol deviation as described below: 
 
Major Protocol Deviation: A protocol deviation that might significantly 
affect the completeness, accuracy, and/or reliability of the study data or 
that might significantly affect a subject’s rights, safety, or well-being.    
 
Minor Protocol Deviation: A protocol deviation that will not 
significantly affect the completeness, accuracy, and/or reliability of the 
study data and that will not significantly affect a subject’s rights, safety, 
or well-being.  
 
Upon soft lock of database, all documented protocol deviations in the 
study will be reviewed to identify all major and minor protocol 
deviations by a data review team including representatives from DPC 
clinical operations, medical, data management, and statistics, and sent 
to the sponsor for approval. Final decisions will be documented in the 
eTMF and incorporated into the CDISC datasets (SDTM DV and ADaM 
ADDV).  
 
All protocol deviations will be listed. A separate listing will include only 
the major protocol deviations.  
 
The following protocol deviation summaries will be tabulated by cohort 
(Cohort 1 wAIHA / Cohort 2 CAD) for Part A + B and Part B. The study 
part will be determined by the protocol deviation start date, i.e. protocol 
deviations that began at any point during Part A or Part B will be 
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summarized in Part A + B and protocol deviations that began on or after 
the date of first 1080 mg APL-2 dose (Part B Study Day 1) will be 
summarized in Part B.    
• Part A + B: 
o The number of deviations and number/proportion of 
subjects with protocol deviations during Part A + B and 
with major protocol deviations during Part A + B.  
o The number of deviations and number/proportion of 
subjects with each protocol deviation category during 
Part A + B.   
• Part B: 
o The number of deviations and number/proportion of 
subjects with protocol deviations during Part B and with 
major protocol deviations during Part B.  
o The number of deviations and number/proportion of 
subjects with each protocol deviation category during 
Part B.   
 
5.1.3 Demographics and Baseline Characteristics 
The following demographics will be tabulated by cohort (Cohort 1 
wAIHA / Cohort 2 CAD) using summary statistics for continuous 
parameters and frequency/percent for categorical parameters at Part A 
Core Study Phase Baseline for Safety/PP Analysis Set:  
• Age 
• Sex 
• Race 
• Ethnicity 
• Baseline Height 
• Baseline Weight 
• Baseline BMI 
 
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The following baseline characteristics will be tabulated using summary 
statistics for continuous parameters and frequency/percent for 
categorical parameters as well: 
• Time since diagnosis of wAIHA or CAD 
• CH50 
• AH50 
• Complement C3 
• C3d Type I, Type II, Type III 
• Reticulocytes 
• Haptoglobin 
• Hemoglobin 
• Anaemia categories (Mild: Hemoglobin ≥ 10 / Moderate: 5 ≤ 
Hemoglobin < 10 / Severe: Hemoglobin < 8) 
• Plasma Hemoglobin 
• Direct Antiglobulin Test (Negative / Positive) 
• Baseline Cold Agglutinins (< 1:32 / 1:128 / 1:256 / 1:512 / > 
1:512) 
• Anti-C3 Coombs (Negative / WKPOS / 1+POS / 2+POS / 
3+POS / 4+POS) 
• Number of Transfusions Per Month in 12 Months Prior to First 
Dose (derived as the number of Packed Red Blood Cell 
transfusions in the 365 days prior to first APL-2 dose*365/28) 
 
5.1.4 Medical and Surgical History 
Medical and Surgical history was collected at Screening. All 
medical/surgical history data and ongoing medical history will be listed 
and summarized at Part A + B Baseline for the Safety and PP Analysis 
Sets by the Medical Dictionary for Regulatory Activities (MedDRA) 
version 23.0 System Organ Class (SOC) and Preferred Term (PT) and 
by cohort (wAIHA / CAD).  
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5.1.5 Prior and Concomitant Medications 
5.1.5.1 
Prior and Concomitant Derivations 
Prior and concomitant medications will be coded to the therapeutic drug 
classes and generic drug names using the World Health Organization 
(WHO) Drug Dictionary (WHODrug) classifications version March 
2021. 
 
Prior medications will include any medications reported with a start date 
prior to the subject taking their first study dose of Part A Core Study and 
will be summarized by WHODrug Anatomical Therapeutic Chemical 
(ATC) Class 3 Term and WHODrug Preferred Name.  
 
Concomitant medications (CM) will include any medications being 
taken after the subject starts their study medication and will also be 
summarized by WHODrug ATC Class 3 Term and WHODrug Preferred 
Name.  Hence, medications ongoing at the start of dosing will be 
counted in both the prior and concomitant medication summaries.    
Further categorization for concomitant medications will be included in 
the analysis: 
• Part A + B CM: Any medication taken during Part A or Part B of 
the study. This can include prior medications that were continued 
into Part A and Part B of the study 
• Part B CM: Any medication taken during Part B of the study. This 
can include prior medications that were taken continuously into Part 
B of the study. Concomitant medications taken in Part A but ended 
prior to Part B will not be considered as concomitant medications 
during Part B. 
 
For the purposes of determining prior/concomitant medications and 
study part, if a partial date is recorded, the following convention will be 
used to assign the medication dates:  
• If a start date is missing the day information and month/year is the 
same as first dose date then use first dose date, else ‘01’ will be used 
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for the day; if a start date is missing the month and the year is the 
same as first dose date then use first dose date, else January will be 
used for the start month. 
• If a stop date is missing the day information and month/year is same 
as last study date then use last study date, else last day of the given 
month will be used for the stop day; if a stop date is missing the 
month and year is the same as last study date then use last study date, 
else December will be used for the stop month. 
 
5.1.5.2 
Medication Listings 
All prior medications and concomitant medications, interventions and 
procedures will be presented in listings for all subjects in Safety Set.  
 
The categorization of concomitant medications (CM Part A + B / CM 
Part B) will be included in the listings. 
 
5.1.5.3 
Medication Summary Tables 
The following summaries will be tabulated:  
• Prior Medications, subjects who had medications prior to entering 
Part A Core Study Phase in the Safety Set:  
o Frequency of subjects taking prior medications by 
WHODrug ATC Class 3 and Preferred Name, and by cohort 
• Concomitant Medications: 
o Part A + B: 
▪ For concomitant medications taken during Part A or 
Part B: Frequency of subjects by concomitant 
medication WHODrug ATC Class 3, Preferred 
Name, and by cohort  
o Part B: 
▪ Frequency of subjects by concomitant medication 
WHODrug ATC Class 3, Preferred Name, and by 
cohort  
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5.1.6 Exposure 
All study drug exposure data will be listed based on the Study Drug 
Administration eCRF.    
 
5.1.6.1 
Compliance Derivations 
The compliance for Part A + B must incorporate the different dosing 
regimens of the daily APL-2 dosing regimen (Part A) and the twice/three 
times weekly APL-2 dosing regimen (Part B).  
 
