Clinical trial NCT04669600
Conditions: Immune Thrombocytopenia (ITP)
Sponsor: Bioverativ, a Sanofi company
Start date: 2021-02-04; Completion date: 2023-02-07
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Primary Objective:

\- To evaluate the effect of BIVV020 on the durability of platelet response in participants with persistent/chronic immune thrombocytopenia (ITP)

Secondary Objectives:

* To assess the safety and tolerability of BIVV020
* To assess the pharmacokinetics of BIVV020
* To assess the response rate of treatment with BIVV020
* To assess the time to response
* To assess the effect of treatment with BIVV020 on the requirement for rescue ITP therapy
* To assess the immunogenicity of BIVV020

Detailed description:
Study duration:

* Screening period: up to 56 days
* Transition period between last sutimlimab dose and first dose of BIVV020 (for participants who were previously receiving sutimlimab): 14 days, included as part of the 56-day Screening period. Treatment duration: Minimum 52 weeks.

Visit frequency:

* Day 1
* Day 4
* Weeks 1 to 6: Weekly
* Weeks 7 to 12: Every other week
* Weeks 13 to 24: Every 4 weeks
* Weeks 25+: At least every 8 weeks
* End of Study visit: 22 weeks after the last dose of BIVV020

Arms: arm 1: Participants received SAR445088 (BIVV020).
Interventions: intervention 1: SAR445088 (BIVV020)
Intervention descriptions: intervention 1: Pharmaceutical form:solution for injection

Protocol documents:
Prot_000.pdf: 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES  
DOCUMENT HISTORY  
Document 
Country/countries 
impacted by 
amendment 
Date, version 
Amended Clinical Trial Protocol 03 
all 
25 January 2021, Version 1 (electronic 4.0) 
Amended Clinical Trial Protocol 02 
all 
10 December 2020, Version 1 (electronic 2.0) 
Amended Clinical Trial Protocol 01 
all 
08 December 2020, Version 1 (electronic 1.0) 
Original Protocol 
all 
03 September 2020, Version 1 (electronic 2.0) 
Amended protocol 03 (25 Jan 2021) 
This amended protocol 03 (Amendment 03) is not considered to be substantial based on the 
criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the 
Council of the European Union. 
OVERALL RATIONALE FOR THE AMENDMENT  
Changes in the protocol have been implemented to address MHRA requests. 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Section # and Name 
Description of Change 
Brief Rationale 
2.3 Benefit/Risk 
Assessment 
Added information on the benefits and risks of transitioning 
from sutimlimab to BIVV020 
MHRA request 
4.2 Scientific rationale for 
study design  
Added information on the rationale for transitioning patients 
who previously responded to sutimlimab to BIVV020  
MHRA request  
5.1 Inclusion criteria I05 
Restrictions on participant sperm and ova donation added 
MHRA request 
5.2 Exclusion criteria E08 
Participants switching from sutimlimab may be enrolled 
even with a positive SARS-CoV-2 test, based on the 
judgement of the Investigator 
These participants may be at risk 
for severe thrombocytopenia if 
they are unable to receive either 
sutimlimab or BIVV020 
7.1.1 Permanent 
discontinuation 
Added language stating that the replacement of a 
participant who discontinued from the study will not occur in 
the case where the participant was discontinued due to a 
BIVV020-related adverse reaction or safety concern 
MHRA request 
8.2.2 Vital signs; 
8.2.3 Electrocardiograms 
Previous requirements for vital signs assessments and 
electrocardiograms to be conducted prior to clinical 
laboratory assessments have been changed to 
recommendations  
This order of procedures is not 
feasible at some sites 
 
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TABLE OF CONTENTS 
AMENDED CLINICAL TRIAL PROTOCOL 03 .............................................................................................. 1 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................................................................... 2 
TABLE OF CONTENTS .................................................................................................................................. 3 
LIST OF TABLES ........................................................................................................................................... 7 
LIST OF FIGURES .......................................................................................................................................... 7 
1 
PROTOCOL SUMMARY ................................................................................................................. 8 
1.1 
SYNOPSIS ....................................................................................................................................... 8 
1.2 
SCHEMA ........................................................................................................................................ 13 
1.3 
SCHEDULE OF ACTIVITIES (SOA) .............................................................................................. 14 
2 
INTRODUCTION ............................................................................................................................ 19 
2.1 
STUDY RATIONALE...................................................................................................................... 19 
2.2 
BACKGROUND ............................................................................................................................. 19 
2.3 
BENEFIT/RISK ASSESSMENT ..................................................................................................... 20 
2.3.1 
Risk assessment ............................................................................................................................ 24 
2.3.2 
Benefit assessment ........................................................................................................................ 26 
2.3.3 
Overall benefit: risk conclusion ...................................................................................................... 26 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................. 27 
3.1 
APPROPRIATENESS OF MEASUREMENTS .............................................................................. 28 
4 
STUDY DESIGN ............................................................................................................................ 29 
4.1 
OVERALL DESIGN ........................................................................................................................ 29 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN ......................................................................... 30 
4.2.1 
Participant input into design ........................................................................................................... 31 
4.3 
JUSTIFICATION FOR DOSE ........................................................................................................ 31 
4.4 
END OF STUDY DEFINITION ....................................................................................................... 31 
5 
STUDY POPULATION .................................................................................................................. 32 
5.1 
INCLUSION CRITERIA .................................................................................................................. 32 
5.2 
EXCLUSION CRITERIA  ............................................................................................................... 33 
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5.3 
LIFESTYLE CONSIDERATIONS ................................................................................................... 35 
5.4 
SCREEN FAILURES...................................................................................................................... 35 
5.5 
CRITERIA FOR TEMPORARILY DELAYING ENROLLMENT/STUDY INTERVENTION 
ADMINISTRATION ........................................................................................................................ 35 
6 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ................................................... 36 
6.1 
STUDY INTERVENTION(S) ADMINISTERED .............................................................................. 36 
6.1.1 
Intravenous loading dose administration ....................................................................................... 36 
6.1.2 
Subcutaneous dose administration ................................................................................................ 37 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY....................................................... 38 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING ....................................... 38 
6.4 
STUDY INTERVENTION COMPLIANCE ...................................................................................... 38 
6.5 
DOSE MODIFICATION .................................................................................................................. 39 
6.6 
CONTINUED ACCESS TO INTERVENTION AFTER THE END OF THE STUDY....................... 39 
6.7 
TREATMENT OF OVERDOSE ...................................................................................................... 39 
6.8 
CONCOMITANT THERAPY .......................................................................................................... 40 
6.8.1 
Rescue medicine ............................................................................................................................ 40 
7 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................................... 41 
7.1 
DISCONTINUATION OF STUDY INTERVENTION  ..................................................................... 41 
7.1.1 
Permanent discontinuation ............................................................................................................ 41 
7.1.2 
Liver chemistry stopping criteria .................................................................................................... 42 
7.1.3 
QTc stopping criteria ...................................................................................................................... 42 
7.1.4 
Lack of efficacy (relapse or sustained lack of improvement) stopping criteria .............................. 42 
7.1.5 
Thrombocytosis .............................................................................................................................. 42 
7.1.6 
Temporary discontinuation ............................................................................................................. 42 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY .................................. 43 
7.3 
LOST TO FOLLOW UP ................................................................................................................. 43 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................................... 45 
8.1 
EFFICACY ASSESSMENTS  ........................................................................................................ 45 
8.2 
SAFETY ASSESSMENTS  ............................................................................................................ 45 
8.2.1 
Physical examinations ................................................................................................................... 45 
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8.2.2 
Vital signs ....................................................................................................................................... 46 
8.2.3 
Electrocardiograms ........................................................................................................................ 46 
8.2.4 
Clinical safety laboratory assessments .......................................................................................... 46 
8.2.4.1 
Additional testing in case of hypersensitivity/allergic reaction ....................................................... 47 
8.2.4.2 
Additional testing in case of suspected rhabdomyolysis................................................................ 47 
8.2.5 
Pregnancy testing .......................................................................................................................... 47 
8.2.6 
Vaccinations against encapsulated bacteria .................................................................................. 47 
8.2.7 
Injection site reactions ................................................................................................................... 48 
8.2.8 
Phone calls ..................................................................................................................................... 48 
8.2.9 
Participant diary ............................................................................................................................. 48 
8.3 
ADVERSE EVENTS (AES), SERIOUS ADVERSE EVENTS (SAES) AND OTHER 
SAFETY REPORTING ................................................................................................................... 48 
8.3.1 
Time period and frequency for collecting AE and SAE information ............................................... 49 
8.3.2 
Method of detecting AEs and SAEs ............................................................................................... 49 
8.3.3 
Follow-up of AEs and SAEs ........................................................................................................... 49 
8.3.4 
Regulatory reporting requirements for SAEs ................................................................................. 50 
8.3.5 
Pregnancy ...................................................................................................................................... 50 
8.3.6 
Adverse event of special interest ................................................................................................... 51 
8.3.7 
Guidelines for reporting product complaints .................................................................................. 52 
8.4 
PHARMACOKINETICS .................................................................................................................. 52 
8.4.1 
Sampling times ............................................................................................................................... 52 
8.4.2 
Sample handling procedure ........................................................................................................... 52 
8.4.3 
Bioanalytical methods .................................................................................................................... 52 
8.4.4 
Pharmacokinetic parameters ......................................................................................................... 52 
8.5 
GENETICS AND/OR PHARMACOGENOMICS ............................................................................ 52 
8.6 
BIOMARKERS ............................................................................................................................... 52 
8.7 
IMMUNOGENICITY ASSESSMENTS ........................................................................................... 53 
8.8 
HEALTH ECONOMICS OR MEDICAL RESOURCE UTILIZATION AND HEALTH 
ECONOMICS ................................................................................................................................. 53 
8.9 
USE OF BIOLOGICAL SAMPLES AND DATA FOR FUTURE RESEARCH ................................ 53 
9 
STATISTICAL CONSIDERATIONS .............................................................................................. 55 
9.1 
SAMPLE SIZE DETERMINATION ................................................................................................. 55 
9.2 
POPULATIONS FOR ANALYSES ................................................................................................. 55 
9.3 
STATISTICAL ANALYSES ............................................................................................................ 55 
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9.3.1 
General considerations .................................................................................................................. 55 
9.3.2 
Primary endpoint ............................................................................................................................ 56 
9.3.3 
Secondary endpoints ..................................................................................................................... 56 
9.3.4 
Exploratory endpoints .................................................................................................................... 57 
9.3.5 
Safety analysis ............................................................................................................................... 57 
9.3.5.1 
Adverse events .............................................................................................................................. 57 
9.3.5.2 
Laboratory variables and vital signs............................................................................................... 57 
9.3.6 
Other analysis ................................................................................................................................ 57 
9.4 
INTERIM ANALYSES  ................................................................................................................... 58 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ........................ 59 
10.1 
APPENDIX 1: REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ....... 59 
10.1.1 
Regulatory and ethical considerations ........................................................................................... 59 
10.1.2 
Financial disclosure........................................................................................................................ 60 
10.1.3 
Informed consent process .............................................................................................................. 60 
10.1.4 
Data protection ............................................................................................................................... 61 
10.1.5 
Review Committees ....................................................................................................................... 63 
10.1.6 
Dissemination of clinical study data ............................................................................................... 64 
10.1.7 
Data quality assurance .................................................................................................................. 64 
10.1.8 
Source documents ......................................................................................................................... 65 
10.1.9 
Study and site start and closure ..................................................................................................... 65 
10.1.10 Publication policy ........................................................................................................................... 66 
10.2 
APPENDIX 2: CLINICAL LABORATORY TESTS ......................................................................... 67 
10.3 
APPENDIX 3: AES AND SAES: DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING ......................................................................... 68 
10.3.1 
Definition of AE .............................................................................................................................. 68 
10.3.2 
Definition of SAE ............................................................................................................................ 70 
10.3.3 
Recording and follow-up of AE and/or SAE ................................................................................... 71 
10.3.4 
Reporting of SAEs.......................................................................................................................... 73 
10.4 
APPENDIX 4: CONTRACEPTIVE AND BARRIER GUIDANCE ................................................... 74 
10.4.1 
Definitions ...................................................................................................................................... 74 
10.4.2 
Contraception guidance ................................................................................................................. 75 
10.5 
APPENDIX 5: GENETICS ............................................................................................................. 76 
10.6 
APPENDIX 6: SAFETY: SUGGESTED ACTIONS AND FOLLOW-UP ASSESSMENTS ............. 77 
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10.7 
APPENDIX 7: AES, ADES, SAES, SADES, USADES AND DEVICE DEFICIENCIES: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, FOLLOW-UP, 
AND REPORTING IN MEDICAL DEVICE STUDIES .................................................................... 80 
10.8 
APPENDIX 8: COUNTRY-SPECIFIC REQUIREMENTS .............................................................. 80 
10.9 
APPENDIX 9: CONTINGENCY MEASURES FOR A REGIONAL OR NATIONAL 
EMERGENCY THAT IS DECLARED BY A GOVERNMENTAL AGENCY ................................... 80 
10.10 
APPENDIX 10: ABBREVIATIONS ................................................................................................. 81 
10.11 
APPENDIX 11: PROTOCOL AMENDMENT HISTORY ................................................................ 83 
11 
REFERENCES ............................................................................................................................... 86 
 
LIST OF TABLES  
Table 1 - Risk assessment ............................................................................................................................ 24 
Table 2 - Objectives and endpoints ............................................................................................................... 27 
Table 3 - Overview of study interventions administered ............................................................................... 36 
Table 4 - Arms and associated interventions ................................................................................................ 36 
Table 5 - Populations for analyses ................................................................................................................ 55 
Table 6 - Protocol-required laboratory tests .................................................................................................. 67 
Table 7 - Highly effective contraceptive methods ......................................................................................... 75 
 
LIST OF FIGURES  
Figure 1 - Graphical study design ................................................................................................................. 13 
 
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1 
PROTOCOL SUMMARY  
1.1 
SYNOPSIS  
Protocol title:  
A multicenter, Phase 2a, open-label, non-randomized study evaluating the efficacy, 
safety, and tolerability of BIVV020 in adults with persistent/chronic immune 
thrombocytopenia (ITP) 
Brief title: 
A Phase 2a study evaluating BIVV020 in adults with persistent/chronic immune 
thrombocytopenia (ITP) 
Rationale: 
Individuals with immune thrombocytopenia (ITP) who are refractory to current therapies may 
respond to inhibition of the proximal portion of the classical complement pathway (CP). This 
hypothesis is supported by data obtained using a first-generation CP inhibitor, sutimlimab 
(BIVV009), which targets the active and inactive conformations of human serine protease 
complement component 1, s subcomponent (C1s). The current study will assess the efficacy, 
safety, and tolerability of a second-generation CP inhibitor, BIVV020. BIVV020 selectively 
targets the activate conformation of C1s and has a prolonged half-life compared to sutimlimab, 
allowing for subcutaneous (SC) maintenance administration. This study will enroll participants 
who have received sutimlimab in study TDR16218 as well as participants who have not 
previously received sutimlimab (naïve participants).  
Objectives and endpoints  
 