Part A Compliance 
For Part A, compliance will be calculated as: 
 
                   𝑃𝑎𝑟𝑡 𝐴 𝐶𝑜𝑚𝑝𝑙𝑖𝑎𝑛𝑐𝑒= 
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑒 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 
 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐴
𝑡𝑜𝑡𝑎𝑙 𝑒𝑥𝑝𝑒𝑐𝑡𝑒𝑑 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐴𝑥 100 
 
Unless otherwise noted, during the Part A Core Study Phase, the number 
of expected doses is the number of days during Part A for subjects that 
did not roll over into Part B. For subjects that rolled over into Part B, the 
expected number of doses is the number of days during Part A – 1 to 
account for the skipped dose prior to the dose transition 
 
Part B Compliance 
For the Part B, compliance will be calculated as: 
        𝑃𝑎𝑟𝑡 𝐵 𝐶𝑜𝑚𝑝𝑙𝑖𝑎𝑛𝑐𝑒= 
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑒 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑
𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐵 𝑝𝑟𝑖𝑜𝑟 𝑡𝑜 𝑠𝑡𝑢𝑑𝑦 𝑑𝑖𝑠𝑐𝑜𝑛𝑡𝑖𝑛𝑢𝑎𝑡𝑖𝑜𝑛/𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑖𝑜𝑛
𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑒𝑥𝑝𝑒𝑐𝑡𝑒𝑑 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐵
𝑥 100 
 
That is, when subjects receive twice weekly dosage, percentage 
compliance will be calculated as: 
𝑃𝑎𝑟𝑡 𝐵 𝐶𝑜𝑚𝑝𝑙𝑖𝑎𝑛𝑐𝑒= 
𝑎𝑐𝑡𝑢𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑒 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑
(last dose date −first dose date + 3.5)/7) x 2
𝑥 100 
Pegcetacoplan (APL-2) 
 
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When subjects receive every 3 days dosage, percentage compliance will 
be calculated as: 
𝑃𝑎𝑟𝑡 𝐵 𝐶𝑜𝑚𝑝𝑙𝑖𝑎𝑛𝑐𝑒= 
𝑎𝑐𝑡𝑢𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑒 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑
last dose date −first dose date
3
+ 1
𝑥 100 
 
Part A + B Compliance 
Using the above, the compliance during Part A + B period will be 
calculated as: 
        𝑃𝑎𝑟𝑡 𝐴 +  𝐵 𝐶𝑜𝑚𝑝𝑙𝑖𝑎𝑛𝑐𝑒= 
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑒 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑
 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐴
+ 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑒 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 𝑎𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑
𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐵
𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑒𝑥𝑝𝑒𝑐𝑡𝑒𝑑 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐴+ 𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑒𝑥𝑝𝑒𝑐𝑡𝑒𝑑 𝑠𝑡𝑢𝑑𝑦 𝑑𝑜𝑠𝑒𝑠 𝑑𝑟𝑢𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐵𝑥 100 
 
5.1.6.2 
Exposure and Compliance Listings 
All APL-2 Study Drug administration and Drug accountability will be 
listed. Compliance during Part A + B and Part B will be listed by subject.  
 
5.1.6.3 
Exposure and Compliance Summary Tables 
The following exposure and compliance parameters will be summarized 
by Part A + B and Part B and cohort (Cohort 1 wAIHA / Cohort 2 CAD): 
• Total dose administered summary statistics 
• Duration (total dosing period in days) summary statistics 
• Compliance summary statistics 
• Compliance frequency categories (Compliance < 80% / 80% ≤ 
Compliance < 90% / 90% ≤ Compliance < 100% / 100% ≤ 
Compliance < 120% 
 
5.2 Safety Analysis 
The primary objective of the study is to assess the safety and tolerability of APL-
2. The safety analyses will be performed on Safety Set per the specifications 
outlined in the subsections below. 
 
Pegcetacoplan (APL-2) 
 
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5.2.1 Adverse Events 
5.2.1.1 Treatment-Emergent Adverse Events (TEAE) 
TEAEs are defined as those AEs that occur after Dosing on Day 1, or worsen in 
severity, and up to 8 weeks (56 days) after the last dose of APL-2.  
 
AEs will be considered Treatment-Emergent (TEAE) unless there is clear 
indication that the event occurred prior to first dose of study drug.  AEs present 
prior to the first dose of study drug administration that increased in severity or 
relationship to study drug after the first dose of study drug and up to 56 days 
beyond the last dose of study drug will be classed as a TEAE.  Events with 
missing or partial dates will be handled such that in the absence of contradictory 
information an AE is Treatment-Emergent.  So, for a missing start date (where 
stop date is after date of first dose) the date will be imputed as the date of first 
dose; for a missing stop date the date will be imputed as the last study date.  If 
a partial date is recorded, the following convention will be used to assign the 
AE:  
• If a start date is missing the day information and month/year is the 
same as first dose date then use first dose date, else ‘01’ will be used 
for the day; if a start date is missing the month and the year is the 
same as first dose date then use first dose date, else January will be 
used for the start month. 
• If a stop date is missing the day information and month/year is same 
as last study date then use last study date, else last day of the given 
month will be used for the stop day; if a stop date is missing the 
month and year is the same as last study date then use last study date, 
else December will be used for the stop month. 
 
5.2.1.2 Treatment-Emergent Adverse Event Study Part 
TEAE will be summarized by study part in Safety Set using the following 
definitions: 
• Part A + B: will include all TEAE from a start date on or after the 
first dose of APL-2 in Part A up to 8 weeks (56 days) after the last 
Pegcetacoplan (APL-2) 
 
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dose of APL-2 in Part B. 
• Part B: will include all TEAE during Part B which is  any AE with 
a start date on or after the date of first 1080 mg APL-2 dose up to 
the end of 8 weeks (56 days) after the last dose of APL-2 in Part B. 
 
5.2.1.3 Adverse Events of Special Interest and Special Search Categories  
Version 23.0 of MedDRA will be used to classify all AEs.  Per Protocol Version 
1 Amendment 4, Protocol Adverse Events of Special Interest (AESI) include the 
following categories and Standardized MedDRA Queries (SMQ): 
• 
Local or systemic infection of any origin (AE SOC = 
“Infections and Infestations”) 
• Clinically significant decrease in kidney function, defined as 
AE SOC = "Renal and Urinary Disorders” or AE SOC = 
“Investigations” with AE PT = “Blood Creatinine Increased 
Creatinine”  
• Injection site reactions (as collected in eCRF) 
• Thrombotic events (Thrombophlebitis SMQ = 20000081 or 
AEHLGTCD = 10014523, Embolic and Thrombotic Events 
SMQ = 20000115) 
 
Additionally, the following TEAE Special Search Categories will 
include the following: 
• Haemolytic Disorders (SMQ = 20000019) 
• Hypersensitivity (SMQ = 20000214) 
• Sepsis (SMQ =20000234) 
• Infections (any AE under AESOC = “Infections and 
Infestations”) 
• Thrombosis 
(Thrombophlebitis 
SMQ 
= 
20000081 
or 
AEHLGTCD = 10014523, Embolic and Thrombotic Events 
SMQ = 20000115) 
 
Pegcetacoplan (APL-2) 
 
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AESIs will be determined by a review of all AEs by the clinical and data 
management study staff. This review will allow for the inclusion of AEs 
of special interest arising during the study that are not on the above list, 
based on a clinical decision. It is expected that documentation of the AEs 
of special interest will be maintained outside the Medrio database 
system by the biostatistics and data management staff (with review by 
medical) and used by the programmer for analysis of the AEs of special 
interest. 
 
5.2.1.4 Time to Onset and Exposure Adjusted Incidence 
For summary tables that summarize time-at-risk exposure adjusted 
incidence, the following definitions will be used.  
 
Part A + B: 
Part A + B Exposure-adjusted incidence (EAI) of an AE event is defined 
as the number of events divided by the total duration of exposure of the 
subjects at risk during the entire Part A + B treatment, which is 
computed as following: 
 
 
Part A + B Exposure Adjusted incidence rate (e) = n*100/EYA+B 
where: 
• n is the number of subjects with an event 
• Exposure year (EYA+B) = (sum of time to onset of the 
event)/365.25 
• Time to onset of the event = date of onset of event – 
date of the first APL-2 dose +1 
 
For subjects without the event, time to onset is censored as follows:  
Time to onset of the event = last dose date + 56 days –  
first APL-2 dose date +1 
 
For subjects who experienced the same event on multiple occasions:  
Pegcetacoplan (APL-2) 
 
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Time to onset of the event = date of onset at the first occasion –  
first APL-2 dose date +1 
 
Part B: 
Part B EAI will be determined for Part B TEAE (i.e. AE with a start date 
on or after the date of first 1080 mg APL-2 dose). It is defined as the 
number of events divided by the total duration of exposure of the 
subjects at risk during Part B treatment, which is computed as following: 
 
 
Part B Exposure Adjusted incidence rate (e) = n*100/EYB 
where: 
• n is the number of subjects with an event 
• Exposure year (EYB) = (sum of time to onset of the 
event)/365.25 
• Time to onset of the event = date of onset of event – 
date of the first 1080 APL-2 dose +1   
 
For subjects without the event, time to onset is censored as follows:  
Time to onset of the event = last dose date + 56 days –  
first 1080 mg APL-2 dose date +1 
 
For subjects who experienced the same event on multiple occasions:  
Time to onset of the event = date of onset at the first occasion –  
first 1080 mg APL-2 dose date +1 
 
5.2.1.5 Adverse Event Listings 
An AE data listing of all AEs collected on study, including verbatim term, 
preferred term, treatment, severity, and relationship to treatment will be 
provided. Serious Adverse Events (SAEs), adverse events of special 
interest, and details of subjects withdrawing due to adverse events will 
also be listed. A Study Day in Part A + B relative to Part A Baseline, a 
Pegcetacoplan (APL-2) 
 
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Study Day in Part B relative to Part B Baseline, and the duration of AEs 
will be included in listings.  
 
5.2.1.6 Adverse Event Summary Tables  
Adverse Event tables will include summaries for TEAE in Part A + B and 
for TEAE in Part B.  
Overall Summary Table  
An overall AE summary will present the number of events and the 
frequency of subjects by cohort and by study part (Cohort 1 wAIHA Part 
A + B / Cohort 1 wAIHA Part B / Cohort 2 CAD Part A + B / Cohort 2 
CAD Part B) with the following categories: 
• any TEAE 
• any TEAE considered as least possibly related to study drug 
(evaluated by the investigator as Possibly Related, Probably 
Related, Definitely Related, or Unknown) 
• any serious TEAE  
• Maximum severity TEAE of mild, moderate, severe, life 
threatening, and death, i.e. a subject with TEAEs at different 
intensities will be summarized at the most severe intensity  
• any TEAE of special interest  
• any TEAE leading to study drug discontinuation  
• any TEAE leading to death 
 
The total number of unique terms within subjects will also be presented 
in each of the categories above, counting each TEAE PT only once 
within each subject. Additionally, the total number of unique terms 
within cohorts will be presented in each of the categories above, 
counting each TEAE PT only once within each cohort. 
 
Summary Tables by SOC and PT 
The following tables will be presented with the number of events and 
the number/percent of subjects by cohort and by study part (Cohort 1 
Pegcetacoplan (APL-2) 
 
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wAIHA Part B / Cohort 1 wAIHA Part A+ B / Cohort 2 CAD Part B / 
Cohort 2 CAD Part A + B).  
• Non-ISR TEAEs by SOC and preferred term, including 
exposure-adjusted incidence 
• TEAEs regarded as at least possibly related to study drug by 
SOC and preferred term, including exposure-adjusted 
incidence 
• Injection Site Reaction TEAEs by SOC and preferred term, 
including exposure-adjusted incidence 
• Serious AEs by SOC and preferred term, including exposure-
adjusted incidence 
 
The summaries above will be ordered by alphabetical SOC and 
descending order of total event count of the term in Part A + B for the 
PT within each SOC.  
 
Summary Tables by SOC, PT, and Maximum Severity 
The following will also be tabulated with the number/percent of subjects 
by cohort and study part (wAIHA Part B / wAIHA Part A + B / CAD 
Part B / CAD Part A + B): 
• TEAEs by SOC, preferred term, and maximum severity 
• Serious TEAE by SOC, preferred term, and maximum 
severity 
• TE Protocol AESIs by SOC, preferred term, and maximum 
severity 
• Related TE Protocol AESIs (regarded as at least possibly 
related to study drug) by SOC, preferred term, and maximum 
severity 
• TEAE of Special Search Categories by SOC, preferred term, 
and maximum severity 
• Related TEAE of Special Search Categories (regarded as at 
least possibly related to study drug) by SOC, preferred term, 
and maximum severity 
Pegcetacoplan (APL-2) 
 
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The summaries above will be ordered alphabetical SOC and alphabetical 
PT within each SOC.  
 
5.2.2 Clinical Laboratory Tests 
5.2.2.1 Clinical Laboratory Normalization 
Some laboratory parameters will be collected by central and local laboratories. 
In the cases where a visit’s sample is collected on both central and local labs, 
the central lab result will be presented in the TLF. In the cases where only local 
labs are available, the local lab data will be normalized using the method 
developed by Stein (Stein, 1992, 2001).  
 
The procedure for the normalization of local lab results will be followed for all 
local lab values with different normal ranges than the central lab: 
1. Convert all parameters’ units from different local lab units to SI units. 
 
2. Impute the local normal ranges as shown below. 
 
3. Assume there is one central Lab (LabConnect) and all NRLO(CL) and 
NRHI(CL) are sourced from Appendix IV of LabConnect’s Central 
Scope of Work 1.0 11 July 2017 and gender/age specific normal ranges 
are used when applicable.  
i.  If the NRLO is missing and NRHI is not missing, then do the 
following: 
NRLO=NRHI * NRLO(CL) / NRHI(CL) 
ii. If the NRHI is missing and NRLO is not missing, then do the 
following:  
NRHI=NRLO * NRHI(CL) / NRLO(CL) 
iii. If both NRLO and NRHI are missing prior to the imputations 
above, do the following:  
NRLO=min (all NRLO including CL) 
and 
NRHI=max (all NRHI including CL),  
Pegcetacoplan (APL-2) 
 
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using sex- or age-specific normal ranges when applicable 
 
4. The following formula will be used to convert local lab value at 
observation level to central lab value: 
 
𝐶𝑒𝑛𝑡𝑟𝑎𝑙 𝑣𝑎𝑙𝑢𝑒 = 𝑁𝑅𝐿𝑂(𝐶𝐿) + 𝑙𝑜𝑐𝑎𝑙 𝑣𝑎𝑙𝑢𝑒−𝑁𝑅𝐿𝑂
𝑁𝑅𝐻𝐼−𝑁𝑅𝐿𝑂
× (𝑁𝑅𝐻𝐼(𝐶𝐿) −𝑁𝑅𝐿𝑂(𝐶𝐿)) 
 
where: 
• NRLO: Low normal range for local lab 
• NRHI: High normal range for local lab 
• NRLO(CL):  Low normal range for central lab 
• NRHI(CL): High normal range for central lab 
 
5. Check for negative Lab values after the normalization. If so, do the 
following: 
a. Set negative value to Zero, or 
b. Use Upper Scale Formula: Central Value = Local value * NRHI 
(CL)/ NRHI, or 
c. Use Lower Scale Formula: Central Value = Local value * NRLO 
(CL)/ NRLO  
(Use a, or b or c as appropriate). 
 