 
Objectives 
Endpoints 
Primary 
• 
To evaluate the effect of BIVV020 on the 
durability of platelet response in participants 
with persistent/chronic immune 
thrombocytopenia (ITP) 
• 
Naïve participants: Proportion of participants with a 
platelet count ≥50 × 109/L at ≥50% of scheduled visits, 
or for participants with baseline platelet count 
<15 × 109/L, a ≥20 × 109/L increase in platelet count 
from baseline at ≥50% of scheduled visits, without 
receiving rescue ITP therapy, as assessed from Week 3 
to Week 24. 
• 
Participants who previously received sutimlimab: 
Proportion of participants with maintenance of platelet 
count ≥30 × 109/L at ≥50% of scheduled visits, without 
receiving rescue ITP therapy, as assessed from Week 3 
to Week 24. 
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Objectives 
Endpoints 
Secondary 
• 
To assess the safety and tolerability of 
BIVV020  
• 
Standard clinical and laboratory parameters and 
adverse events 
• 
To assess the pharmacokinetics (PK) of 
BIVV020  
• 
Plasma concentrations of BIVV020 
• 
To assess the response rate of treatment with 
BIVV020  
• 
Response rate at Weeks 24 and 52, defined as a 
platelet count ≥50 × 109/L and a greater than 2-fold 
increase from baseline, measured on 2 occasions at 
least 7 days apart, with the absence of bleeding 
(bleeding is defined as bleeding with a score ≥2 on the 
WHO bleeding scale), and the lack of combination ITP 
therapy during this period. 
• 
To assess the time to response 
• 
Time from baseline to first platelet response, defined as 
greater than or equal to each of the following values: 
50 × 109/L and 100 × 109/L (confirmed by 
2 measurements at least 7 days apart) 
• 
To assess the effect of treatment with BIVV020 
on the requirement for rescue ITP therapy 
• 
Proportion of participants who did not require rescue 
therapy for an acute episode of thrombocytopenia after 
Week 3 
• 
To assess the immunogenicity of BIVV020 
• 
Incidence and titer (if relevant) of anti-BIVV020 
antibodies 
 
 
Exploratory 
 
 
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Overall design: 
This is a Phase 2a, open-label, non-randomized, international, multicenter study to evaluate the 
efficacy, safety, and tolerability of BIVV020 in adults with persistent/chronic primary ITP. The 
study will enroll approximately 12 participants: up to 6 participants who have received and 
responded to sutimlimab (BIVV009) in study TDR16218, as well as participants who have not 
previously received sutimlimab. 
The Screening Period will be up to 56 days. Screening begins from the time of the signing of the 
informed consent form (ICF). For participants receiving sutimlimab in study TDR16218, they 
may continue to receive sutimlimab during screening, until at least 14 days prior to the first dose 
of BIVV020, as duration of the PD effect of sutimlimab is approximately 14 days. This period 
between the final dose of sutimlimab and the first dose of BIVV020 is known as the Transition 
Period. Enrollment in the study occurs when a participant receives the first dose of BIVV020. 
A loading dose of BIVV020 at 50 mg/kg intravenous (IV) will be administered on Day 1, 
followed by maintenance doses of 600 mg SC weekly starting on Day 8. On Day 1, participants 
will remain in the clinic for at least 4 hours after the start of investigational medicinal product 
(IMP) administration. The 600 mg SC dose will be administered as two 2 mL injections. For the 
first 5 weeks of maintenance therapy, the injections will be performed by the site staff, and 
participants will receive education on self-administration. At Week 6, the participant (or their 
caregiver) will perform the injection under the supervision of the site staff. Participants should be 
observed for 30 minutes after the first 6 SC administrations of IMP. 
From Weeks 7 to 12, participants will return to the clinic every other week. During the weeks they 
are not seen in the clinic, they will administer BIVV020 at home. At clinic visits, participants 
(or their caregiver) will administer BIVV020 under the supervision of the study staff. Participants 
may request assistance with the injections from the study staff during these visits. From Weeks 13 
to 24, participants will return every 4 weeks and will self-administer BIVV020 under the 
supervision of study staff at those visits. From Week 25 onward, visits will occur at a minimum of 
every 8 weeks, and participants will continue to self-administer BIVV020 under the supervision 
of the study staff during those visits. Clinic visits should be scheduled so that they align as closely 
as possible with the day the participant typically takes BIVV020. If a participant prefers for drug 
administration to occur at the site instead of his/her home at any time during the study, this is 
acceptable. 
Phone calls will be performed during the study for site staff to remind participants to take their 
injections, answer any questions they may have regarding the injections, and to assess adverse 
events (AEs). From Weeks 7 to 24, phone calls will be performed on weeks that the participants 
are not seen in the clinic (Weeks 7, 9, 11, 13 to 15, 17 to 19, and 21 to 23). After Week 25, phone 
calls will be performed approximately 4 weeks after each previous visit. (If a visit during this 
period occurs within approximately 4 weeks of the prior visit, a phone call is not necessary) 
Phone calls should continue to occur approximately every 8 weeks after the cessation of 
treatment, until the End of Study (EOS) visit. 
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Maintenance injections will continue until the last participant enrolled has completed 52 weeks of 
treatment. Therefore, the length of maintenance therapy may vary for each participant. The 
maximum duration of treatment for an individual participant is 104 weeks. 
Brief summary: Phase 2 
This is a single group treatment, Phase 2a, open-label, single arm study of BIVV020 in male and 
female participants with persistent/chronic ITP. 
Study duration:  
• Screening Period: up to 56 days 
• Transition Period between last sutimlimab dose and first dose of BIVV020 (for 
participants who were previously receiving sutimlimab): at least 14 days, included as part 
of the 56-day Screening Period 
Treatment duration: 52 weeks (minimum) 
Visit frequency:  
• Day 1 
• Day 4 
• Weeks 1 to 6: Weekly 
• Weeks 7 to 12: Every other week 
• Weeks 13 to 24: Every 4 weeks 
• Weeks 25+: At least every 8 weeks 
• End of Study visit: 22 weeks after the last dose of BIVV020 
Number of participants: 
Approximately 12 participants will be enrolled. Since there is no statistical hypothesis to be tested 
in this study, the sample size is not determined statistically.  
Intervention groups and duration: 
All participants will receive the study intervention. 
Study intervention: BIVV020 
Investigational medicinal product: 
• Formulation: BIVV020 supplied in single use vials containing 750 mg (150 mg/mL; 
extractable volume of 5 mL) 
• Routes of administration: IV loading dose; SC maintenance administration 
• Dose regimen: 50 mg/kg IV loading dose, followed by 600 mg SC weekly  
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Noninvestigational medicinal product: Not applicable 
Devices: Not applicable 
Posttrial access to study medication:  
Participants will continue to receive BIVV020 until the last participant enrolled has completed 
52 weeks of treatment. After that time, a long-term extension study may be available for 
participants to continue to receive BIVV020. 
• Interim analysis 
An interim analysis will be conducted when approximately 12 participants have each been 
treated for 15 weeks.  
• Primary endpoint 
The proportion (and number) of responders fulfilling the criteria in the primary endpoint 
will be presented; the 95% confidence interval for the proportion of responders will be 
estimated with Clopper-Pearson method.  
• Secondary endpoints 
All secondary endpoints will be summarized using descriptive statistics. For categorical 
endpoints, number and proportion of participants will be presented; for continuous 
endpoints, mean, standard deviation, median, and other appropriate statistics will be 
presented; for time-to-event endpoints, Kaplan-Meier methods will be used to estimate 
median time-to-event.  
Data Monitoring/Other committee:Yes 
This study will have a Study Monitoring Committee, comprising at least 2 investigators 
participating in the study and Sponsor representatives. 
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1.2 
SCHEMA  
 
Figure 1 - Graphical study design  
 
D = Day; EOS = end of study; IV = intravenous; SC = subcutaneous 
 
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j 
Height at screening only. 
k To be performed at Weeks 8 and 12 only. 
l 
In addition to the IMP being dispensed in the clinic, the IMP may be dispensed for home administration via DTP services, except if prohibited by local regulatory authorities.  
m Injections will be administered by site staff at visits that occur during Weeks 1 to 5. Participants will perform the injection in the clinic on Week 6 under the supervision of study staff.  
n At visits that occurs from Week 7 onward, injections will be performed in the clinic by the participants, under the supervision of study staff.  
o See Section 8.2.2. 
p See Section 8.2.1. Ad-hoc physical exams may be performed at the discretion of the Investigator based on any AEs reported by the participant. 
q See Section 10.2 for a list of tests to be performed. Labs should be performed prior to drug administration.  
r 
To be performed at Week 24 only. 
s See Section 8.2.7. 
t 
Participants will record IMP administrations in a paper or e-diary when performing administrations at home. 
u Phone calls will be performed to remind participants to take their injections, answer any questions they may have regarding the injections, and to assess AEs. From Weeks 7 to 24, phone calls will be performed on 
weeks that the participants are not seen in the clinic (Weeks 7, 9, 11, 13 to 15, 17 to 19, and 21 to 23). After Week 25, phone calls will be performed approximately 4 weeks after each previous visit. (If a visit during 
this period occurs within approximately 4 weeks of the prior visit, a phone call is not necessary.) Phone calls should continue to occur approximately every 8 weeks after the cessation of treatment, until the EOS 
visit. 
v To be performed prior to drug administration unless otherwise noted. 
w Platelet count should not be performed as a separate test at visits when a complete blood count is performed.  
x If participant provided consent for future research. 
y To be performed at Week 12 only. 
z Participants with positive ADA titers at the last visit of the treatment period will continue to have ADA titers drawn every 8 weeks until titers are decreasing, or until the EOS visit. 
Abbreviations: Ab: antibody; ADA: antidrug antibodies; AE: adverse event; D: day; DTP: Direct-to-Patient; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOS: End of Study; FSH: follicle 
stimulating hormone, HIV: human immunodeficiency virus; HB: hepatitis B; HCV: hepatitis C virus; Ig: immunoglobulin; IMP: investigational medicinal product; IV: intravenous; PD: pharmacodynamics; 
SARS CoV-2: severe acute respiratory syndrome coronavirus 2; SC: subcutaneous; SLE: systemic lupus erythematosus; WOCBP: Women of childbearing potential. 
 
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2 
INTRODUCTION  
BIVV020 is a humanized monoclonal antibody that binds to and selectively inhibits the activated 
form of human serine protease C1s. BIVV020 is a second generation classical complement 
inhibitor with a modified mechanism of action compared to its predecessor, sutimlimab in ITP, 
which binds to the non-activated and activated conformations of C1s. Due to the lower 
concentration of activated C1s compared to total C1s, BIVV020 is not expected to be cleared 
rapidly by target-mediated drug disposition, as is the case for sutimlimab. By selectively targeting 
only the activated conformation of C1s, the clearance of BIVV020 is reduced and its half-life 
prolonged compared to its predecessor. 
The complement system consists of a network of over 30 soluble and membrane-bound plasma 
proteins that upon activation result in an enzymatic cascade responsible for the clearance of 
pathogens and immune complexes (1). Along with subcomponents C1r and C1q, C1s sits at the 
apex of the classical pathway of the complement system. By binding to activated C1s, BIVV020 
prevents enzymatic action of the C1 complex on its substrates, complement factors C4 and C2, 
and thereby blocks formation of the C3 convertase. The result is the inhibition of CP activity 
proximal to C3, which allows the alternative and lectin pathways to remain functionally intact for 
the purpose of host defense. The CP has been implicated in many diseases that are driven by the 
presence of a pathogenic antibody. Immune thrombocytopenia, and particularly ITP that is 
refractory to other treatments, is one such example.  
2.1 
STUDY RATIONALE  
Individuals with ITP who are refractory to current therapies may respond to inhibition of the 
proximal portion of the CP. This hypothesis is supported by data obtained using a first-generation 
CP inhibitor, sutimlimab, which targets the active and inactive conformations of human serine 
protease C1s. The current study will assess the efficacy, safety, and tolerability of a 
second-generation CP inhibitor, BIVV020. BIVV020 selectively targets the activated 
conformation C1s and has a prolonged half-life compared with sutimlimab, allowing for SC 
maintenance administration. 
2.2 
BACKGROUND  
Immune thrombocytopenia is an autoimmune disorder characterized by immunologic destruction 
of platelets in response to an unknown stimulus. Immune thrombocytopenia may be either a 
primary or secondary disorder. Secondary causes of ITP include autoimmune disorders 
(eg, antiphospholipid antibody syndrome), viral infections (eg, human immunodeficiency virus 
[HIV], hepatitis C virus [HCV]), and certain drugs. Decreased platelet levels are caused by 
increased platelet destruction as well as decreased platelet production.  
Patients with ITP are typically first treated with oral corticosteroids and intravenous 
immunoglobulin (IVIg). The goal of treatment is to prevent major bleeding rather than to 
normalize the platelet count. Splenectomy had been recommended for patients who failed initial 
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therapy, although given the long-term risks for infection, this recommendation has recently been 
revisited. Second-line treatment includes azathioprine, cyclosporine A, cyclophosphamide, 
danazol, dapsone, mycophenolate mofetil, rituximab, and thrombopoietin receptor agonists 
(such as eltrombopag and romiplostim). Each agent has potential toxicities including immune 
suppression, secondary malignancies, hypertension, and liver dysfunction. 
Some ITP patients will be refractory or unresponsive to existing therapy, and it has been 
postulated that complement-mediated platelet destruction may play a prominent role in these 
patients. It has been demonstrated that plasma autoantibodies from ITP patients can activate 
complement on the surface of normal human platelets (2, 3). The proportion of ITP patients 
whose samples were capable of activating complement consistently was approximately 50% in 
these studies. The ability of ITP patient autoantibodies to activate complement on the platelet 
surface was significantly inhibited by the specific CP inhibitor TNT003 (a precursor to 
sutimlimab), including inhibition of downstream split products of the classical pathway cascade 
such as C4d and the membrane attack complex C5b-9 (4). Of note, ITP patients with 
autoantibodies capable of activating complement also have reduced platelet production (2, 4). Due 
to the characteristics of complement-mediated activation, currently available therapies for ITP 
would not be expected to be effective in the subset of patients with significant complement-
mediated platelet destruction. For example, complement-opsonized particles and blood cells are 
removed from circulation by the liver, and thus, it would not be expected that splenectomy would 
be effective in this population, similar to observations in other classical complement-mediated 
diseases like cold agglutinin disease (CAD) (5). Therefore, it is likely that a proportion of ITP 
patients, and a substantial proportion of patients with refractory or unresponsive disease, may be 
amenable to therapy with a CP inhibitor such as BIVV020.  
2.3 
BENEFIT/RISK ASSESSMENT  
The human safety risk from short-term inhibition of the complement system in general appears to 
be low, based on the experience with 5 approved products in this therapeutic class. Long-term, 
complement inhibition may increase the risk of infection with encapsulated bacteria, as reflected 
in the product label for eculizumab (Soliris®), an inhibitor of the terminal portion of the 
complement system. To mitigate this risk, this study includes an appropriate program of 
prophylactic vaccinations. 
The risks associated with long-term inhibition of the proximal portion of the classical pathway in 
particular are unknown. Theoretically, such inhibition could increase the risk of systemic lupus 
erythematosus (SLE) or circulating immune complexes (CIC) disease due to the role of the C1 
complex in immune complex clearance, as observed in patients with congenital deficiencies of C1 
complex components (C1q, C1s, and C1r). However, pharmacologic inhibition of C1s differs 
from congenital deficiency of the C1 complex because: 1) congenital C1 complex component 
deficiency is commonly associated with second mutations in other immune system genes; 
2) pharmacologic inhibition of C1s enzymatic function in the C1 complex leaves intact the 
non-enzymatic function of C1q, which is important for the opsonization and phagocytic removal 
of apoptotic cells, which protects against autoimmunity; and 3) the phenotype associated with 
life-long, often total absence of C1 complex structure and function is unlikely to be reproduced by 
pharmacologic antagonism of C1 enzymatic function in fully developed adults. Nevertheless, 
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standard clinical biomarkers related to SLE (eg, antibodies to double-stranded DNA [dsDNA]) 
have been incorporated into the study as safety surveillance measures. 
The risk-benefit profile of BIVV020 is supported by nonclinical toxicology studies, data from 
first-in-human (FIH) studies in healthy adult participants, and the BIVV009 clinical development 
experience, including preliminary data from an ongoing Phase 1b study of BIVV009 in chronic 
ITP patients (TDR16218). 
Nonclinical toxicology studies did not reveal any target organs for BIVV020. There were no 
autoimmune findings in a 5-week toxicity study. No binding or cross-reactivity with off-target 
tissues has been observed. No reproductive or developmental toxicology study has been 
performed to date. Listed below are the preclinical studies that support the current BIVV020 
safety profile: 
• Good Laboratory Practice (GLP) 5-week repeat-dose toxicity study (IV and SC) in 
cynomolgus monkeys with a 4-week recovery period 
• GLP 26-week repeat dose toxicity study (IV and SC) in cynomolgus monkeys with an 
8-week recovery period 
• GLP tissue cross-reactivity study in normal human tissues 
• GLP in vitro hemolysis and plasma flocculation study 
Results of the recently completed FIH, randomized, double-blind, placebo-controlled study of the 
safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ascending single and 
repeated doses of BIVV020 in healthy adult participants (TDU16308-TDR16309) demonstrated 
that BIVV020 has an acceptable safety and tolerability profile while providing dose-dependent 
inhibition of CP activity in healthy adult participants. 
• No deaths, treatment-emergent serious adverse events (TESAEs) or treatment-emergent 
severe AEs were reported. Stopping criteria were not met by any participant or cohort. 
There were no events of serious hypersensitivity and/or anaphylaxis, meningococcal 
infection, SLE. Preliminary review noted no trend or dose relationship in laboratory data, 
vital signs, or electrocardiogram (ECG) parameters.  
• Two AEs of special interest (AESIs), meeting AESI criteria of alanine aminotransferase 
(ALT) ≥2 x upper limit of normal (ULN) were reported: 
- 
An AESI of rhabdomyolysis was reported in 1 subject 7 days after BIVV020 600 mg 
SC dose (peak creatine phosphokinase = 215 × ULN) and assessed as related to study 
drug (TDU16308). The subject performed hot yoga and consumed alcohol 2 days prior 
to the event. The event resolved 15 days later without any corrective intervention. 
Of note, one non-serious AE of rhabdomyolysis in upper arms due to heavy exertion 
was also reported in another subject from the placebo cohort (peak creatine 
kinase = 78.5 × ULN, peak aspartate aminotransferase (AST) = 6.1 × ULN, 
peak ALT = 1.7 × ULN). 
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- 
An AESI of hepatic steatosis (peak ALT value 218 U/l, ULN: 52) was reported in 
1 subject after receiving 4 weekly doses of 300 mg SC BIVV020 on Day 55. The event 
was assessed as related to study drug and resolved 92 days later without any corrective 
intervention (TDR16309). 
Another Sanofi C1s inhibitor, BIVV009, is currently in Phase 3 development for complement 
mediated diseases, including CAD. BIVV009 is being studied in patients with ITP. As of 11 July 
2019, an estimated 162 participants (96 healthy volunteers and 34 patients with CAD as well as 
32 patients with other complement-mediated disorders, including ITP as of 11 April 2019) have 
been exposed to BIVV009 in the clinical development program. BIVV009 appeared to be 
generally well-tolerated based on the safety data.  
As of 11 July 2019, there were no reports of meningococcal infection, SLE, or newly developed 
autoimmune conditions, serious hypersensitivity and/or anaphylaxis in BIVV009 clinical trials. 
Serious infections have been reported in BIVV009 clinical trials in patients with CAD, including 
streptococcal sepsis (Streptococcus pyogenes), Escherichia coli sepsis, wound infection 
staphylococcal (Staphylococcus aureus and Staphylococcus epidermidis) and pneumonia 
(organism unknown). Overall, the pattern of infections in patients with CAD was consistent with 
an older, often medically complex patient population, including some patients who received 
chronic immunomodulatory therapies. 
As of 21 June 2020, twelve chronic ITP patients were enrolled in the ongoing BIVV009 study 
TDR16218. Clinical response, defined by a platelet count greater than 50 × 109/L measured on 
2 separate occasions more than 7 days apart, was achieved by 50% of participants, and 
thrombocytopenia reoccurred during the washout period at the end of Part A. Platelet levels 
improved again in all patients who qualified for retreatment in Part B to date. 
As of 09 April 2020, 12 ITP patients had received at least 1 dose of sutimlimab in the TDR16218 
study part A, with 6 patients having received at least 20 weeks of sutimlimab treatment in Part A 
and 6 patients continuing into the long-term safety extension study Part B. As of 09 April 2020, 
4 of these patients had completed an additional 65-85 weeks of sutimlimab treatment in 
TDR16218 Part B, with an acceptable safety profile and evidence of a sustained therapeutic 
effect. No new safety concerns were identified with long-term sutimlimab treatment. Four patients 
continued to receive sutimlimab in study TDR16218 as of 29 September 2020. 
Whether inhibition of the proximal portion of the CP may increase the risk of severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. Complement-mediated 
neutralization has been described for many viral infections, with all pathways (classical, 
alternative, and lectin) shown to be involved, depending on the particular virus (6). Thus, the 
effect of CP inhibition on the risk of SARS-CoV-2 infection is unclear. Of note, there is also 
evidence to suggest that complement activation may play a role in the pathogenesis of the disease 
(7). If this is indeed the case, complement pathway inhibition may in fact limit the severe 
manifestations of the disease.  
For participants who transition from sutimlimab to BIVV020, the efficacy of BIVV020 is 
expected to be similar to that of sutimlimab, as both target the same protein, C1s, and inhibit CP. 
While it is expected that patients who responded to sutimlimab will have a similar response to 
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BIVV020, there remains the possibility that the response to BIVV020 may differ from that to 
sutimlimab in some patients. The target-specific and mechanism-related risks are expected to be 
the same for both sutimlimab and BIVV020. Patients who transition from sutimlimab to BIVV020 
will benefit from a decreased burden of drug administration and clinic visits over the course of the 
study, as sutimlimab is administered intravenously every other week.  
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of BIVV020 may be found in the Investigator’s Brochure (IB). 
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2.3.1 Risk assessment  
Table 1 - Risk assessment  
Potential risk of clinical 
significance 
Summary of data/rationale for 
risk 
Mitigation strategy 
Study intervention 
Meningococcal infection 
Based on the functions of the classical 
complement pathway and evidence from 
patients with congenital classical 
complement deficiencies, or treated with 
complement inhibitors, BIVV020 may 
potentially increase risk of meningococcal 
infection as a result of long-term 
complement inhibition.  
BIVV020 FIH healthy participant 
experience: No events of meningococcal 
infection have been reported. 
BIVV009 experience: No reports of 
meningococcal infections in BIVV009 
clinical trials as of 21 Jun 2020. As of 
21 Jun 2020, an estimated 187 participants 
received BIVV009 in the clinical 
development program. 
Participants will be monitored for 
meningococcal infection. The risk of 
meningococcal infection will be 
described in the ICFs. Participants will 
be advised to seek medical attention if 
they develop symptoms concerning for 
meningococcal infection.  
To reduce the risk of infection, 
participants will be required to either 
demonstrate a proof of documented 
vaccination against Neisseria 
meningitidis within 5 years of enrollment 
or comply with the vaccination 
requirement of the protocol 
(see Section 8.2.6 for more details).  
Serious infections with other 
encapsulated bacteria 
Long-term complement inhibition may 
potentially increase the risk of serious 
infections with encapsulated bacteria 
(eg: Streptococcus pneumoniae).  
BIVV020 FIH healthy participant 
experience: No reports of serious infections 
with encapsulated bacteria. 
BIVV009 experience: Serious infections 
have been reported in BIVV009 clinical trials 
in patients with CAD, although not 
necessarily with encapsulated organisms. 
These include streptococcal sepsis 
(Streptococcus pyogenes), Escherichia coli 
sepsis, wound infection staphylococcal 
(Staphylococcus aureus and 
Staphylococcus epidermidis) and 
pneumonia (organism unknown). Overall, 
the pattern of infections in patients with 
CAD was consistent with an older, often 
medically complex patient population, 
including some patients who received 
chronic immunomodulatory therapies. 
Participants will be monitored for 
serious infections with encapsulated 
bacteria. The risk will be described in 
the ICFs. Participants will be advised to 
seek medical attention if they develop 
symptoms concerning for serious 
infections with encapsulated bacteria. 
To reduce the risk of infection, 
participants will be required to either 
demonstrate a proof of documented 
vaccination against encapsulated 
bacteria within 5 years of enrollment or 
comply with the vaccination requirement 
of the protocol (see Section 8.2.6 for 
more details). 
Systemic lupus erythematosus 
Long-term CP inhibition could theoretically 
increase the risk of SLE or CIC disease due 
to the role of the C1 complex in immune 
complex clearance, as seen in patients with 
congenital deficiencies of C1 complex 
components (C1q, C1s, and C1r). BIVV020 
Participants will be monitored for the 
development of SLE, lupus like 
syndrome, or other autoimmune 
diseases. A clinical diagnosis of SLE is 
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Potential risk of clinical 
significance 
Summary of data/rationale for 
risk 
Mitigation strategy 
inhibits the C1s enzymatic function in the 
C1 complex. However, pharmacologic 
inhibition of C1s does not necessarily 
equate to congenital deficiency of the C1 
complex. 
 Preclinical data: No autoimmune 
response (CICC1q; ANAs) was observed in 
a 5-week repeat-dose toxicity study in 
cynomolgus monkeys. 
BIVV020 FIH healthy participant 
experience: No reports of SLE or newly 
developed autoimmune conditions. 
BIVV009 experience: There were no 
reports of SLE or newly developed 
autoimmune conditions in BIVV009 clinical 
trials as of 21 June 2020. As of 21 June 
2020, an estimated 187 participants 
received BIVV009 in the clinical 
development program. 
an exclusion criterion for all BIVV020 
clinical studies. 
During screening an ANA as well as 
other autoimmune antibodies will be 
checked. The Investigator may decide 
to exclude participants from the study 
who appear to be at increased risk for 
autoimmune diseases (aside from ITP). 
The risk of development of SLE will be 
described in the ICFs. A panel of 
standard clinical biomarkers related to 
SLE (eg, antibodies to double-stranded 
DNA [dsDNA]) and to CIC disease 
(eg, measurement of CICs) will be 
performed at a regular interval during 
the study. Participants who develop 
clinical manifestations of SLE or a 
confirmed SLE diagnosis will be 
terminated early. 
Serious hypersensitivity reactions 
and/or anaphylaxis 
Serious hypersensitivity reactions and 
anaphylaxis are potential risks with any 
monoclonal antibody.  
BIVV020 FIH healthy participant 
experience: No reports of serious 
hypersensitivity reactions and/or 
anaphylaxis. 
Participants will be monitored during the 
loading dose infusion of BIVV020 and 
immediately following infusion for any 
evidence of a hypersensitivity reaction 
or anaphylaxis. Additionally, the first 
6 maintenance injections of BIVV020 
will occur in the clinic. If any signs or 
symptoms of an allergic reaction are 
observed during BIVV020 infusion, the 
infusion must be immediately 
discontinued, and the participant treated 
as appropriate. 
Coronavirus disease 2019 
(COVID-19) 
The classical pathway is involved in the 
neutralization of various viruses. Data is 
limited regarding SARS-CoV-2 in particular.  
The need for SARS-CoV-2 testing 
during screening will be determined by 
the Sponsor and the Investigator at 
each site. Participants will be counseled 
to avoid situations that may place them 
at increased risk for COVID-19. If a 
participant is diagnosed with 
SARS-CoV-2 during the study, 
discontinuation of BIVV020 will be 
determined by the Investigator and 
Sponsor. 
Study intervention: Risks associated with IV infusions and SC injections (including self-administered SC injections) 
Abbreviations: ANA = antinuclear antibody; C1s = complement component 1, s subcomponent; CAD = cold agglutinin disease; 
CIC = circulating immune complexes; COVID-19 = coronavirus disease 2019; CP = classical complement pathway; FIH = first-in-human; 
ICF = informed consent form; ITP = immune thrombocytopenia; IV = intravenous; SARS-CoV-2 = Severe acute respiratory syndrome 
coronavirus 2; SC = subcutaneous; SLE = systemic lupus erythematosus 
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2.3.2 Benefit assessment  
Immune thrombocytopenia patients who are refractory to current therapies have substantial 
morbidity associated with their disease, including life-threatening bleeding. Treatment with 
BIVV020 has the potential to improve platelet levels and decrease the risk of bleeding in these 
patients. 
2.3.3 Overall benefit: risk conclusion  
Considering the measures taken to minimize risk to participants in this study, the potential risks 
identified in association with BIVV020 are justified by the anticipated benefits that may be 
afforded to participants with persistent/chronic ITP. 
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3 
OBJECTIVES AND ENDPOINTS  
Table 2 - Objectives and endpoints  
Objectives 
Endpoints 
Primary 
• 
To evaluate the effect of BIVV020 on the 
durability of platelet response in participants 
with persistent/chronic immune 
thrombocytopenia (ITP) 
• 
Naïve participants: Proportion of participants with a 
platelet count ≥50 × 109/L at ≥50% of scheduled visits, 
or for participants with baseline platelet count 
<15 × 109/L, a ≥20 × 109/L increase in platelet count 
from baseline at ≥50% of scheduled visits, without 
receiving rescue ITP therapy, as assessed from Week 3 
to Week 24. 
• 
Participants who previously received sutimlimab: 
Proportion of participants with maintenance of platelet 
count ≥30 × 109/L at ≥50% of scheduled visits, without 
receiving rescue ITP therapy, as assessed from Week 3 
to Week 24. 
Secondary 
• 
To assess the safety and tolerability of 
BIVV020  
• 
Standard clinical and laboratory parameters and adverse 
events 
• 
To assess the pharmacokinetics (PK) of 
BIVV020  
• 
Plasma concentrations of BIVV020 
• 
To assess the response rate of treatment with 
BIVV020  
• 
Response rate at Weeks 24 and 52, defined as a platelet 
count ≥50 × 109/L and a greater than 2-fold increase 
from baseline, measured on 2 occasions at least 7 days 
apart, with the absence of bleeding (bleeding is defined 
as bleeding with a score ≥2 on the WHO bleeding 
scale), and the lack of combination ITP therapy during 
this period. 
• 
To assess the time to response 
• 
Time from baseline to first platelet response, defined as 
greater than or equal to each of the following values: 
50 × 109/L and 100 × 109/L (confirmed by 
2 measurements at least 7 days apart) 
• 
To assess the effect of treatment with BIVV020 
on the requirement for rescue ITP therapy 
• 
Proportion of participants who did not require rescue 
therapy for an acute episode of thrombocytopenia after 
Week 3 
• 
To assess the immunogenicity of BIVV020 
• 
Incidence and titer (if relevant) of anti-BIVV020 
antibodies 
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Objectives 
Endpoints 
Exploratory 
 