6. Perform the analyses (e.g., CFB) as usual. 
 
5.2.2.2 Potentially Clinically Significant  
Clinical laboratory test values are potentially clinically significant (PCS) if they 
meet either the low or high PCS criteria listed in Table 3 below.   
 
 
 
Pegcetacoplan (APL-2) 
 
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Table 3: Criteria for Potentially Clinically Significant Laboratory Tests 
Parameter 
Criteria 
Hematology 
WBC (total) (x10^9/L) 
<3.0 
> 16 
Lymphocyte (x10^9/L) 
< 0.5 
< 0.8 
> 12 
Neutrophils (x10^9/L) 
< 1.0 
< 1.5 
> 12 
RBC (x10^12/L) 
< 3.3 
> 6.8 
Hemoglobin (g/dL) 
< 10 
Platelet count (x10^9/L) 
< 100 
> 600 
Serum Chemistry 
ALT 
> 1.5xULN 
> 3.0xULN 
AST 
> 1.5xULN 
> 3.0xULN 
Total Serum Bilirubin 
> 1.5xULN 
GGT 
> 1xULN 
ALT or AST > 3xULN and concurrent elevated total 
bilirubin defined as     
> 1.5xULN 
> 2.0xULN 
 
For all other serum chemistry, coagulation, and urinalysis parameters, abnormal 
values per the central lab reference range (for central lab results) or normalized 
reference ranges (for normalized lab results) will be used as potentially clinically 
significant.  
 
5.2.2.3 Clinical Laboratory Listings 
Non-efficacy Chemistry, Non-efficacy Hematology, Coagulation, Urinalysis, 
non-PD Cytometry, and Miscellaneous (which includes the Anti-APL-2 AB 
Pegcetacoplan (APL-2) 
 
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Assay) results will be listed for Safety Set. Additionally, separate PCS listings 
for subjects with at least one PCS result will be presented for each of the above 
laboratory categories. 
 
Listings of all lab results with their corresponding changes from baseline 
(Change from Part A + B Baseline and Change from Part B Baseline for 
assessments after the first 1080 mg APL-2 dose) will be presented. Change from 
Part A + B Baseline will be considered as the pre-dose measure on Study Day 1, 
or the screening assessment if missing the Study Day 1 assessment. Part B 
Baseline will be considered as the last assessment before the first 1080mg APL-
2 dose for each subject. Potentially Clinically Significant laboratory values will 
be identified in listings per Section 5.2.2.2, using high and low flags. 
 
5.2.2.4 Clinical Laboratory Summary Tables 
Non-efficacy Chemistry, Non-efficacy Hematology, Coagulation, Urinalysis, 
non-PD Cytometry, and Miscellaneous results will be summarized separately.  
 
Descriptive Statistics: 
Descriptive statistics will be presented by cohort (Cohort 1 wAIHA / Cohort 2 
CAD) on Safety Set as follows: 
• Part A + B: Part A + B Baseline, all post-baseline scheduled visits 
through the end of study, and change from Part A + B Baseline.  
• Part B: Part B Baseline, all scheduled visits in Part B (i.e. on and after 
the first 1080 mg APL-2 dose), and change from Part B Baseline.  
 
PCS Frequencies: 
The frequency of PCS values at all scheduled visits on-study will be presented 
by cohort (Cohort 1 wAIHA / Cohort 2 CAD) on the safety set. At each visit, 
the number of subjects evaluable will be presented with the frequency and 
percent of subjects with low, normal, and high PCS results. The percentages 
will be calculated relative to the number of subjects with available baseline 
values and at least 1 post-baseline assessment. The numerator is the total 
Pegcetacoplan (APL-2) 
 
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5.2.3.3 Vital Signs Summary Tables 
Descriptive Statistics: 
Descriptive statistics will be presented by cohort (Cohort 1 wAIHA / Cohort 2 
CAD) on Safety Set as follows: 
• Part A + B: Part A + B Baseline, all post-baseline scheduled visits 
through the end of study and change from Part A + B Baseline.  
• Part B: Part B Baseline, all scheduled visits in Part B (i.e. on and after 
the first 1080 mg APL-2 dose), and change from Part B Baseline.  
 
PCS Frequencies: 
The frequency of PCS values at all scheduled visits on-study will be presented 
by cohort (Cohort 1 wAIHA / Cohort 2 CAD) on the safety set. At each visit, 
the number of subjects evaluable will be presented with the frequency and 
percent of subjects with low, normal, and high PCS results. The percentages 
will be calculated relative to the number of subjects with available baseline 
values and at least 1 post-baseline assessment. The numerator is the total 
number of subjects by-visit with at least 1 post-baseline PCS value and 
denominator is the number of subjects with evaluable assessment in the cohort 
at the respective visit. 
 
5.2.4 Electrocardiogram (ECG) 
ECG data is not scheduled to be collected in Part B Long-term Extension Phase; 
therefore, ECG summaries will not be summarized. ECG data that was collected 
after visit 15 of Part A will be presented in listings. 
 
5.2.5 Physical Examination 
Physical examination data will be summarized in listing(s).  
 
 
5.3 
Exploratory Efficacy and Pharmacodynamic Analyses 
While the primary objective of this study is safety, exploratory efficacy and 
pharmacodynamic analyses will be presented. All efficacy listings will include 
Pegcetacoplan (APL-2) 
 
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Version 1.0 
     
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all subjects in the Intent-to-Treat Set. All PD listings will include all subjects in 
the PD Set. All efficacy summaries will be evaluated on the Intent-to-Treat Set.  
All pharmacodynamic summaries will be evaluated on the PD Set.  
 