3.1 
APPROPRIATENESS OF MEASUREMENTS  
The efficacy endpoints for this study are measures of platelet response and ITP disease severity. 
Regarding the primary endpoint, achieving a platelet count ≥50 × 109/L is known to reduce the 
risk of bleeding; for patients with a baseline platelet count <15 × 109/L, an increase of 
≥20 × 109/L would be considered clinically significant. For patients who previously received 
sutimlimab, the endpoint seeks to demonstrate that a response due to sutimlimab is maintained 
with BIVV020. 
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4 
STUDY DESIGN  
4.1 
OVERALL DESIGN  
• This is a Phase 2a open-label, non-randomized, international, multicenter study to evaluate 
the efficacy, safety, and tolerability of BIVV020 in adults with persistent/chronic primary 
ITP. 
• The study will enroll approximately 12 participants: up to 6 participants who have 
previously received and responded to sutimlimab (BIVV009) in study TDR16218, as well 
as participants who have not previously received sutimlimab. 
• The Screening Period will be up to 56 days. Screening begins from the time of the signing 
of the ICF. For participants receiving sutimlimab in study TDR16218, they may continue 
to receive sutimlimab during screening, until at least 14 days prior to the first dose of 
BIVV020, as duration of the PD effect of sutimlimab is approximately 14 days. This 
period between the final dose of sutimlimab and the first dose of BIVV020 is known as the 
Transition Period. 
• Enrollment in the study occurs when a participant receives the first dose of BIVV020. 
• A loading dose of BIVV020 at 50 mg/kg IV will be administered on Day 1, followed by 
maintenance doses of 600 mg SC weekly starting on Day 8. On Day 1, participants will 
remain in the clinic for at least 4 hours after that start of IMP administration. 
• The 600 mg SC dose will be administered as two 2 mL injections. For the first 5 weeks of 
maintenance therapy, the injections will be performed by the site staff, and participants 
will receive education on self-administration. At Week 6, the participant (or their 
caregiver) will perform the injection under the supervision of the site staff. Participants 
should be observed for 30 minutes after IMP administration for the first 6 SC 
administrations. 
• Starting at Week 7, the injections will be performed by the participant or caregiver at 
home. From Weeks 7 to 12, participant will return to the clinic every other week. At clinic 
visits, participants (or their caregiver) will administer BIVV020 under the supervision of 
the study staff. Participants may request assistance with the injections from the study staff 
during these visits.  
• From Weeks 13 to 24, participants will return every 4 weeks and will self-administer 
BIVV020 under the supervision of study staff at those visits. From Week 25 onward, visits 
will occur at a minimum of every 8 weeks, and participants will continue to 
self-administer BIVV020 under the supervision of the study staff during those visits. 
Clinic visits should be scheduled so that they align as closely as possible with the day the 
participant typically takes BIVV020. 
• If a participant prefers for drug administration to occur at the site instead of his/her home 
at any time during the study, this is acceptable. 
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• Phone calls will be performed during the study for site staff to remind participants to take 
their injections, answer any questions they may have regarding the injections, and to 
assess AEs. From Weeks 7 to 24, phone calls will be performed on weeks that the 
participants are not seen in the clinic (Weeks 7, 9, 11, 13 to 15, 17 to 19, and 21 to 23). 
After Week 25, phone calls will be performed approximately 4 weeks after each previous 
visit. (If a visit during this period occurs within approximately 4 weeks of the prior visit, a 
phone call is not necessary.) Phone calls should continue to occur approximately every 
8 weeks after the cessation of treatment, until the EOS visit. 
• Maintenance injections will continue until the last patient enrolled has completed 
52 weeks of treatment. Therefore, the length of maintenance therapy may vary for each 
participant. The maximum duration of treatment for an individual participant is 104 weeks. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN  
This study is designed to evaluate BIVV020 in patients with persistent/chronic primary ITP. 
These patients have failed prior therapies and have few available treatment options. Patients who 
are currently enrolled in study TDR16218 and have responded to sutimlimab will have the option 
of transitioning to this study. In this study, those patients will be able to receive the study drug 
subcutaneously, as opposed to intravenously, which was the case for sutimlimab. 
For patients transitioning from sutimlimab to BIVV020, the switch to BIVV020 is expected to 
result in a decreased burden of drug administration while maintaining the same efficacy and risk 
profile as sutimlimab. Both BIVV020 and sutimlimab are monoclonal antibodies that target the 
same protein, C1s, and inhibit the classical complement pathway. The major difference between 
the 2 molecules is that BIVV020 has mutations that enhance FcRN binding, leading to an 
improved PK profile versus sutimlimab. In addition, BIVV020 demonstrates high affinity and 
specificity for the active form of C1s, whereas sutimlimab binds to both the inactive and active 
forms. BIVV020 has a high affinity (10-9 M) and specificity for the active form of human C1s, 
and is a potent (IC50 = 10-8 M) and complete (100%) inhibitor of serum classical complement 
pathway activity, but not alternative or lectin pathway activity. The active form of C1s is required 
for the progression of the classical complement pathway. BIVV020 binds only this form, thereby 
requiring a lower dose compared to sutimlimab. BIVV020 demonstrates these improvements over 
sutimlimab, while inhibiting the classical complement pathway in effectively the same manner. 
Thus, patients who responded to sutimlimab are expected to have a similar response to BIVV020.  
Participant convenience was taken into consideration in the design of this study. At the start of the 
study, the injections will be administered by the study staff. This will ensure that the participants 
are receiving the injections appropriately and will allow them to become familiar with the 
injection procedures. Education on self-administration will also be provided during this time. As 
the study progresses, the injections will be administered to a greater extent at home, which will 
minimize the time spent traveling to the clinic. However, when coming in for clinic visits, the 
participants will self-administer the injections under the supervision of the study staff to ensure 
that the administrations are being performed correctly.  
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The maximum duration of treatment for an individual participant is 104 weeks. As of 
29 September 2020, 4 ITP patients have received sutimlimab for approximately 2 years with 
maintained efficacy and an acceptable safety profile. No new safety concerns associated with 
long-term sutimlimab treatment have been identified. 
Platelet levels, which constitute the primary efficacy endpoint of the study, are a direct measure of 
disease activity. 
4.2.1 Participant input into design  
Participants were not involved in the design of the study. Nonetheless, this study has a reduced 
visit burden compared to the study from which some of the participants will be enrolled, 
TDR16218. 
4.3 
JUSTIFICATION FOR DOSE  
The dose level and dosing regimen proposed for this study were derived from modeling and 
simulation based on data 
 
. A population PK/PD model was developed using 
 
 and BIVV020 systemic exposure. The initial IV loading 
dose of 50 mg/kg, and the subsequent maintenance dose of 600 mg SC once weekly, were chosen 
to 
.  
The proposed 600 mg once weekly SC dose is 
 
 
 
.  
The selected loading dose of 50 mg/kg 
 
 
. 
4.4 
END OF STUDY DEFINITION  
The end of the study is defined as the date of the last visit of the last participant in the study. 
A participant is considered to have completed the study if he/she has completed all phases of the 
study including the EOS visit.  
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5 
STUDY POPULATION  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
INCLUSION CRITERIA  
Participants are eligible to be included in the study only if all the following criteria apply: 
Age 
I 01. Male and female participants ≥18 years of age at the time of signing the informed consent. 
Type of participant and disease characteristics 
I 02. Confirmed diagnosis of primary ITP; for participants who previously received sutimlimab 
in study TDR16218, a response to sutimlimab must have been obtained, as defined by 
platelet count ≥30 × 109/L on 2 visits at least 7 days apart. 
I 03. For participants who have not previously received sutimlimab: persistent/chronic ITP (ITP 
lasting for ≥6 months) and all the following conditions: 
a) Platelet count ≤30 × 109/L on 2 occasions at least 5 days apart during the Screening 
Period; 
b) Lack of an adequate platelet count response (as defined by maintenance of sustained 
platelet count ≥30 × 109/L in the absence of bleeding) to at least 2 ITP treatments, 1 of 
which was a thrombopoietin receptor agonist.  Other ITP treatments include: IVIg, 
anti-D immunoglobulin, corticosteroids, splenectomy, rituximab, cyclophosphamide, 
azathioprine, danazol, cyclosporin A, mycophenolate mofetil, or fostamatinib. 
c) If receiving weekly thrombopoietin receptor agonist dosing, the last dose must have 
been administered ≥7 days before the first dose of BIVV020. If receiving daily 
thrombopoietin receptor agonist dosing, the last dose must have been administered 
≥24 hours before the first dose of BIVV020. 
d) If applicable, concurrent administration of ITP medications (eg, corticosteroids, IVIg, 
azathioprine, danazol, cyclosporin A, mycophenolate mofetil, or thrombopoietin 
receptor agonists) is acceptable provided the patient has been on a stable dose for at 
least 1 month. See Section 6.8 for additional details. 
e) If previously dosed with rituximab, the last dose of rituximab must have been 
administered at least 12 weeks before the first dose of BIVV020. 
f) If previously dosed with cyclophosphamide, the last dose of cyclophosphamide must 
have been administered at least 4 weeks before the first dose of BIVV020. 
I 04. Documented vaccinations against encapsulated bacterial pathogens (Neisseria 
meningitidis, including serogroup B where available, Haemophilus influenzae, and 
Streptococcus pneumoniae) within 5 years of enrollment, or as specified in Section 8.2.6. 
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 Contraception 
I 05. All contraceptives use by men and women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
- 
Male participants must be surgically sterile for at least 90 days or agree when sexually 
active with female partners of childbearing potential to use a male condom with 
spermicide for the duration of the study and for 52 weeks after the last dose of 
BIVV020. Additionally, sperm donation is not allowed during the study and for 
52 weeks after the last dose of BIVV020. 
- 
Female participants must be post-menopausal, surgically sterile, or be established on 
(≥3 months prior to screening) and agree to continue to use the same highly effective 
method of birth control in conjunction with male barrier contraception (eg, male 
condom with spermicide) during their participation in the study and for 52 weeks after 
the last dose of BIVV020. Highly effective methods of contraception include 
intrauterine device (IUD; Mirena®), established use of oral, implanted, or transdermal 
hormonal method of contraception associated with inhibition of ovulation, bilateral 
tubal ligation, or permanent birth control via the Essure procedure. Participants who 
practice true abstinence, because of the participant’s lifestyle choice (ie, the participant 
should not become abstinent just for the purpose of study participation) are exempt 
from contraceptive requirements. Periodic abstinence (eg, calendar, ovulation, 
symptothermal, postovulation methods) and withdrawal are NOT acceptable methods 
of contraception. Additionally, ova donation is not allowed during the study and for 
52 weeks after the last dose of BIVV020.  
Informed Consent 
I 06. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) of 
the protocol which includes compliance with the requirements and restrictions listed in the 
ICF and in this protocol.  
5.2 
EXCLUSION CRITERIA   
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
E 01. Clinically significant medical history or ongoing chronic illness that would jeopardize the 
safety of the participant or compromise the quality of the data derived from his/her 
participation in the study. 
E 02. Clinically relevant infection within the month prior to enrollment. 
E 03. History of venous or arterial thrombosis within the year prior to enrollment. 
E 04. Clinical diagnosis of SLE. 
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E 05. Secondary ITP from any cause including lymphoma, chronic lymphocytic leukemia, and 
drug-induced thrombocytopenia. 
E 06. Positive hepatitis B surface antigen (HBsAg) or active HCV infection. For patients with an 
isolated positive anti-HBc antibody, hepatitis B virus (HBV) DNA by polymerase chain 
reaction (PCR) must be negative at Screening. Patients who have undergone hepatitis C 
antiviral therapy may be enrolled if they are documented to be HCV RNA negative on at 
least 2 occasions separated by at least 3 months (including 1 RNA test at least 6 months 
after completion of antiviral therapy) and are also HCV RNA negative at Screening. 
E 07. HIV infection. 
E 08. Positive SARS-CoV-2 molecular test (if coronavirus disease [COVID-19] testing required). 
Note: Participants switching from sutimlimab may be enrolled even with a positive 
SARS-CoV-2 test, as per the judgement of the Investigator. 
E 09. Pregnant or lactating women. 
E 10. Eastern Cooperative Oncology Group (ECOG) performance status >2. 
E 11. Sensitivity to any of the study interventions, or components thereof, or other allergy that, 
in the opinion of the Investigator, compromises participation in the study. 
Prior/concomitant therapy 
E 12. Use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), or anticoagulants within 
1 week prior to enrollment. 
Prior/concurrent clinical study experience 
E 13. Concurrent treatment with other experimental drugs or participation in another clinical trial 
with any investigational drug (with the exclusion of sutimlimab) within 30 days or 
5 half-lives, whichever is greater, prior to enrollment.  
Diagnostic assessments 
E 14. Hemoglobin level <10 g/dL. 
E 15. White blood cells (WBCs) or neutrophil counts outside of normal limits, if considered 
clinically significant by the Investigator. Elevated WBC/absolute neutrophil count (ANC) 
attributed to steroid treatment is acceptable. 
E 16. Prothrombin time/international normalized ratio (PT/INR) or activated partial 
thromboplastin time (aPTT) outside of the normal limits, if considered clinically 
significant by the Investigator. 
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Other exclusions 
E 17. Individuals accommodated in an institution because of regulatory or legal order; prisoners 
or participants who are legally institutionalized. 
E 18. Participants not suitable for participation, whatever the reason, as judged by the 
Investigator, including medical or clinical conditions, or participants potentially at risk of 
noncompliance to study procedures. 
E 19. Participants who are employees of the clinical study site or other individuals directly 
involved in the conduct of the study, or immediate family members of such individuals 
(in conjunction with Section 1.61 of the International Council for Harmonisation - Good 
Clinical Practice (ICH-GCP Ordinance E6). 
E 20. Any specific situation during study implementation/course that may raise ethics 
considerations. 
 
5.3 
LIFESTYLE CONSIDERATIONS  
Not applicable.  
5.4 
SCREEN FAILURES  
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently enrolled. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure reasons, eligibility criteria, 
and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failures) may be 
rescreened.  
5.5 
CRITERIA FOR TEMPORARILY DELAYING ENROLLMENT/STUDY INTERVENTION 
ADMINISTRATION  
During a regional or national emergency declared by a governmental agency, if the site is unable 
to adequately follow protocol mandated procedures, contingency measures are proposed in 
Appendix 9 (Section 10.9) and should be considered for screening/enrollment/administration of 
study intervention. 
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6 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY  
Study intervention is defined as any investigational intervention(s), marketed product(s), placebo, 
or medical device(s) intended to be administered to a study participant according to the study 
protocol. 
6.1 
STUDY INTERVENTION(S) ADMINISTERED  
Table 3 - Overview of study interventions administered  
Intervention label 
BIVV020 
Intervention name 
BIVV020, humanized anti-C1s monoclonal antibody 
Type 
Drug 
Dose formulation 
BIVV020 supplied in single use vials containing 750 mg 
(150 mg/mL; extractable volume of 5 mL) 
Unit dose strength(s) 
750 mg/5 mL 
Dosage level(s) 
50 mg/kg IV loading dose, followed by 600 mg SC weekly 
Route of administration 
IV loading dose; SC maintenance administration 
Use 
Experimental 
IMP or NIMP 
IMP 
Packaging and labeling 
Details are provided in the Pharmacy Manual. 
Current/Former name(s) or alias(es) 
Not Applicable 
Table 4 - Arms and associated interventions  
Arm name 
BIVV020 
Associated interventions (intervention label[s]) 
Details are provided in the Pharmacy Manual 
An intravenous (IV) loading dose of BIVV020 at 50 mg/kg will be administered on Day 1, and 
will be followed by maintenance doses of 600 mg SC weekly starting on Day 8. For the first 
5 weeks of maintenance therapy, the injections will be performed by the site staff, and participants 
will receive education on self-administration. At Week 6, the participant (or their caregiver) will 
perform the injection under the supervision of the site staff. Starting at Week 7, the injections will 
be performed by the participants or caregiver at home. See Section 4.1 for additional details 
regarding the locations for IMP administration over the course of the study. 
6.1.1 Intravenous loading dose administration  
• The loading dose of BIVV020 at 50 mg/kg IV will be administered on Day 1. 
• Infusion of the BIVV020 IV preparation should be done using a large volume infusion 
pump. 
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• Approximately 50 mL of dosing solution and approximately 60 mL of flush will be 
administered. An infusion pump will be programmed to deliver 90 mL at a rate of 
150 mL/hr. Any excess volume over 90 mL will remain in-line to account for IV dead 
space. The total time for infusion will be approximately 45 minutes.  
• The total time of dose preparation (vial puncture) to completion of administration may not 
exceed 4 hours. 
• Participants will remain in the clinic for at least 4 hours after the start of IMP 
administration. 
• The administration process is to be documented in the source document worksheet or 
within the administration/dosing logs. 
Further details can be found in the Pharmacy Manual.  
6.1.2 Subcutaneous dose administration  
• The 600 mg SC dose will be administered in 2 injections; each injection will be 2 mL. 
• Depending the study visit, SC administration my be performed at the site or by the 
patient/caregiver at home. In case of home administration, a Patient Diary should be used 
to record administration details.  
• The recommended injection sites include: 
- 
Abdomen (except for the 2 inch [~5 cm] radius area around the navel). This is the 
preferred location. 
- 
Top of thighs.  
- 
Outer area of upper arm (by caregivers only). 
• The SC injections should be given consecutively, but may be spaced apart by up to 
30 minutes. A different site for each injection should be used (eg different locations on the 
abdomen). 
• The total time of dose preparation (vial puncture) to completion of administration may not 
exceed 4 hours. 
• Participants should be observed for 30 minutes after IMP administration for the first 6 SC 
administrations. 
Further details can be found in the Pharmacy Manual. 
BIVV020 may be supplied at the site or from the Principal Investigator/site/Sponsor to the 
participant via a Sponsor-approved courier company (direct-to-patient [DTP]) where allowed by 
local regulations and agreed upon by the participant. The participant/Investigator can refuse this 
option. Details are provided in the Pharmacy Manual. 
For a regional or national emergency declared by a governmental agency that results in travel 
restrictions, confinement, or restricted site access, contingency measures are included in 
Appendix 9 (Section 10.9). 
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A complete description of BIVV020 and its proper handling will be provided in the Pharmacy 
Manual available to the clinical site. The appropriate number of kits will be dispensed as 
necessary for the periods between visits (please refer to SoA Section 1.3). Storage conditions and 
use-by-end date (when required by country regulations) are part of the label text.  
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY  
1. The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received. Any discrepancies must be 
reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only authorized 
site staff may administer it at clinic visits. All study intervention stored at the sites must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) area 
in accordance with the labeled storage conditions with access limited to the Investigator 
and authorized site staff. 
3. The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  
Any quality issue noticed with the receipt or use of an IMP (deficiency in condition, appearance, 
pertaining documentation, labeling, expiration date, etc) must be promptly notified to the Sponsor. 
Some deficiencies may be recorded through a complaint procedure (see Section 8.3.7). 
A potential defect in the quality of IMP may be subject to initiation of a recall procedure by the 
Sponsor. In this case, the Investigator will be responsible for promptly addressing any request 
made by the Sponsor, in order to recall the IMP and eliminate potential hazards.  
Under no circumstances will the Investigator supply IMP to a third party (except for DTP 
shipment, for which a courier company has been approved by the Sponsor), allow the IMP to be 
used other than as directed by this clinical trial protocol, or dispose of IMP in any other manner. 
Additional information regarding treatment allocation, preparation and dispensation are available 
in the Pharmacy Manual. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING  
Not applicable. 
6.4 
STUDY INTERVENTION COMPLIANCE  
• IMP accountability: 
- 
Intervention units are returned by the participant at each visit. In case of DTP process, 
the intervention units can be returned by the carrier (if defined in the contract). 
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- 
The Investigator counts the number of vials, etc, remaining in the returned packs, and 
fills in the Intervention Log Form. 
- 
The Investigator records the dosing information on the appropriate page(s) of the case 
report form (CRF).  
- 
The monitor in charge of the study then checks the CRF data by comparing them with 
the IMP which he/she has retrieved and intervention log forms. 
Starting at Week 7, the injections will be performed by the patient or caregiver, either at home or 
in the clinic at scheduled visits. When participants self-administer the study intervention at home, 
they will be provided with a paper diary or e-diary to record their administrations.  
The date and time of each dose administered in the clinic will be recorded in the source 
documents and recorded. The dose of study intervention and study participant identification will 
be confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention. Deviation(s) from the prescribed dosage regimen should be 
recorded. 
A record of the quantity of BIVV020 units dispensed to and administered by each participant must be 
maintained and reconciled with study intervention and compliance records. Intervention start and 
stop dates, including dates for intervention delays and/or dose reductions will also be recorded. 
6.5 
DOSE MODIFICATION  
Not applicable. 
6.6 
CONTINUED ACCESS TO INTERVENTION AFTER THE END OF THE STUDY  
Participants will continue to receive BIVV020 until the last participant enrolled has completed 
52 weeks of treatment. After that time, a long-term extension study may be available for 
participants to continue to receive BIVV020. If a long-term extension study is available, the 
follow up period for this study may not be applicable or may be modified as per the long-term 
extension study. 
6.7 
TREATMENT OF OVERDOSE  
The Sponsor does not recommend specific treatment for an overdose, as there is no specific 
antidote. However, any supportive medical treatment may be administered, based on evaluation 
and clinical findings. 
In the event of an overdose, the Investigator should: 
1. Contact the Sponsor immediately. 
2. Evaluate the participant to determine, in consultation with the Sponsor, whether study 
intervention should be interrupted or whether the dose should be reduced. 
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3. Obtain a plasma sample for PK analysis within 7 days from the date of the last dose of 
study intervention if requested by the Sponsor (determined on a case-by-case basis). 
4. Document appropriately in the CRF. 
6.8 
CONCOMITANT THERAPY  
Any medication or vaccine (including over the counter or prescription medicines, vitamins, and/or 
herbal supplements, and rescue medication) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Vaccinations such as seasonal influenza vaccines and other recommended vaccines and booster 
vaccinations are permitted as per local standard of care, investigator discretion, and local labels. 
Concurrent administration of ITP medications (corticosteroids, IVIg, azathioprine, danazol, 
cyclosporine A, mycophenolate mofetil, or thrombopoietin receptor agonists) is acceptable 
provided the patient has been on a stable dose for at least 1 month. This applies for both new 
patients and patients who were previously receiving sutimlimab in Study TDR16218. 
Corticosteroids, thrombopoietin receptor agonists, and IVIg are permitted, if the follow 
requirements are met:  
A) Corticosteroids: the first dose of BIVV020 may be dosed only ≥4 days after a steroid pulse 
(single dose of >0.5 mg/kg prednisone equivalent or an increase in prednisone equivalent 
dose from prior levels) for acute ITP treatment 
B) Thrombopoietin receptor agonists: If receiving weekly thrombopoietin receptor agonist 
dosing, the last dose must have been administered ≥7 days before the first dose of 
BIVV020. If receiving daily thrombopoietin receptor agonist dosing, the last dose must 
have been administered ≥24 hours before the first dose of BIVV020. Thrombopoietin 
receptor agonists may be restarted by the Investigator if a participant has an insufficient 
response to BIVV020. 
C) Intravenous Ig (IVIg): the first dose of BIVV020 must be dosed ≥1 day after a dose of 
IVIg. A single dose of IVIg is allowed during the study; additional doses after the first 
dose must be approved by the Sponsor. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.8.1 Rescue medicine  
Rescue medicines given for acute episodes of thrombocytopenia/bleeding, such as steroid 
pulse/bolus, thrombopoietin receptor agonists, or platelet transfusion are allowed (see above for 
guidance on IVIg). Additionally, increasing the dose of concomitant ITP medications to prevent 
or treat bleeding due to low platelet counts is allowed and would be considered rescue therapy. 
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7 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL  
  