5.3.1 Packed Red Blood Cell (PRBC) Transfusions 
5.3.1.1 Transfusions Per Month 
PRBC Transfusions per month will be derived for Part A + B Baseline, Part A 
+ B, Part B Baseline, and Part B as follows: 
• Part A + B Baseline Transfusions Per Month =  
 
# 𝑜𝑓 𝑡𝑟𝑎𝑛𝑠𝑓𝑢𝑠𝑖𝑜𝑛𝑠 𝑖𝑛 365 𝑑𝑎𝑦𝑠 𝑝𝑟𝑖𝑜𝑟 𝑡𝑜 𝑓𝑖𝑟𝑠𝑡 𝐴𝑃𝐿−2 𝑑𝑜𝑠𝑒∗28
365
  
• Part A + B Transfusions Per Month =  
 
 
 
 
# 𝑜𝑓 𝑡𝑟𝑎𝑛𝑠𝑓𝑢𝑠𝑖𝑜𝑛𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐴 𝑎𝑛𝑑 𝑃𝑎𝑟𝑡 𝐵∗28
# 𝑜𝑓 𝑑𝑎𝑦𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐴 𝑎𝑛𝑑 𝑃𝑎𝑟𝑡 𝐵
  
• Part B Baseline Transfusions Per Month =  
 
# 𝑜𝑓 𝑡𝑟𝑎𝑛𝑠𝑓𝑢𝑠𝑖𝑜𝑛𝑠 𝑖𝑛 365 𝑑𝑎𝑦𝑠 𝑝𝑟𝑖𝑜𝑟 𝑡𝑜 𝑓𝑖𝑟𝑠𝑡 1080 𝑚𝑔 𝐴𝑃𝐿−2 𝑑𝑜𝑠𝑒∗28
365
 
• Part B Transfusions Per Month = 
# 𝑜𝑓 𝑡𝑟𝑎𝑛𝑠𝑓𝑢𝑠𝑖𝑜𝑛𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐵∗28
# 𝑜𝑓 𝑑𝑎𝑦𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐵
  
 
5.3.1.2 Units Per Month 
PRBC units per month will be derived for Part A + B Baseline, Part A + B, 
Part B Baseline, and Part B as follows: 
• Part A + B Baseline Units Per Month =  
 
# 𝑜𝑓 𝑢𝑛𝑖𝑡𝑠 𝑖𝑛 365 𝑑𝑎𝑦𝑠 𝑝𝑟𝑖𝑜𝑟 𝑡𝑜 𝑓𝑖𝑟𝑠𝑡 𝐴𝑃𝐿−2 𝑑𝑜𝑠𝑒∗28
365
  
• Part A + B Units Per Month =  
 
 
 
 
# 𝑜𝑓 𝑢𝑛𝑖𝑡𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐴 𝑎𝑛𝑑 𝑃𝑎𝑟𝑡 𝐵∗28
# 𝑜𝑓 𝑑𝑎𝑦𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐴 𝑎𝑛𝑑 𝑃𝑎𝑟𝑡 𝐵  
• Part B Baseline Units Per Month =  
Pegcetacoplan (APL-2) 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
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# 𝑜𝑓 𝑢𝑛𝑖𝑡𝑠 𝑖𝑛 365 𝑑𝑎𝑦𝑠 𝑝𝑟𝑖𝑜𝑟 𝑡𝑜 𝑓𝑖𝑟𝑠𝑡 1080 𝑚𝑔 𝐴𝑃𝐿−2 𝑑𝑜𝑠𝑒∗28
365
 
• Part B Units Per Month = 
# 𝑜𝑓 𝑢𝑛𝑖𝑡𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐵∗28
# 𝑜𝑓 𝑑𝑎𝑦𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑃𝑎𝑟𝑡 𝐵  
 
5.3.1.3 Transfusions Listings 
The following listings will be prepared: 
• Transfusion History, for all transfusions recorded in the 365 days prior 
to enrollment 
• On-Study Transfusions, for all transfusions recorded on-study, where 
study part will be specified 
• PRBC Transfusions and Units Per Month which will include: 
o Part A + B PRBC:  
▪ Number of Days during Part A + B Baseline Period 
(365 days) and Number of Days during Part A and B 
▪ Part A + B Baseline Transfusions Per Month and Part A 
+ B Transfusions Per Month  
▪ Part A + B Baseline Units Per Month and Part A + B 
Units Per Month  
o Part B PRBC:  
▪ Number of Days during Part B Baseline Period (365 
days) and Number of Days during Part B 
▪ Part B Baseline Transfusions Per Month and Part B 
Transfusions Per Month  
▪ Part B Baseline Units Per Month and Part B Units Per 
Month  
 
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
Confidential


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
5.3.1.4 Transfusions Summary Tables 
The following tabular summaries will be prepared: 
• Part A + B PRBC: Summary statistics will be prepared by Cohort 
(Cohort 1 wAIHA / Cohort 2 CAD) for the ITT Set and Per Protocol 
Set who have Part A + B Baseline or at least one post-Part A + B 
Baseline PRBC transfusion during Part A + B phase:  
o Part A + B Baseline Transfusions Per Month 
o Part A + B Transfusions Per Month 
o Part A + B Baseline Units Per Month 
o Part A + B Units Per Month 
• Part B PRBC: Summary statistics will be prepared by Cohort (Cohort 
1 wAIHA / Cohort 2 CAD) for the ITT Set and Per Protocol Set who 
have Part B Baseline or at least one post-Part B Baseline PRBC 
transfusion during Part B Phase:  
o Part B Baseline Transfusions Per Month 
o Part B Transfusions Per Month 
o Part B Baseline Units Per Month 
o Part B Units Per Month 
 
5.3.2 Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue 
Scale 
5.3.2.1 FACIT Fatigue Score 
The FACIT Fatigue Scale (Version 4) questionnaire is an exploratory 
efficacy endpoint. The FACIT Fatigue Scale is a 13 item Likert scaled 
instrument which is self-administered by the subjects during clinic 
visits. Subject are presented with 13 statements and asked to indicate 
their responses as it applies to the past 7 days. The 5 possible responses 
are ‘Not at all’ (0), ‘A little bit’ (1), ‘Somewhat’ (2), ‘Quite a bit’ (3) 
Pegcetacoplan (APL-2) 
 
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Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
and ‘Very much’ (4). With 13 statements, the total score has a range of 
0 to 52. Before calculating the total score, most responses (all except 
Item Codes 5 and 7 of the FACIT Fatigue Scale Version 4) are reversed 
to ensure that the higher score corresponds to a higher quality of life.   
 
Study Day 1 will be considered the Part A+ B Baseline for the FACIT 
assessment. If this is missing, change from Part A + B baseline will not 
be calculated. Part B Baseline will be considered as the last assessment 
before the first 1080mg APL-2 dose for each subject. 
 
The FACIT and all related works are owned and copyrighted by, and the 
intellectual property of 
, Ph.D.  Permission for use of the 
FACIT-FATIGUE questionnaire is obtained by contacting 
 at 
information@facit.org. 
 
5.3.2.2 FACIT Listings 
The following listings will be prepared: 
• FACIT Fatigue Scale Questionnaire Responses 
• FACIT Fatigue Score and Change from Baseline which will include: 
o Part A + B:  
▪ FACIT Fatigue Score Results at all Part A + B visits 
with Change from Part A + B Baseline and Percent 
Change from Part A + B Baseline 
o Part B:  
▪ FACIT Fatigue Score Results at all Part B visits with 
Change from Part B Baseline and Percent Change from 
Part B Baseline 
 
 
Pegcetacoplan (APL-2) 
 
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Confidential
PPD
PPD


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
5.3.2.3 FACIT Summary Tables 
The following tabular summaries will be prepared by Cohort (Cohort 1 
wAIHA / Cohort 2 CAD) for ITT Set and Per Protocol Set for the following: 
• Part A + B FACIT Fatigue Score:: 
o FACIT Fatigue Score results at all scheduled visits through Part 
A Visit 15 and from Part B Baseline through the end of study 
o Change from Part A + B Baseline FACIT Fatigue Score at all 
post-baseline visits through Part A Visit 15 and from Part B 
Baseline through end of study 
o Percent Change from Part A + B Baseline FACIT Fatigue 
Score at all post-baseline visits through Part A Visit 15 and 
from Part B Baseline through end of study 
• Part B FACIT Fatigue Score:  
o FACIT Fatigue Score results at Part B Baseline and all 
scheduled Part B visits 
o Change from Part B Baseline FACIT Fatigue Score ay all post-
baseline visits 
o Percent Change from Part B Baseline FACIT Fatigue Score at 
all post-baseline visits 
 