7.1 
DISCONTINUATION OF STUDY INTERVENTION   
 
7.1.1 Permanent discontinuation  
In rare instances, it may be necessary for a participant to permanently/definitely discontinue the 
study intervention. If this occurs, a new participant may be enrolled to replace the one who was 
discontinued, unless the permanent discontinuation was due to a BIVV020-related adverse reaction or 
safety concern. 
The Investigator/Sponsor must permanently discontinue dosing with BIVV020 in a participant if 
any of the following participant-level stopping rules are met: 
• Pregnancy in a participant while receiving study drug.  
• Change in compliance with inclusion/exclusion criteria that is clinically relevant and 
affects patient’s safety. 
• Intake of non-permitted concomitant medications that might affect participant’s safety or 
study assessments/objectives. 
• An allergic reaction, including an anaphylactic reaction, in association with BIVV020 
administration. 
• SLE or any other immune complex disease. 
• Meningococcal infection. 
• Occurrence of AEs that, in the opinion of Investigator/Sponsor, may jeopardize patient 
safety or data integrity. These include, but are not limited to, abnormal liver tests and 
abnormal QTc, meeting the stopping criteria (see Section 7.1.2, Section 7.1.3, Appendix 6, 
Section 10.6). 
• Lack of efficacy (see Section 7.1.4).  
• Participant misses more than 3 consecutive doses of BIVV020 without Investigator 
approval. If a participant misses 3 consecutive doses and the Investigator believes the 
participant should remain in the study, a protocol for BIVV020 re-initiation may be 
considered, in consultation with the Sponsor. 
Handling of participants after permanent intervention discontinuation 
If study intervention is definitively discontinued, the participant should continue to be followed 
for an additional 22 weeks. The procedures listed for the EOS visit as per the SoA should be 
performed at the final visit. 
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All cases of definitive intervention discontinuation must be recorded by the Investigator in the 
appropriate pages of the electronic case report form (eCRF) when considered as confirmed. 
7.1.2 Liver chemistry stopping criteria  
Discontinuation of study intervention for abnormal liver tests is required by the Investigator when 
a participant meets one of the conditions outlined in the ALT algorithm in Appendix 6 
(Section 10.6) or in the presence of abnormal liver chemistries not meeting protocol-specified 
stopping rules if the Investigator believes that it is in best interest of the participant.  
7.1.3 QTc stopping criteria  
In the event of prolongation of QTc interval (automatic measurement) ≥500 ms or increase from 
baseline >60 ms, confirmed by a manual reading by the Investigator or a physician delegated by 
the Investigator using the Fridericia formula for correcting QT, the participant should be placed 
under supervision in a specialized setting. Investigational medicinal product administration must 
be stopped and appropriate blood samples collected. Subsequent ECG monitoring of the 
participant should then be performed on a regular and clinically responsible basis until the QTc 
interval returns to a safe value as determined by the Investigator in agreement with the Sponsor. 
Investigational medicinal product may be restarted at the discretion of the Investigator 
(in agreement with the Sponsor) once the QTcF returns to a safe value. 
7.1.4 Lack of efficacy (relapse or sustained lack of improvement) stopping criteria  
The study intervention may be discontinued due to a lack of response. Determination for 
treatment discontinuation in this case will be made by the Investigator and Sponsor. 
7.1.5 Thrombocytosis  
BIVV020 should be discontinued if a participant’s platelet count is >450 × 109/L. BIVV020 may 
be restarted when the platelet count is ≤150 × 109/L. The procedure for BIVV020 re-initiation 
must be discussed with the Sponsor prior to re-dosing.  
7.1.6 Temporary discontinuation  
Temporary intervention discontinuation may be considered by the Investigator because of 
suspected AEs or disruption of the clinical trial due to a regional or national emergency declared 
by a governmental agency (described in Appendix 9 [Section 10.9]). For all temporary 
intervention discontinuations, duration should be recorded by the Investigator in the appropriate 
pages of the eCRF. 
If a participant is diagnosed with COVID-19, the decision to temporarily discontinue the study 
treatment will be made by the Sponsor and Investigator. Once the patient is fully recovered, the 
decision to restart treatment will be determined by the Investigator and Sponsor.  
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7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY  
• A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioral or 
compliance reasons. This is expected to be uncommon. 
• At the time of discontinuing from the study, if possible, an early discontinuation visit 
should be conducted, following procedures for the EOS visit (see SoA [Section 1.3]).  
• If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the Investigator must document this in the site study records. 
If participants no longer wish to take the IMP, they will be encouraged to continue to be followed 
for an additional 22 weeks. The Investigators should discuss with them key visits to attend. The 
value of all their study data collected during their continued involvement will be emphasized as 
important to the public health value of the study.  
Participants who withdraw from the study intervention should be explicitly asked about the 
contribution of possible AEs to their decision, and any AE information elicited must be 
documented. 
All study withdrawals should be recorded by the Investigator in the appropriate screens of the 
eCRF and in the participant’s medical records. In the medical record, at least the date of the 
withdrawal and the reason should be documented. 
In addition, a participant may withdraw his/her consent to stop participating in the study. 
Withdrawal of consent for intervention should be distinguished from withdrawal of consent for 
follow-up visits and from withdrawal of consent for non-participant contact follow-up, 
eg, medical record checks. The site should document any case of withdrawal of consent. 
Participants who have withdrawn from the study cannot be reallocated (retreated) in the study. 
Their study identification numbers must not be reused.  
7.3 
LOST TO FOLLOW UP  
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study. 
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• Before a participant is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
• Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants enrolled. Public sources 
may be searched for vital status information. If vital status is determined as deceased, this 
will be documented and the participant will not be considered lost to follow-up. Sponsor 
personnel will not be involved in any attempts to collect vital status information. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 1 
(Section 10.1).  
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8 
STUDY ASSESSMENTS AND PROCEDURES  
• Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol 
waivers or exemptions are not allowed. 
• Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management or from 
Study TDR16218 (if available) and obtained before signing of the ICF may be utilized for 
screening purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA. 
• The maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required, will be within a safe limit for 
human clinical trials as recommended by the local Institutional Review Boards and Ethics 
Committees. Repeat or unscheduled samples may be taken for safety reasons or for 
technical issues with the samples. 
For a regional or national emergency declared by a governmental agency, contingency measures 
are included in Appendix 9 (Section 10.9).  
8.1 
EFFICACY ASSESSMENTS   
Planned time points for all efficacy assessments are provided in the SoA (Section 1.3). The 
primary efficacy endpoint is determined by platelet counts, which will be assessed by a central 
lab. 
8.2 
SAFETY ASSESSMENTS   
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1 Physical examinations  
• A complete physical examination will include, at a minimum, assessments of the skin, 
cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and weight 
will also be measured and recorded. 
• An abbreviated physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
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• Ad-hoc physical exams may be performed at the discretion of the Investigator based on 
any AE reported by the participant and need not be limited to the time points listed in the 
SoA. 
8.2.2 Vital signs  
• Temperature, pulse rate, respiratory rate, and blood pressure will be assessed. 
• Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
• Blood pressure and pulse measurements should be performed sitting and preceded by at 
least 5 minutes of rest for the participant in a quiet setting without distractions 
(eg, television, cell phones). 
• If possible, vital signs should be performed prior to the collection of clinical laboratories. 
8.2.3 Electrocardiograms  
• Twleve-lead ECGs will be obtained at the time points defined in the SoA using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals. The readout should include date, time, participant study ID, signature of the 
research physician, and at least 3 complexes for each lead. This printout will be retained at 
the site. 
• If possible, ECGs should be performed prior to the collection of clinical laboratories. 
8.2.4 Clinical safety laboratory assessments  
• See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and 
the SoA (Section 1.3) for the timing and frequency. These tests will be performed by a 
central lab, except for serum and urine pregnancy tests, which will be performed locally. 
• The Investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE, as per the guidelines in 
Section 10.3.1. The laboratory reports must be filed with the source documents. Abnormal 
laboratory findings associated with the underlying disease are not considered clinically 
significant, unless judged by the Investigator to be more severe than expected for the 
participant’s condition. 
• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study should be repeated until the values return to normal or baseline 
or are no longer considered clinically significant by the Investigator. 
- 
If clinically significant values do not return to normal/baseline within a period of time 
judged reasonable by the Investigator, the etiology should be identified and the 
Sponsor notified. 
- 
All protocol-required laboratory tests, as defined in Appendix 2 (Section 10.2), must 
be conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
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- 
If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the Investigator (eg, SAE or AE or dose 
modification), then the results must be recorded. 
8.2.4.1 Additional testing in case of hypersensitivity/allergic reaction  
If a participant exhibits signs of a hypersensitivity/allergic reaction during study drug administration, 
the study drug should be stopped immediately, and medical treatment provided, as appropriate. 
In case of a suspected anaphylactic reaction, the following labs may be obtained at the discretion 
of the Investigator, and after discussion with the Sponsor: 
• Approximately 30 to 120 minutes after the start of symptoms: blood draw for antidrug 
antibodies (ADA), tryptase, IL-6, plasma histamine, CICs, and complement levels (CH50). 
A follow-up tryptase level should be obtained approximately 8 days following the 
reaction. Further characterization of the ADA response might be performed. 
• 24-hour urine collection for methylhistamine analysis (ideally collection should be started 
within 6 hours of onset of symptoms). 
8.2.4.2 Additional testing in case of suspected rhabdomyolysis  
If a participant exhibits signs or symptoms which may be indicative of rhabdomyolysis during 
study drug administration, including, but not limited to: muscle pain in the extremities or back, 
excessive muscle weakness or trouble moving arms and legs, dark red or brown urine or 
decreased urination, the following labs should be obtained: 
• Serum creatine kinase. 
• Hepatic function panel. 
8.2.5 Pregnancy testing  
Serum and urine pregnancy testing will be performed as per the SoA (Section 1.3) by local labs. 
8.2.6 Vaccinations against encapsulated bacteria  
In the event a participant does not have documented vaccination against encapsulated bacterial 
pathogens (N meningitidis, including serogroup B meningococcus [where available], H influenzae, 
and S pneumoniae) within 5 years prior to enrollment, vaccination must be initiated as early as 
possible during the Screening Period. Vaccination series must be completed as per current regional 
guidelines for patients with persistent complement deficiency, and in accordance with their 
respective labels, as applicable. Where no regional guidelines are available for patients with 
persistent complement deficiency, vaccinations should include meningococcal conjugate, 
meningococcal serogroup B, 13-valent pneumococcal (PCV13), 23-valent pneumococcal (PPSV23), 
and H influenza type b vaccines, where available, and administered as per regional guidelines. 
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All vaccination series should be initiated as early as possible and completed at least 2 weeks prior 
to the first BIVV020 administration. For participants who have not previously received 
pneumococcal vaccines, PCV13 should be given first and PPSV23 at least 8 weeks after the dose 
of PCV13. Participants must be advised that vaccination may not completely prevent infections 
with encapsulated organisms and that they should immediately report fevers or other symptoms 
consistent with acute infection to the Investigator. 
Patients who develop symptoms consistent with an infection due to encapsulated bacterial 
pathogens during the study period will have a blood sample collected to test for confirmation of 
infection. 
8.2.7 Injection site reactions  
Injection site reactions should be documented by the Investigator as per the SoA (Section 1.3). 
These include pain, tenderness, erythema/redness, swelling, induration, and itching. If the 
Investigator considers an injection site reaction an AE, the appropriate source form should be 
completed. 
8.2.8 Phone calls  
Phone calls will be performed during the study for site staff to remind participants to take their 
injections, answer any questions they may have regarding the injections, and to assess AEs. From 
Weeks 7 to 24, phone calls will be performed on weeks that the participants are not seen in the 
clinic (Weeks 7, 9, 11, 13 to15, 17 to 19, and 21 to 23). After Week 25, phone calls will be 
performed approximately 4 weeks after each previous visit. (If a visit during this period occurs 
within approximately 4 weeks of the prior visit, a phone call is not necessary.) Phone calls should 
continue to occur approximately every 8 weeks after the cessation of treatment, until the EOS 
visit. 
8.2.9 Participant diary  
At-home IMP administration will be recorded in a participant diary (paper or e-diary).  
8.3 
ADVERSE EVENTS (AES), SERIOUS ADVERSE EVENTS (SAES) AND OTHER 
SAFETY REPORTING  
The definitions of AEs and SAEs can be found in Appendix 3 (Section 10.3). The definition of 
AESI is provided in Section 8.3.6. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative).  
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up all AEs (see Section 7). 
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The method of recording, evaluating, and assessing causality of AEs and SAEs and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3). 
8.3.1 Time period and frequency for collecting AE and SAE information  
All AEs (serious or nonserious) will be collected from the signing of the ICF until the EOS visit, 
at the time points specified in the SoA (Section 1.3).  
For participants transitioning from the TDR16218 sutimlimab study, additional considerations and 
requirements for AE/SAE reporting are required. All AEs/SAEs that began during the TDR16218 
study that are ongoing at the EOS visit in TDR16218 and at ICF signature in PDY16894 must be 
reported again during the PDY16894 study screening period in the PDY16894 clinical trial 
database as AEs and as per the SAE reporting procedures outlined in Section 10.3.4. A follow-up 
SAE report for study TDR16218 should also be submitted for ongoing SAEs when participants 
sign the ICF for PDY16894.   
New AE/SAEs that begin after ICF signature in the PDY16894 study must be reported per the 
standard AE/SAE reporting procedures in Section 10.3. If the AE/SAE occurred within 9 weeks 
of the last dose of sutimlimab, the event must include an assessment of causality between the 
AE/SAE and sutimlimab. 
All SAEs and AESI will be recorded and reported to the Sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 3 (Section 10.3). 
The Investigator will submit any updated SAE and AESI data to the Sponsor within 24 hours of it 
being available. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the Investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the Investigator must promptly 
notify the Sponsor. 
8.3.2 Method of detecting AEs and SAEs  
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3 Follow-up of AEs and SAEs  
After the initial AE/AESI/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. At the pre-specified study end-date, all SAEs, and AESIs 
(as defined in Section 8.3.6), will be followed until resolution, stabilization, the event is otherwise 
explained, or the participant is lost to follow-up (as defined in Section 7.3). Further information 
on follow-up procedures is provided in Appendix 3 (Section 10.3). 
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8.3.4 Regulatory reporting requirements for SAEs  
• Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB)/Independent Ethics 
Committees (IEC), and Investigators. 
• Serious adverse events that are considered expected will be specified in the IB.  
• Suspected unexpected serious adverse reactions (SUSARs) are reported to regulatory 
authorities, Investigators, and IRBs/IECs as follows: 
- 
For SUSARs that are life-threatening or result in death, reporting is no later than 
7 days after first knowledge by the Sponsor, with all relevant follow-up information 
subsequently reported within an additional 8 days. 
- 
For SUSARs, other than those that are life-threatening or result in death, reporting is 
no later than 15 days after first knowledge by the Sponsor. 
• An Investigator who receives an Investigator safety report describing an SAE, SUSAR, or 
any other specific safety information (eg, summary or listing of SAEs) from the Sponsor 
will review and then file it along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. It is the responsibility of the Sponsor to assess whether an 
event meets the criteria for a SUSAR, and therefore, is expedited to regulatory authorities. 
8.3.5 Pregnancy  
• Details of all pregnancies in female participants and in female partners of male 
participants will be collected after the start of study intervention and until the end of the 
study. 
• If a pregnancy is reported, the Investigator will record pregnancy information on the 
appropriate form and submit it to the Sponsor within 24 hours of learning of the pregnancy 
(after obtaining the appropriate informed consent for female partners of male participants). 
- 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. 
• The participant/pregnant female partner will be followed to determine the outcome of the 
pregnancy. The Investigator will collect follow-up information on the participant/pregnant 
female partner and the neonate and the information will be forwarded to the Sponsor. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the Investigator will be reported to the Sponsor as described in 
Section 8.3.4. While the Investigator is not obligated to actively seek this information in 
former study participants/pregnant female partner, he or she may learn of an SAE through 
spontaneous reporting. 
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• Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention. 
8.3.6 Adverse event of special interest  
Adverse event of special interest 
An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the 
Sponsor’s product or program, for which ongoing monitoring and immediate notification by the 
Investigator to the Sponsor is required. Such events may require further investigation in order to 
characterize and understand them. Adverse events of special interest may be added, modified or 
removed during a study by protocol amendment. 
• Pregnancy  
- 
Pregnancy occurring in a female participant entered in the study or in a female partner 
of a male participant entered in the study. It will be qualified as an SAE only if it 
fulfills one of the seriousness criteria (see Appendix 3 [Section 10.3]). 
- 
In the event of pregnancy in a female participant, IMP should be discontinued.  
- 
Follow-up of the pregnancy in a female participant or in a female partner of a male 
participant is mandatory until the outcome has been determined. 
• Symptomatic overdose (serious or nonserious) with IMP 
- 
An overdose (accidental or intentional) with the IMP is an event suspected by the 
Investigator or spontaneously notified by the participant (not based on systematic vials 
or syringe counts) and defined as at least twice the intended dose within the intended 
therapeutic interval/visits, adjusted according to the tested drug.  
- 
Infusion: increase of at least 30% of the dose to be administered in the specified 
duration or if the dose is administered in less than half the recommended duration of 
administration. 
- 
Of note, asymptomatic overdose is to be reported as a standard AE. 
• QTc ≥500 ms 
• Increase in ALT >3 × ULN (see Appendix 6, Section 10.6) 
• Other project specific AESIs 
- 
Grade 3 or higher allergic reaction per Common Terminology Criteria for Adverse 
Events (CTCAE) Version 5.0 grading or an anaphylactic reaction in association with 
BIVV020 administration. 
- 
Newly diagnosed or potential development of SLE, autoimmune disease or acute flare 
or chronic worsening of underlying autoimmune disease. 
- 
Meningococcal infection. 
- 
Infection due to an encapsulated bacterial organism. 
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8.3.7 Guidelines for reporting product complaints  
Any defect in the IMP must be reported as soon as possible by the Investigator to the monitoring 
team that will complete a product complaint form within required timelines. 
Appropriate information (eg, samples, labels or documents like pictures or photocopies) related to 
product identification and to the potential deficiencies may need to be gathered. The Investigator 
will assess whether or not the quality issue has to be reported together with an AE or SAE. 
8.4 
PHARMACOKINETICS  
8.4.1 Sampling times  
The sampling times for blood collection can be found in the SoA (Section 1.3) 
8.4.2 Sample handling procedure  
Special procedures for collection, storage, and shipment are provided in the laboratory manual. 
8.4.3 Bioanalytical methods  
Details of bioanalytical methods can be found in the laboratory manual. 
8.4.4 Pharmacokinetic parameters  
Plasma concentrations of BIVV020 will be obtained. This data may be included in a population 
PK analysis.  
Pharmacokinetic samples could be used for testing analytical method performance such as 
comparability and incurred sample reproducibility. 
8.5 
GENETICS AND/OR PHARMACOGENOMICS  
Participants may provide consent for future research to be performed utilizing their samples. This 
may include DNA analysis (See Section 8.9 and Section 10.5). 
8.6 
BIOMARKERS  
• Collection of biological samples for biomarker research is also part of this study. The 
following samples for biomarker research are required and will be collected from all 
participants in this study as specified in the SoA (Section 1.3): 
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• Samples will be tested to evaluate their association with the observed clinical responses. 
• In addition, samples will be stored and analysis may be performed on additional 
biomarkers related to the complement pathway to evaluate their association with observed 
clinical responses. 
• Samples may be used for research to develop methods, assays, prognostics and/or 
companion diagnostics related to the mechanism of action of BIVV020. 
• Samples collected for biomarker analyses and their derivatives will be stored for a period 
of up to 5 years after last patient last visit for potential re-analyses.  
8.7 
IMMUNOGENICITY ASSESSMENTS  
Antibodies to BIVV020 will be evaluated in plasma samples collected from all participants 
according to the SoA (Section 1.3). Additionally, plasma samples should also be collected at the 
final visit from participants who discontinued study intervention or were withdrawn from the 
study. These samples will be tested by the Sponsor or Sponsor’s designee. 
Plasma samples will be screened for antibodies binding to BIVV020 and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to BIVV020 and/or further characterize the immunogenicity of BIVV020. 
The detection and characterization of antibodies to BIVV020 will be performed using a validated 
assay method by or under the supervision of the Sponsor. All samples collected for detection of 
antibodies to study intervention will also be evaluated for BIVV020 plasma concentration to 
enable interpretation of the antibody data. Antibodies may be further characterized and/or 
evaluated for their ability to neutralize the activity of the study intervention(s). Samples may be 
stored for a maximum of 5 years (or according to local regulations) following the last participant’s 
last visit, at a facility selected by the Sponsor to enable further analysis of immune responses to 
BIVV020. 
8.8 
HEALTH ECONOMICS OR MEDICAL RESOURCE UTILIZATION AND HEALTH 
ECONOMICS  
Health economics or medical resource utilization and health economics parameters are not 
evaluated in this study. 
8.9 
USE OF BIOLOGICAL SAMPLES AND DATA FOR FUTURE RESEARCH  
Future research may help further the understanding of disease subtypes, disease biology, related 
conditions, drug response and toxicity, and can help identify new drug targets or biomarkers that 
predict participant response to treatment. Therefore, data and biological samples will be stored 
and used for future research when consented to by participants (see Section 10.1.3) unless 
prohibited by local laws or IRBs/IECs (in such case, consent for future use of sample will not be 
included in the local ICF).  
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For participants who consent to the storage and use of their data and remaining and/or extra 
clinical samples, data and samples may be used after the study ends for future research related 
either to the drug, the mechanism of action, and the disease or its associated conditions. Such 
research may include, but is not limited to, performing assessments on DNA, RNA, proteins or 
metabolites. If future research on genetic material is performed, this will also be limited to the 
purpose of addressing research questions related to the drug, the mechanism of action, the disease 
or its associated conditions. 
In the event future research is conducted for other purposes, the study participants will be 
informed of those purposes and will be given means to object to those research projects. 
Data and samples will be used in compliance with the information provided to participants in the 
ICF Part 2 (future research). 
All study participant data and samples will be coded such that no participant direct identifiers will 
be linked to them. Coded data and samples may be transferred to a Sponsor site (or a 
subcontractor site), which may be located outside of the country where the study is conducted. 
The Sponsor adopts safeguards for protecting participant confidentiality and personal data 
(see Section 10.1.4). 
The samples will be stored for a maximum of 15 years after the end of the study. Any samples 
remaining at the end of retention period will be destroyed. If a participant requests destruction of 
his/her samples before the end of the retention period, the Investigator must notify the Sponsor 
(or its contract organization) in writing. In such case, samples will be destroyed and related coded 
data will be anonymized unless otherwise required by applicable laws. 
Study participant coded data will be stored for future research for up to 25 years after the end of 
the study. If data are still considered of important scientific value after this period, coded data 
already available will be anonymized unless otherwise required by applicable laws (the same will 
apply to the data of a study participant who has requested the destruction of his/her samples). 
A participant’s coded data sets provided to researchers for a specific research project will be 
available to the researchers for a maximum of 2 years after the end of their specific project (end of 
project is defined by publication of the results or finalization of the future research project report). 
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9 
STATISTICAL CONSIDERATIONS  
  
9.1 
SAMPLE SIZE DETERMINATION  
Approximately 12 participants will be enrolled to receive the study intervention. Since there is no 
statistical hypothesis to be tested, the sample size is not determined statistically. 
9.2 
POPULATIONS FOR ANALYSES  
The following populations for analyses are defined:  
Table 5 - Populations for analyses  
Population 
Description 
Screened 
All participants who signed the informed consent form (ICF). 
Enrolled 
All participants from the screened population who receive at least 1 dose (full or 
partial) of study intervention. 
Intention to Treat (ITT) 
All participants who receive at least 1 dose (full or partial) of study intervention.  
Safety 
All participants who receive at least 1 dose (full or partial) of study intervention.  
Pharmacokinetic (PK) 
All participants who receive at least 1 dose (full or partial) of study intervention with 
sufficient sample data.  
Pharmacodynamic (PD) 
All participants who receive at least 1 dose (full or partial) of study intervention with 
sufficient sample data to assess PD parameters.  
PK/PD 
All enrolled participants in the PK population with at least 1 time-matched PK/PD 
parameter. 
 