5.3.2.4 FACIT Summary Figures 
The following figures will be prepared: 
• Part A + B FACIT Fatigue Score: Mean score ± SE will be presented 
by Cohort (Cohort 1 wAIHA / Cohort 2 CAD) for the ITT Set and Per 
Protocol Set for the following: 
o FACIT Fatigue Score results at all scheduled visits through Part 
A Visit 15 and from Part B Baseline through end of study 
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
Confidential


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
o Change from Part A + B Baseline FACIT Fatigue Score at all 
post-baseline visits through Part A Visit 15 and from Part B 
Baseline through end of study 
• Part B FACIT Fatigue Score: 
o Change from Part B Baseline FACIT Fatigue Score from Part B 
Baseline through end of study 
 
5.3.3 Linear Analog Self-Assessment (LASA) 
5.3.3.1 LASA Overall Quality of Life and Subscales 
The LASA, which consists of five single statements asking respondents 
to rate, on zero to ten scales, their perceived level of functioning (see 
Protocol Section 17.2). 
 
Specific domains include physical well-being (i.e., fatigue, activity 
level), emotional well-being (i.e., depression, anxiety, stress), spiritual 
well-being (i.e., sense of meaning), and intellectual well-being (i.e., 
ability to think clearly, concentrate). An item for overall quality of life 
(QoL) is also included. The Likert scales run from 0 (as bad as it can be) 
to 10 (as good as it can be), where higher ratings suggest higher QoL. 
 
Study Day 1 will be considered the Part A+ B Baseline for the LASA 
assessment. If this is missing, change from Part A + B baseline will not 
be calculated. Part B Baseline will be considered as the last assessment 
before the first 1080mg APL-2 dose for each subject. 
 
5.3.3.2 LASA Listings 
The following listings will be prepared: 
• LASA Domain Responses (Physical Well Being, Emotional Well 
Being, Spiritual Well Being, Intellectual Well Being, and Overall 
Quality of Life) and Change from Baseline which will include: 
Pegcetacoplan (APL-2) 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
o Part A + B:  
▪ LASA Domain Results at all Part A + B visits with 
Change from Part A + B Baseline and Percent Change 
from Part A + B Baseline 
o Part B:  
▪ LASA Domain Results at all Part B visits with Change 
from Part B Baseline and Percent Change from Part B 
Baseline 
 
5.3.3.3 LASA Domain Summary Tables 
The following tabular summaries will be presented for each of the LASA 
Domains (Overall Quality of Life, Physical Well Bring, Emotional Well 
Being, Spiritual Well Being, and Intellectual Well Being) by Cohort (Cohort 1 
wAIHA / Cohort 2 CAD) for the ITT Set and Per Protocol Set for the 
following: 
• Part A + B LASA Domain Scores: 
o LASA Domain Score results at all scheduled visits through Part 
A Visit 15 and from Part B Baseline through end of study 
o Change from Part A + B Baseline LASA Domain Score at all 
post-baseline visits through Part A Visit 15 and from Part B 
Baseline through end of study 
o Percent Change from Part A + B Baseline LASA Domain 
Score at all post-baseline visits through Part A Visit 15 and 
from Part B Baseline through end of study 
• Part B LASA Domain Scores:  
o LASA Domain Score results at Part B Baseline and all 
scheduled Part B visits 
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
Confidential


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
o Change from Part B Baseline LASA Domain Score at all post-
baseline visits 
o Percent Change from Part B Baseline LASA Domain Score at 
all post-baseline visits 
 
5.3.3.4 LASA Domain Summary Figures 
The Mean score ± SE figures will be presented for each of the LASA Domains 
(Overall Quality of Life, Physical Well Bring, Emotional Well Being, 
Spiritual Well Being, and Intellectual Well Being) by Cohort (Cohort 1 
wAIHA / Cohort 2 CAD) for the ITT Set and Per Protocol Set for the 
following: 
• Part A + B LASA Domain Scores: 
o LASA Domain Score results at all scheduled visits through Part 
A Visit 15 and from Part B Baseline through end of study 
o Change from Part A + B Baseline LASA Domain Score at all 
post-baseline visits through Part A Visit 15 and from Part B 
Baseline through end of study 
• Part B LASA Domain Scores:  
o Change from Part B Baseline LASA Domain Score from Part B 
Baseline through end of study 
 
5.3.4 Efficacy Laboratory Parameters 
5.3.4.1 Parameters and Normalization 
Efficacy laboratory parameters include the following: 
1. Lactate Dehydrogenase 
2. Reticulocytes 
3. Hemoglobin 
4. Haptoglobin 
5. Indirect Bilirubin 
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
Confidential


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
 
Study Day 1 will be considered the Part A+ B Baseline for the efficacy 
lab assessments. If this is missing, the screening assessment, if available, 
will be used as Part A + B Baseline. Part B Baseline will be considered 
as the last assessment before the first 1080 mg APL-2 dose for each 
subject. 
 
Some laboratory parameters will be collected by central and local 
laboratories. In the cases where a visit’s sample is collected on both 
central and local labs, the central lab result will be presented in the TLF. 
In the cases where only local labs are available, the local lab data will 
be normalized using the procedure outlined in Section 5.2.2.1.  
 
5.3.4.2 Efficacy Laboratory Listings 
The following listings will be prepared: 
• Efficacy Laboratory Results and Change From Baseline will be 
presented in separate listings which will include: 
o Part A + B:  
▪ Lab Results at all Part A + B visits with Change from 
Part A + B Baseline and Percent Change from Part A + 
B Baseline 
o Part B:  
▪ Lab Results at all Part B visits with Change from Part B 
Baseline and Percent Change from Part B Baseline 
 
5.3.4.3 Efficacy Laboratory Summary Tables 
The following tabular summaries will be presented for each efficacy 
laboratory parameter by Cohort (Cohort 1 wAIHA / Cohort 2 CAD) for the 
ITT Set and Per Protocol Set for the following: 
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
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Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
• Part A + B Lab Results:  
o Lab results at all scheduled visits through Part A Visit 15 and 
from Part B Baseline through end of study 
o Change from Part A + B Baseline lab result at all post-baseline 
visits through Part A Visit 15 and from Part B Baseline through 
end of study 
o Percent Change from Part A + B Baseline lab result at all post-
baseline visits through Part A Visit 15 and from Part B 
Baseline through end of study 
• Part B Lab Results:  
o Lab results at Part B Baseline and all scheduled Part B visits 
o Change from Part B Baseline lab result at all post-baseline 
visits 
o Percent Change from Part B Baseline lab result at all post-
baseline visits 
 
5.3.4.4 Efficacy Laboratory Summary Figures 
The Mean result ± SE will be presented by cohort (Cohort 1 wAIHA / Cohort 
2 CAD) for each of the laboratory parameters for the ITT Set and Per Protocol 
Set as the following: 
• Part A + B Lab Results: 
o Lab results at all scheduled visits through Part A Visit 15 and 
from Part B Baseline through end of study 
o Change from Part A + B Baseline lab result at all post-baseline 
visits through Part A Visit 15 and from Part B Baseline through 
end of study 
 
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
Confidential


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
• Part B Lab Results:  
o Change from Part B Baseline lab results at all post-baseline 
visits 
5.3.5 Pharmacodynamics 
5.3.5.1 Parameters 
PD parameters include the following: 
1. Complement CH50 
2. Complement AH50 
3. Complement C3 
 
Additional PD parameters also include the following: 
• C3 deposition on RBCs  
- 
Percent Type I 
- 
Percent Type II 
- 
Percent Type III  
- 
Percent Type I+II 
- 
Percent C3d on RBC 
where: 
%𝐶3𝑑 𝑜𝑛 (𝑇𝑦𝑝𝑒 𝐼+ 𝐼𝐼 𝑅𝐵𝐶𝑠)
=
(𝐸𝑣𝑒𝑛𝑡𝑠 (𝐶3𝑑 (𝐶𝐷59 𝐻𝑖𝑔ℎ𝑇𝑦𝑝𝑒1 𝑛𝑜𝑟𝑚 𝑅𝐵𝐶) + 
𝐸𝑣𝑒𝑛𝑡𝑠 (𝐶3𝑑(𝐶𝐷59 𝑑𝑖𝑚 𝑇𝑦𝑝𝑒 𝐼𝐼 𝑅𝐵𝐶)
)
(𝐸𝑣𝑒𝑛𝑡𝑠 𝐶𝐷59 ℎ𝑖𝑔ℎ 𝑇𝑦𝑝𝑒 1 𝑛𝑜𝑟𝑚 (𝑅𝐵𝐶) + 
𝐸𝑣𝑒𝑛𝑡𝑠 𝐶𝐷59 𝑑𝑖𝑚 𝑇𝑦𝑝𝑒 𝐼𝐼 (𝑅𝐵𝐶)
)
 𝑥 100 
 
and where: 
% 𝐶3𝑑 𝑜𝑛 𝑅𝐵𝐶 = 𝐶3𝑑+ 𝐺𝑙𝑦 𝑅𝐵𝐶 𝐸𝑣𝑒𝑛𝑡𝑠
𝐺𝑙𝑦+ 𝑅𝐵𝐶 𝐸𝑣𝑒𝑛𝑡𝑠
 𝑥 100 
 
Study Day 1 will be considered the Part A+ B Baseline for the PD 
assessments. If this is missing, the screening assessment, if available, 
will be used as Part A + B Baseline. Part B Baseline will be considered 
as the last assessment before the first 1080mg APL-2 dose for each 
subject. 
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
Confidential


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
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5.3.5.2 PD Listings 
The following listings will be prepared for the PD Set: 
• PD Results and Change from Baseline will be presented in separate 
listings which will include: 
o Part A + B:  
▪ PD Results at all Part A + B visits with Change from 
Part A + B Baseline and Percent Change from Part A + 
B Baseline 
o Part B:  
▪ PD Results at all Part B visits with Change from Part B 
Baseline and Percent Change from Part B Baseline 
 
5.3.5.3 PD Summary Tables 
• The following summary statistics will be presented for each of the PD 
parameters by Cohort (Cohort 1 wAIHA / Cohort 2 CAD) for the PD 
Set and Per Protocol Set for the following: 
• Part A + B PD Results:  
o Lab results at all scheduled visits through Part A Visit 15 and 
from Part B Baseline through end of study 
o Change from Part A + B Baseline lab result at all post-baseline 
visits through Part A Visit 15 and from Part B Baseline through 
end of study 
o Percent Change from Part A + B Baseline lab result at all post-
baseline visits through Part A Visit 15 and from Part B 
Baseline through end of study 
• Part B PD Results:  
o Lab results at Part B Baseline and all scheduled Part B visits 
Pegcetacoplan (APL-2) 
 
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Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
o Change from Part B Baseline lab result at all post-baseline 
visits 
o Percent Change from Part B Baseline lab result at all post-
baseline visits 
 
5.3.5.4 PD Summary Figures 
The following figures mean result ± SE will be presented by cohort (Cohort 1 
wAIHA / Cohort 2 CAD) for each of the PD parameters (CH50, AH50, 
Complement C3, C3d Type I, C3d Type II, C3d Type I+II, and C3d on RBC) 
for the PD Set and Per Protocol Set: 
• Part A + B PD Results:  
o Lab results at all scheduled visits through Part A Visit 15 and 
from Part B Baseline through end of study 
o Change from Part A + B Baseline lab result at all post-baseline 
visits through Part A Visit 15 and from Part B Baseline through 
end of study 
• Part B PD Results:  
o Change from Part B Baseline lab results at all post-baseline 
visits 
5.3.6 Anti-drug antibody Assay  
 This data will be presented in listings.  
 
5.4 
Pharmacokinetic Analysis 
All summaries and analyses of the pharmacokinetic data will be based on the 
Pharmacokinetic Set. 
5.4.1 
Pharmacokinetic Concentration Summaries 
APL-2 concentrations reported as below the limit of quantification (BLQ) will 
be taken as zero for linear plots, and equal to the lower limit of quantification 
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
Confidential


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
(LLOQ) for semi-logarithmic plots.  For the computation of descriptive 
statistics, BLQ will be taken as zero, except for the calculation of the 
geometric mean where the LLOQ will be used. 
 
A listing of all APL-2 concentrations will be presented by dose.  The actual study 
time will be listed, along with the deviation and percent deviation from nominal 
time. 
 
For Part A, APL-2 concentrations will be summarized by planned study visit 
windows using descriptive statistics by randomized dose group, actual dose at 
the time of the visit. That is, at each visit, the descriptive statistics will be 
presented for: 
• All randomized 270mg dose group, regardless of current dose 
• All randomized 360mg dose group, regardless of current dose 
• Subjects randomized to 270mg and on 270mg dose at time of visit 
• Subjects randomized to 360mg and on 360mg dose at time of visit 
 
For Part B, APL-2 concentrations will be summarized by planned study visit 
windows using descriptive statistics by cohort. The number of subjects with a 
value > BLQ will also be tabulated.   
 
If a subject discontinues APL-2 dosing, then concentrations from samples 
collected more than 1 day after the last dose will be excluded from calculations.   
 
For Part A, Linear and log-linear (± SE) concentration profile plots against time 
will be produced for each dose group.  
 
For Part B, Linear and log-linear (± SE) concentration profile plots against time 
will be produced for each cohort. 
 
For all time on-study, individual plots will be presented for PK concentration by 
study day. The individual plots will include an overlay of APL-2 dosing, also 
aligned by study day.  
Pegcetacoplan (APL-2) 
 
Apellis Pharmaceuticals, Inc
Confidential


Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
 
5.4.2 
Pharmacokinetic Parameters 
For both Part A and Part B, the following PK parameter for APL-2 will be 
derived using actual sample times: 
Ctrough,max 
Maximal observed serum concentration. As later PK samples 
  
 
are collected pre-dose this is termed maximal trough  
  
 
concentration.  
 