9.3 
STATISTICAL ANALYSES  
The Statistical Analysis Plan (SAP) will include a more technical and detailed description of the 
statistical analyses described in this section. This section is a summary of the planned statistical 
analyses of the most important endpoints including primary and key secondary endpoints. 
9.3.1 General considerations  
• Common definitions of baseline.  
• General methods (eg, how the continuous variables will be summarized). 
The baseline value is defined as the last non-missing assessment before the first dose of study 
drug. 
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Unless otherwise specified, analyses will be performed based on the populations described above; 
safety analysis will be performed based on the safety population; PK, PD, and PK/PD analyses 
will be performed using the respective populations as defined in Section 9.2. 
The observation period will be divided into 3 segments:  
• The pre-treatment period is defined as the period from enrollment up to the first dose of 
study intervention. Demographics, baseline disease characteristics, medical history, and 
prior therapy including prior ITP therapy use will be summarized based on data collected 
in this period.  
• The treatment-emergent (TE) period (or the study treatment period) for efficacy and 
exposure analysis is defined as the period from the first study intervention administration 
to the last study intervention administration +7 days.  
• The safety analysis period is defined as the period from the first study intervention 
administration to the EOS visit. Safety summaries will be based on this period.  
9.3.2 Primary endpoint  
The primary endpoint is described in Section 3. 
The number and proportion of participants meeting the responder criteria will be presented; the 
95% confidence interval of the proportion of responders will be estimated using Clopper-Pearson 
method. Missing data will not be imputed in the statistical analysis. If a patient discontinues study 
treatment prior to Week 3, the patient will be considered as a non-responder. If a patient 
discontinues the study treatment after Week 3 and prior to Week 24, his or her responder status 
will be assessed using the available data between Week 3 and Week 24. 
9.3.3 Secondary endpoints  
The secondary endpoints are described in Section 3.  
For the continuous secondary endpoints (clinical and laboratory parameters, PK parameters), 
summary statistics by visit including sample size, mean and standard deviation, median, minimum 
and maximum will be presented for the actual value and the change from baseline, if applicable.  
For the time-to-event endpoint (ie, time to first platelet response), Kaplan-Meier method will be 
used to estimate the proportion of participants with response at different study day, and the 
median time to response. Participants with no response will be censored at the date of the last 
platelet count assessment.  
For the responder endpoint (ie, participants who did not require rescue therapy for an acute 
thrombocytopenia episode after Week 3), the number and proportion of such participants will be 
presented, along with the 95% confidence interval of the proportion estimated using 
Clopper-Pearson method. 
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9.3.4 Exploratory endpoints  
9.3.5 Safety analysis  
9.3.5.1 Adverse events  
Treatment-emergent adverse events (TEAEs) are AEs that develop after the first study drug 
administration in the safety analysis period. All AEs in the study include TEAEs and AEs that 
develop prior to the first study drug administration and continue into the safety analysis period. 
All deaths in the study will be reported.  
An overall summary table will be provided with numbers and proportions of participants with at 
least one of the following events (not limited to):  
• TEAE and TESAE 
• Related TEAE and TESAE  
• TEAE Grade 3 or higher 
• TEAESI 
• TEAE infection of Grade 3 or higher and TESAE infection 
• Discontinuation of study treatment and/or withdrawal from study due to a TEAE 
• Death 
Additional summaries, including but not limited to, the incidence of TEAEs and TESAEs by 
system organ class (SOC) and preferred term, and by relationship to study intervention.  
9.3.5.2 Laboratory variables and vital signs  
For laboratory parameters, potentially clinically significant abnormality (PCSA) analyses will be 
performed based on the PCSA list currently in effect at Sanofi at the time of the database lock.  
For vital signs, descriptive statistics for results and changes from baseline will be provided for 
each visit during the safety analysis period. the number and percentage of participants with 
potentially clinically significant vital signs will be provided.  
9.3.6 Other analysis  
For a regional or national emergency declared by a governmental agency, contingency measures 
are included in Appendix 9 (Section 10.9).  
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9.4 
INTERIM ANALYSES   
An interim analysis will be performed when approximately 12 patients have each been treated for 
15 weeks. 
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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS  
10.1 
APPENDIX 1: REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS  
10.1.1 Regulatory and ethical considerations  
• This study will be conducted in accordance with the protocol and with the following: 
- 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki (2013) and the applicable amendments and Council for 
International Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines. 
- 
Applicable ICH GCP Guidelines. 
- 
Applicable laws and regulations (eg, data protection law as General Data Protection 
Regulation [GDPR]). 
• The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (eg, advertisements) must be submitted to an IRB/IEC by the Investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
• Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard 
to study participants. 
• The Investigator will be responsible for the following: 
- 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC.  
- 
Determining whether an incidental finding (as per Sanofi policy) should be returned to 
a participant and, if it meets the appropriate criteria, to ensure the finding is returned 
(an incidental finding is a previously undiagnosed medical condition that is discovered 
unintentionally and is unrelated to the aims of the study for which the tests are being 
performed). The following should be considered when determining the return of an 
incidental finding: 
- 
The return of such information to the study participant (and/or his/her designated 
healthcare professional, if so, designated by the participant) is consistent with all 
applicable national, state, or regional laws and regulations in the country where the 
study is being conducted, and 
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- 
The finding reveals a substantial risk of a serious health condition or has 
reproductive importance, AND has analytical validity, AND has clinical validity.  
- 
The participant in a clinical study has the right to opt out of being notified by the 
Investigator of such incidental findings. In the event that the participant has opted 
out of being notified and the finding has consequences for other individuals, 
eg, the finding relates to a communicable disease, Investigators should seek 
independent ethical advice before determining next steps. 
- 
In case the participant has decided to opt out, the Investigator must record in the 
site medical files that she/he does not want to know about such findings. 
- 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
- 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), and all other applicable local 
regulations. 
As applicable, according to Directive 2001/20/EC, the Sponsor will be responsible for obtaining 
approval from the Competent Authorities of the EU Member States and/or Ethics Committees, as 
appropriate, for any amendments to the clinical trial that are deemed as “substantial” (ie, changes 
which are likely to have a significant impact on the safety or physical or mental integrity of the 
clinical trial participants or on the scientific value of the trial) prior to their implementation. 
10.1.2 Financial disclosure  
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.3 Informed consent process  
• The Investigator or his/her representative will explain the nature of the study to the 
participants and answer all questions regarding the study, including what happens to the 
participant when his/her participation ends.  
• Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 
50, local regulations, ICH guidelines, Privacy and Data Protection requirements including 
those of the GDPR and of the French law, Health Insurance Portability and Accountability 
Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center.  
• The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
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• In case of ICF amendment while the participants are still included in the study, they must 
be re-consented to the most current version of the ICF(s).Where participants are not in the 
study anymore, teams in charge of the amendment must define if those participants must 
or not re-consent or be informed of the amendment (eg, if the processing of personal data 
is modified, if the Sponsor changes, etc). 
• A copy of the ICF(s) must be provided to the participant.  
Participants who are rescreened are required to sign a new ICF. 
The ICF contains 2 separate sections that addresses the use for research of participants’ data 
and/or samples (remaining mandatory ones or new extra samples collected for optional research). 
Optional exploratory research must be detailed in the section “Optional tests/procedures” and 
future research is to be defined in Core Study Informed Consent Form (CSICF) Part 2. Each 
option is subject to an independent consent and must be confirmed by ticking a checkbox in 
CSICF Part 3. The Investigator or authorized designee will explain to each participant the 
objectives of the exploratory research and why data and samples are important for future research. 
Participants will be told that they are free to refuse to participate and may withdraw their consent 
at any time and for any reason during the storage period. 
For a regional or national emergency declared by a governmental agency, contingency measures 
are included in Appendix 9 (Section 10.9).  
10.1.4 Data protection  
All personal data collected and/or processed in relation to this study will be handled in 
compliance with all applicable Privacy & Data Protection laws and regulations, including the 
GDPR. The study Sponsor is the Sanofi company responsible for ensuring compliance with this 
matter, when processing data from any individual who may be included in the Sanofi databases, 
including Investigators, nurses, experts, service providers, Ethics Committee members, etc.  
When archiving or processing personal data pertaining to the Investigator and/or to the 
participants, the Sponsor takes all appropriate measures to safeguard and prevent access to this 
data by any unauthorized third party. 
Protection of participant data 
Data collected must be adequate, relevant and not excessive, in relation to the purposes for which 
they are collected. Each category of data must be properly justified and in line with the study 
objective. 
Participant race and ethnicity will be collected in this study because they are required by 
regulatory agencies (eg, on African American population for the FDA or on Japanese population 
for the Pharmaceuticals and Medical Devices Agency in Japan). They will not be collected in the 
countries where this is prohibited by local regulation. 
• Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor or its service providers will be identifiable only 
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by the unique identifier; participant names or any information which would make the 
participant identifiable will not be transferred to the Sponsor.  
• The participant must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with applicable data protection laws. The level of disclosure 
must also be explained to the participant as described in the informed consent.  
• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
• Participants must be informed that their study-related data will be used for the whole “drug 
development program”, ie, for this trial as well as for the following steps necessary for the 
development of the investigational product, including to support negotiations with payers 
and publication of results. 
Protection of data related to professionals involved in the study  
• Personal data (eg, contact details, affiliation(s) details, job title and related professional 
information, role in the study, professional resume, training records) are necessary to 
allow Sanofi to manage involvement in the study and/or the related contractual or 
pre-contractual relationship. They may be communicated to any company of the Sanofi 
group (“Sanofi”) or to Sanofi service providers, where needed. 
• Personal data can be processed for other studies and projects. At any time, objection to 
processing can be made by contacting the Sanofi Data Protection Officer (link available at 
Sanofi.com).  
• In case of refusal to the processing of personal data by or on behalf of Sanofi, it will be 
impossible to involve the professionals in any Sanofi study. In case the professionals have 
already been involved in a Sanofi study, they will not be able to object to the processing of 
their personal data as long as they are required to be processed by applicable regulations. 
The same rule applies in case the professionals are listed on a regulatory agencies 
disqualification list. 
• Personal data can be communicated to the following recipients:  
- 
Personnel within Sanofi or partners or service providers involved in the study,  
- 
Judicial, administrative and regulatory authorities, in order to comply with legal or 
regulatory requirements and/or to respond to specific requests or orders in the 
framework of judicial or administrative procedures. Contact details and identity may 
also be published on public websites in the interest of scientific research transparency. 
• Personal data may be transferred towards entities located outside the Economic European 
Area, in countries where the legislation does not necessarily offer the same level of data 
protection or in countries not recognized by the European Commission as offering an 
adequate level of protection. Those transfers are safeguarded by Sanofi in accordance with 
the requirement of European law including, notably:  
- 
The standard contractual clauses of the European Commission for transfers towards 
our partners and service providers, 
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- 
Sanofi’s Binding Corporate Rules for intra-group transfers.  
• Professionals have the possibility to lodge a complaint with Sanofi leading Supervisory 
Authority, the “Commission Nationale de l’Informatique et des Libertés” (CNIL) or with 
any competent local regulatory authority. 
• Personal data of professionals will be retained by Sanofi for up to thirty (30) years, unless 
further retention is required by applicable regulations. 
• In order to facilitate the maintenance of Investigators personal data, especially if they 
contribute to studies sponsored by several pharmaceuticals companies, Sanofi participates 
in the Shared Investigator Platform (SIP) and in the TransCelerate Investigator Registry 
(IR) project (https://transceleratebiopharmainc.com/initiatives/investigator-registry/). 
Therefore, personal data will be securely shared by Sanofi with other pharmaceutical 
company members of the TransCelerate project. This sharing allows Investigators to keep 
their data up-to-date once for all across pharmaceutical companies participating in the 
project, with the right to object to the transfer of the data to the TransCelerate project.  
• Professionals have the right to request the access to and the rectification of their personal 
data, as well as their erasure (where applicable) by contacting the Sanofi Data Protection 
Officer: Sanofi DPO - 54 rue La Boétie - 75008 PARIS - France (to contact Sanofi by 
email, visit https://www.sanofi.com/en/our-responsibility/sanofi-global-privacy-
policy/contact). 
10.1.5 Review Committees  
Study Monitoring Committee 
The Study Monitoring Committee (SMC) will comprise at least 2 investigators participating in the 
study as well as Sponsor representatives from clinical and pharmacovigilance functions. The SMC 
will meet quarterly to review safety data and can make recommendations about early study 
closure or changes to the conduct of the study.  
Safety Management Team 
Participant safety will be continuously monitored by the Sponsor’s internal safety team, which 
includes safety signal detection, comprehensive cross-functional characterization, and monitoring 
of the product safety profile at any time during the study as per the Internal Sponsor Safety 
Management Team (SMT) charter (BTD-010790). 
All safety data collected will be summarized and reviewed by the Sponsor’s internal safety team 
for agreement of next steps. 
Based on the review of safety data, enrollment in the study may be paused or the study may be 
stopped. 
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10.1.6 Dissemination of clinical study data  
Study participants 
Sanofi shares information about clinical trials and results on publicly accessible websites, based 
on company commitments, international and local legal and regulatory requirements, and other 
clinical trial disclosure commitments established by pharmaceutical industry associations. These 
websites include clinicaltrials.gov, EU clinicaltrialregister (eu.ctr), and sanofi.com, as well as 
some national registries. 
In addition, results from clinical trials in patients are required to be submitted to peer-reviewed 
journals following internal company review for accuracy, fair balance, and intellectual property. 
For those journals that request sharing of the analyzable data sets that are reported in the 
publication, interested researchers are directed to submit their request to 
clinicalstudydatarequest.com. 
Individual participant data and supporting clinical documents are available for request at 
clinicalstudydatarequest.com. While making information available we continue to protect the 
privacy of participants in our clinical trials. Details on data sharing criteria and process for 
requesting access can be found at this web address: clinicalstudydatarequest.com. 
Professionals involved in the study or in the drug development program 
Sanofi may publicly disclose, and communicate to relevant authorities/institutions, the funding, 
including payments and transfers of value, direct or indirect, made to healthcare organizations and 
professionals and/or any direct or indirect advantages and/or any related information or document 
if required by applicable law, by regulation or by a code of conduct such as the “EFPIA Code on 
Disclosure of Transfers of Value from Pharmaceutical Companies to Healthcare Professionals and 
Healthcare Organisations”. 
10.1.7 Data quality assurance  
• All participant data relating to the study will be recorded on printed or eCRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The 
Investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
• Guidance on completion of CRFs will be provided. 
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site monitoring) 
are provided in separate study documents. 
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• The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals 
(eg, Contract Research Organizations). 
• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the Investigator for 25 years after the signature of the final study 
report unless local regulations or institutional policies require a longer retention period. No 
records may be destroyed during the retention period without the written approval of the 
Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor. 
10.1.8 Source documents  
• Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the Investigator’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be 
explained. The Investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available. 
• The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
• Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.9 Study and site start and closure  
First act of recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
Study/Site termination 
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
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The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for study termination by the Sponsor, as well as reasons for the early closure of a study 
site by the Sponsor or Investigator may include but are not limited to: 
• For study termination: 
- 
Information on the product leads to doubt as to the benefit/risk ratio. 
- 
Discontinuation of further study intervention development. 
• For site termination: 
- 
Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines. 
- 
Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the Investigator. 
- 
Total number of participants included earlier than expected. 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
Study hold 
A dosing and enrollment hold will occur if there is >1 participant with a Grade 4 or higher TEAE, 
unless determined to be clearly unrelated to IMP or attributable to an underlying pre-existing 
disease or condition. The hold may be lifted if the benefit/risk ratio of the study is still deemed to 
be favorable by the Study Monitoring Committee and applicable regulatory and ethical bodies. 
10.1.10 
Publication policy  
• The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor 
before submission. This allows the Sponsor to protect proprietary information and to 
provide comments. 
• The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In 
this case, a coordinating Investigator will be designated by mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
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10.2 
APPENDIX 2: CLINICAL LABORATORY TESTS  
• The tests detailed in Table 6 will be performed by the central laboratory unless otherwise 
specified. 
• Local laboratory results are only required in the event that the central laboratory results are 
not available in time for either study intervention administration and/or response 
evaluation. If a local sample is required, it is important that the sample for central analysis 
is obtained at the same time. Additionally, if the local laboratory results are used to make 
either a study intervention decision or response evaluation, the results must be recorded. 
• Additional tests may be performed at any time during the study as deemed necessary by 
the Investigator or required by local regulations. 
• Pregnancy testing (serum and urine) will be performed locally. 
• SARS-CoV-2 testing, if applicable, will be performed through the central lab.  
Table 6 - Protocol-required laboratory tests  
 
Laboratory tests 
Parameters 
Hematology 
 
 
Platelet count 
 
Red blood cell (RBC) count 
 
Hemoglobin 
 
Hematocrit 
 
RBC indices (at minimum): 
 
Mean corpuscular volume (MCV) 
 
Mean corpuscular hemoglobin (MCH) 
 
White blood cell (WBC) count with differential: 
 
WBC 
Neutrophils 
 
Lymphocytes 
 
Monocytes 
 
Eosinophils 
 
Basophils 
Clinical chemistry 
 
 
Blood urea nitrogen (BUN) 
 
Creatinine 
 
Glucose (non-fasting) 
 
Potassium 
 
Sodium 
 
Calcium 
 
Aspartate aminotransferase (AST)/Serum glutamic-oxaloacetic transaminase (SGOT) 
 
Alanine aminotransferase (ALT)/Serum glutamic-pyruvic transaminase (SGPT) 
 
Alkaline phosphatasea 
 
Total and direct bilirubin 
 
Total protein 
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Laboratory tests 
Parameters 
Coagulation 
 