Ctrough,max will be calculated for both 270 mg and 360 mg where subjects receive 
both doses during Part A, and for Part B 
 
The derived PK parameter will be listed by cohort and dose (for Ctrough,max). The 
PK parameter will also be summarized using descriptive statistics. Geometric 
mean and CV will be included in the descriptive statistics.  
 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
6. TESTING/QUALITY CONTROL PLAN AND SOFTWARE/SYSTEM 
All statistical programs, excluding PK analysis programs, will be written in SAS® version 
9.4.  Statistical programs will be tested and reviewed for Quality Control (QC) by a second 
programmer/biostatistician not involved in the programming as per DPC’s standard 
operating procedure (SOP). In addition, DPC’s SOP will be followed to ensure that the 
information is complete, consistent, and accurately reflects the data stored in the database.  
Further all TLFs will undergo a QC process by an independent biostatistician/programmer 
to ensure that the information is complete, consistent, and accurately reflects the data.  
 
6.1 
Programming Specifications for TLFs 
Appendix 8.1 provides a list of all the TLFs that are planned to be produced. 
 
6.2 
Formatting Conventions 
The following formatting conventions will be used to output TLFs:  
• 
TLFs are outputted by SAS Output Delivery System (ODS) into Rich 
Text Files (RTF) format. 
• 
Tables and Listings will include borders around all headings and data 
cells. 
• 
Output will be in landscape orientation with margins of 0.75 inches on 
bottom, left, and top, and 3/8 inch for right. 
• 
The default font to be in tables/listings/figures will be Courier New.  
• 
Preferred and minimum font size: 
 
Portion of Output 
Preferred 
Minimum 
Page Header 
9 pt 
8 pt 
Title 
9 pt  
8 pt 
Column header 
9 pt  
8 pt 
Cells 
9 pt 
8 pt 
Footnote 
9 pt  
8 pt 
Page Footer 
9 pt 
8 pt 
 
• 
Data will be centered within columns when the maximum length of the 
data being displayed is less than or equal to the maximum width of the 
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Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
column heading. When the maximum length of the data being displayed 
exceeds the maximum width of the column heading, the data will be 
left-justified. 
• 
Column headings should be in initial capital characters.  For numeric 
variables, include “unit” in the column heading when appropriate. 
• 
In figures, axes will be labeled appropriately. 
  
6.3 
Standard Text Conventions 
6.3.1 Header 
All output (table, listing, or figure) will have the following header, as 
applicable: 
 
Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208 
       
 
 
 
Page xx of XX 
Part B Long-Term Extension Study Report 
 
All output will have the date and time (date and time output was 
generated) 
and 
internal 
page 
number 
in 
the 
header.  
Tables/Listings/Figures should be internally paginated (i.e., page 
numbers should appear sequentially within each output). 
 
6.3.2 Title 
At least three (3) lines, in general, will be reserved for the entire title.  
• 
The first line is for the table/listing/figure number;  
• 
The second line is for the actual title; and  
• 
The third line is reserved for the analysis set descriptor.  
 
All titles will be centered, as shown in the following example: 
 
 
Table 14.3.1.1 
Topline Summary of Adverse Events  
Safety Set 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
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6.3.3 Footnotes 
Unless otherwise specified, footnotes will appear on all pages within the 
tables and listings as follows: 
• Footnotes will be in the format of “NOTE: then the footnotes”, as 
shown in the following example:  
 
• 
NOTE: SD = Standard Deviation.  
 
• Each line of a complete footnote should end with a period. 
• When an abbreviation (e.g. AE, SAE, etc.) appears first time in the 
whole set of TLFs for a study, a footnote should be provided at least 
once; and it is up to the study statistician, to decide whether there is a 
need to repeat the same footnote for the rest of TLFs.  
• A footnote serves as a brief explanation/clarification /definition 
/concept of a flag symbol or a character, an abbreviation, a 
terminology, etc., that appears in or relates directly to the displayed 
content of a table/listing/figure.  
• All footnotes will be at the lowest line of the page immediately above 
the footer.  The footer will be directly on the line below the last 
footnote. 
• For Tables, first footnote will provide source listings and/or analysis 
datasets names for cross-referencing. 
 
6.3.4 Footer 
The following footer should appear at the very bottom of each page of a 
table, a listing, or a figure generated in SAS in the lower left corner: 
 
Program Name: PGNAME.sas; Creation Date and Time: DDMMMYYYY HH:MM 
Data Lock DDMMMYYYY HH:MM - ADaM Generated DDMMMYYYY Proprietary and Confidential  
 
where PGNAME = SAS program name. 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
6.4 
Statistical Conventions 
6.4.1 Statistics Reported  
• Unless otherwise specified, the mean and SD will be displayed to 
one more decimal place than the original value, while minimum and 
maximum will be reported in the format of the original data, e.g.:   
Original: xx 
Mean and SD: xx.x 
Minimum and maximum: xx 
• Use of N versus n: 
N = total number of subjects or subjects in the analysis set. 
n = total number of subjects or subjects in the specific category. 
• Descriptive statistics in this template include: N, Mean, Median, SD, 
Minimum, and Maximum.  
• Unless specified in the actual TLF shells for a study, all percentages 
will be rounded to 1 decimal place in all tables/listings/figures.  
Rounding will take place after all calculations have been performed. 
 
6.4.2 Tables Summarizing Categorical Data 
The following specifications apply to tables that summarize categorical 
data: 
• If the categories of a parameter are ordered, then all categories 
between the maximum possible category and the minimum 
category will be included, even if n=0 for a given category 
between the minimum and maximum level for that parameter. 
• If the categories are not ordered, then only those categories for 
which there is at least one subject represented will be included. 
• A missing category will be added to any parameter for which 
information is not available for any subjects. 
• If there were no subjects who met the condition, then a message 
will appear indicating that no subjects met the condition for 
inclusion in that table. 
 
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Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
6.4.3 Subject Data Listings 
In general, individual subject data listings will include the data of all 
non-screen failure subjects.  However, if a subject data listing includes 
only subjects who met a certain condition, and there were no subjects 
who met that condition, then a “message” will appear indicating that no 
subjects met the condition for inclusion in that listing. Data listings will 
provide the derived study day of an assessment or event, where 
appropriate. 
 
 
 
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Apellis Pharmaceuticals, Inc. 
Protocol: APL2-CP-AIHA-208  
Part B Long Term Extension Statistical Analysis Plan 
Version 1.0 
     
    08 Nov 2022 
 
 
     
 
 
 
 
7. REFERENCES 
 
ICH E3 (1995): Structure and Content of Clinical Study Reports. International Conference 
on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for 
Human Use (ICH). 
 
ICH E6 R2 (2016): Integrated Addendum to ICH E6(R1). International Conference on 
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human 
Use (ICH). 
 
ICH E9 (1998): Statistical Principles for Clinical Trials. International Conference on 
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human 
Use (ICH). 
 
MedDRA Version 23.0 (March 2020). International Federation of Pharmaceutical 
Manufacturers and Associations (IFPMA). 
 
Novel Insights into the treatment of complement-medicated hemolytic anemia. Berentsen 
S et al, (2019). Therapeutic Advances in Hematology. Vol 10: 1-20.  
 
SAS® for Windows® Version 9.4. SAS Inc. Cary, North Carolina USA. 
 
The WHO Drug Dictionary (WHO-DD) (March 1, 2021). World Health Organization 
(WHO) Uppsala Monitoring Center (UMC). 
 
 
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