 
Prothrombin time (PT)/international normalized ratio (INR) 
 
Activated partial thromboplastin time (aPTT) 
SLE panel 
 
 
Antinuclear antibody (ANA) 
Double-stranded DNA (dsDNA) 
Anti-La/SSB antibody (SS-B) 
Anti-Ribonucleoprotein antibody (RNP) 
Anti-Smith antibody (Sm) 
Anti-Ro/SSA antibody (SS-A)  
Anti-Scleroderma antibody (SCL-70)  
Anti-Chromatin antibody 
Anti-Jo-1 antibody 
Anti-Centromere B antibody 
Circulating immune complexes (CIC) 
Other 
 
 
Serum creatine kinase (CK) (at Screening only) 
Follicle-stimulating hormone (FSH) (at Screening only, if indicated; see Section 10.4.1) 
 
CH50 
Routine urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Pregnancy testing 
• 
Serum or highly sensitive urine human chorionic gonadotropin (hCG) pregnancy 
test (as needed for women of childbearing potential) will be performed locally 
Other screening tests 
• 
FSH (as needed in women of non-childbearing potential only) 
• 
Serology (human immunodeficiency virus [HIV] antibody, hepatitis B surface 
antigen [HBsAg], hepatitis B core antibody [HBcAb] immunoglobulin [Ig] G and 
IgM, and hepatitis C virus antibody) 
• 
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular test (if 
applicable)  
NOTES: 
a If alkaline phosphatase is elevated, consider fractionating.  
Investigators must document their review of each laboratory safety report. 
10.3 
APPENDIX 3: AES AND SAES: DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING  
10.3.1 Definition of AE  
AE definition 
• An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered related 
to the study intervention. 
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• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention. 
Definition of unsolicited and solicited AE 
• An unsolicited adverse event is an adverse event that was not solicited using a participant 
diary and that is communicated by a participant who has signed the informed consent. 
Unsolicited AEs include serious and non-serious AEs. 
• Potential unsolicited AEs may be medically attended (ie, symptoms or illnesses requiring a 
hospitalisation, or emergency room visit, or visit to/by a health care provider). The 
participants will be instructed to contact the site as soon as possible to report medically 
attended event(s), as well as any events that, though not medically attended, are of the 
participant’s concern. Detailed information about reported unsolicited AEs will be 
collected by qualified site personnel and documented in the participant’s records. 
• Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant will be collected during interview with the participant and by review of 
available medical records at the next visit. 
• Solicited AEs are predefined local (at the injection site) and systemic events for which the 
participant is specifically questioned. 
Events meeting the AE definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, that are considered clinically significant in the 
judgement of the Investigator and are not related to progression of underlying disease. For 
example: 
- 
Symptomatic and/or 
- 
Requiring either corrective treatment or consultation, and/or  
- 
Leading to IMP discontinuation or modification of dosing, and/or  
- 
Fulfilling a seriousness criterion, and/or  
- 
Defined as an AESI 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even though 
it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. 
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• “Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfill the definition of an AE or SAE. 
• The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfill the definition of an AE or SAE.  
Events NOT meeting the AE definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
10.3.2 Definition of SAE  
An SAE is defined as any adverse event that, at any dose: 
a) Results in death 
b) Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c) Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
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d) Results in persistent or significant disability/incapacity 
- 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
- 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e) Is a congenital anomaly/birth defect 
f) Other situations: 
- 
Medical or scientific judgment should be exercised by the Investigator in deciding 
whether SAE reporting is appropriate in other situations such as significant 
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
- 
Note: The following list of medically important events is intended to serve as a 
guideline for determining which condition has to be considered as a medically 
important event. The list is not intended to be exhaustive:  
- 
Intensive treatment in an emergency room or at home for:  
- 
Allergic bronchospasm  
- 
Blood dyscrasias (ie, agranulocytosis, aplastic anemia, bone marrow 
aplasia, myelodysplasia, pancytopenia, etc) 
- 
Convulsions (seizures, epilepsy, epileptic fit, absence, etc)  
- 
Development of drug dependence or drug abuse  
- 
Suicide attempt or any event suggestive of suicidality  
- 
Syncope, loss of consciousness (except if documented as a consequence of 
blood sampling)  
- 
Bullous cutaneous eruptions  
- 
Cancers diagnosed during the study or aggravated during the study (if judged 
as unusual or significant by the Investigator) 
- 
Chronic neurodegenerative diseases (newly diagnosed) or aggravated during 
the study (if judged unusual or significant by the Investigator). 
10.3.3 Recording and follow-up of AE and/or SAE  
AE and SAE recording 
• When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
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• The Investigator will then record all relevant AE/SAE information. 
• It is not acceptable for the Investigator to send photocopies of the participant’s medical 
records to the Sponsor’s representative in lieu of completion of the required form. 
• There may be instances when copies of medical records for certain cases are requested by 
the Sponsor’s representative. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records before 
submission to the Sponsor’s representative. 
• The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of intensity 
Adverse events will be graded according NCI-CTCAE v5 and classified by SOC/preferred term 
according the last available version of the Medical Dictionary for Regulatory Activities 
(MedDRA) dictionary. 
For AEs not included in the NCI CTCAE, the Investigator will be required to assess the intensity 
of the adverse drug/biologic experience using the CTCAE general guideline: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age 
appropriate instrumental activities of daily living. Instrumental activities of daily living 
refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living. Self-care activities of daily living refer to bathing, dressing and 
undressing, feeding self, using the toilet, taking medications and not bedridden. 
• Grade 4: Life-threatening consequences; urgent intervention indicated. 
• Grade 5: Death related to AE. 
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as described 
in the definition of an SAE, NOT when it is rated as severe. 
Assessment of causality 
• The Investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled 
out. 
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• The Investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The Investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment. 
• For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the Investigator has minimal 
information to include in the initial report. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data. 
• The Investigator may change his/her opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Follow-up of AEs and SAEs 
• The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor’s 
representative to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• If a participant dies during participation in the study or during a recognized follow-up 
period, the Investigator will provide the Sponsor with a copy of any post-mortem findings 
including histopathology. 
• New or updated information will be recorded in the originally submitted documents. 
• The Investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information. 
10.3.4 Reporting of SAEs  
SAE reporting to the Sponsor via an electronic data collection tool 
• The primary mechanism for reporting an SAE to the Sponsor’s representative will be the 
electronic data collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data collection 
tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes available. 
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• After the study is completed at a given site, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
off-line, then the site can report this information on a paper SAE form (see next section) or 
to the Sponsor’s representative by telephone. 
SAE reporting to the Sponsor via paper data collection tool 
• Facsimile transmission of the SAE paper data collection tool is the preferred method to 
transmit this information to the Sponsor’s representative. 
• In rare circumstances and in the absence of facsimile equipment, notification by telephone 
is acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service. 
• Initial notification via telephone does not replace the need for the Investigator to complete 
and sign the SAE data collection tool within the designated reporting time frames. 
10.4 
APPENDIX 4: CONTRACEPTIVE AND BARRIER GUIDANCE  
10.4.1 Definitions  
A woman is considered women of childbearing potential (WOCBP) (fertile) from the time of 
menarche until becoming postmenopausal, unless permanently sterile. 
• A postmenopausal state is defined as when a woman has experienced no menses for 
12 consecutive months without an alternative medical cause. 
• A high follicle-stimulating hormone (FSH) level in the postmenopausal range should be 
used to confirm a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT).  
• Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrollment. 
Permanent sterilization methods include: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
• For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), Investigator 
discretion should be applied to determining study entry eligibility. 
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Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
• If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first administration of study intervention, additional evaluation 
should be considered. 
10.4.2 Contraception guidance  
Female participants of childbearing potential are eligible to participate if they agree to use 
a highly effective method of contraception consistently and correctly as described below in 
Table 7. 
Table 7 - Highly effective contraceptive methods  
Highly effective contraceptive methods that are user dependenta 
Failure rate of <1% per year when used consistently and correctly 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation 
- 
(oral, intravaginal, or transdermal) 
• 
Progestogen-only hormone contraception associated with inhibition of ovulation 
- 
(oral or injectable) 
Highly effective methods that are user independenta 
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation  
- 
Intrauterine device (IUD) 
- 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
• 
Essure procedure 
Vasectomized partner 
Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual partner of the 
woman of childbearing potential and the absence of sperm has been confirmed. If not and less than 1 year after 
vasectomy, additional highly effective method of contraception should be used. Spermatogenesis cycle is approximately 
90 days. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during 
the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the participant. 
NOTES: 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with local regulations 
regarding the use of contraceptive methods for participants participating in clinical studies. 
      
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10.5 
APPENDIX 5: GENETICS  
Future use/analysis of DNA 
• Genetic variation may impact a participant’s response to study intervention, susceptibility 
to, and severity and progression of disease. Variable response to study intervention may be 
due to genetic determinants that impact drug absorption, distribution, metabolism, and 
excretion; mechanism of action of the drug; disease etiology; and/or molecular subtype of 
the disease being treated. Therefore, where local regulations and IRB/IEC allow, a blood 
sample will be collected for possible future DNA analysis from consenting participants. 
• While there are no planned DNA analyses in this study, future research related to the 
complement pathway, ITP, and related diseases may use DNA samples collected from this 
study, if the participant provides consent. They may also be used to develop tests/assays 
including diagnostic tests related to complement pathway inhibitors and ITP. Genetic 
research may consist of the analysis of one or more candidate genes or the analysis of 
genetic markers throughout the genome or analysis of the entire genome (as appropriate). 
• The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to BIVV020 or study interventions of this class to understand 
study disease or related conditions. 
• The Sponsor will store the DNA samples in a secure storage space with adequate measures 
to protect confidentiality. 
• The samples will be retained while research on BIVV020 continues but no longer than 
15 years or other period as per local requirements. 
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10.6 
APPENDIX 6: SAFETY: SUGGESTED ACTIONS AND FOLLOW-UP ASSESSMENTS  
 
Neutropenia is to be recorded as an AE only if at least 1 of the criteria listed in the general 
guidelines for reporting AEs in Section 10.3.1 is met. 
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Increase in serum creatinine is to be recorded as an AE only if at least 1 of the criteria listed in the 
general guidelines for reporting AEs in Section 10.3.1 is met. 
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10.7 
APPENDIX 7: AES, ADES, SAES, SADES, USADES AND DEVICE DEFICIENCIES: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, FOLLOW-UP, 
AND REPORTING IN MEDICAL DEVICE STUDIES  
Not applicable. 
10.8 
APPENDIX 8: COUNTRY-SPECIFIC REQUIREMENTS  
Not applicable. 
10.9 
APPENDIX 9: CONTINGENCY MEASURES FOR A REGIONAL OR NATIONAL 
EMERGENCY THAT IS DECLARED BY A GOVERNMENTAL AGENCY  
The following contingencies may be implemented for the duration of the emergency (after 
Sponsor agreement is obtained). 
Study intervention 
If a participant has to stop BIVV020 due to a regional or national emergency (eg, COVID-19), 
re-initiation of the study intervention can only occur once the Investigator has determined, 
according to his/her best judgement, that 1) BIVV020 did not contribute to the occurrence of the 
concerned adverse event and 2) the selection criteria for the study are still met (refer to Section 5). 
Re-initiation of the study intervention will be done under close and appropriate clinical/and or 
laboratory monitoring and in consultation with the Sponsor. 
Study assessments and procedures 
During the emergency, if the site will be unable to adequately follow protocol mandated 
procedures, alternative treatment outside the clinical trial should be proposed, and 
screening/enrollment/administration of study intervention may be temporarily delayed.  
Attempts should be made to perform all assessments in accordance with the approved protocol to 
the extent possible. In case this is not possible due to a temporary disruption caused by an 
emergency, focus should be given to assessments necessary to ensure the safety of participants 
and those important to preserving the main scientific value of the study. 
Procedures to be considered in the event of a regional or national emergency declared by a 
governmental agency: 
• If onsite visits are not possible, remote visits (eg, with home nurses, home health vendor, 
etc) may be planned for the collection of possible safety and/or efficacy data. 
• If onsite visits are not possible, visit windows may be extended for assessment of safety 
and/or efficacy data that cannot be obtained remotely.  
• Use of local clinic or laboratory locations may be allowed when central labs cannot be 
performed due to a government declared national emergency. 
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Statistical analyses 
The impact of the regional or national emergency declared by a governmental agency on study 
conduct will be summarized (eg, study discontinuation or discontinuation/delay/omission of the 
intervention due to the emergency). Any additional analyses and methods required to evaluate the 
impact on efficacy (eg, missing data due to the emergency) and safety will be detailed in the SAP. 
Informed consent 
For a regional or national emergency declared by a governmental agency, contingency procedures 
may be implemented for the duration of the emergency. The participant or their legally authorized 
representative should be verbally informed prior to initiating any changes that are to be 
implemented for the duration of the emergency (eg, study visit delays/treatment extension, use of 
local labs). 
10.10 APPENDIX 10: ABBREVIATIONS  
 
ADA: 
antidrug antibodies 
AE: 
adverse event 
AESI: 
adverse event of special interest 
ALT: 
alanine aminotransferase 
C1s: 
complement component 1, s subcomponent 
CAD: 
cold agglutinin disease 
COVID-19: 
coronavirus disease 2019 
 
 
CRF: 
case report form 
CTCAE: 
Common Terminology Criteria for Adverse Events 
DTP: 
direct to patient 
ECG: 
electrocardiogram 
eCRF: 
electronic case report form 
EOS: 
end of the study 
FIH: 
first-in-human 
GCP: 
Good Clinical Practice 
GDPR: 
General Data Protection Regulation 
GLP: 
Good Laboratory Practice 
HCV: 
hepatitis C virus 
HIV: 
human immunodeficiency virus 
HRT: 
hormonal replacement therapy 
IB: 
investigator's brochure 
ICH: 
International Council for Harmonisation 
IEC: 
Independent Ethics Committee 
IMP: 
investigational medicinal product 
IRB: 
institutional review board 
ITP: 
immune thrombocytopenia 
IV: 
intravenous 
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IVIg: 
intravenous immunoglobulin 
PCSA: 
potentially clinically significant abnormality 
PCV13: 
13-valent pneumococcal 
PD: 
pharmacodynamics 
PK: 
pharmacokinetics 
PPSV23: 
23-valent pneumococcal 
PT: 
prothrombin time 
SAE: 
serious adverse events 
SAP: 
statistical analysis plan 
SARS-CoV-2: 
serious acute respiratory syndrome coronavirus 2 
SC: 
subcutaneous 
SLE: 
systemic lupus erythematosus 
SoA: 
schedule of activities 
SOC: 
system organ class 
SUSAR: 
suspected unexpected serious adverse reactions 
TEAE: 
treatment-emergent adverse event 
TESAE: 
treatment-emergent serious adverse event 
ULN: 
upper limit of normal 
WBC: 
white blodd cells 
 
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10.11 APPENDIX 11: PROTOCOL AMENDMENT HISTORY  
This is the third amendment of the protocol. Changes to the protocol for amended protocol 03 are 
summarized before the Table of Contents.  Changes to the protocol for amended protocols 01 and 
02 are summarized in this section. 
Amended protocol 02 (10 December 2020) 
This amended protocol 02 (Amendment 02) is considered to be substantial based on the criteria 
set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of 
the European Union. 
OVERALL RATIONALE FOR THE AMENDMENT  
Changes in the protocol have been implemented to address requests received from the US Food 
and Drug Administration as well as additional corrections and clarifications. 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of activities 
Pre-dose weight added on Day 1 
Weight needed for loading dose 
1.3 Schedule of activities, 
footnote g; 
8.2.6 Vaccinations against 
encapsulated bacteria 
Titers may not be used in lieu of documentation of prior 
vaccination 
Clear titer cutoffs associated with 
protection do not exist for most of the 
required vaccines 
5.1 Inclusion criteriion I03 
For participants who have not previously received 
sutimlimab, one of their prior treatments must have 
been a thrombopoietin receptor agonist 
US FDA request 
6.8 Concomitant therapy 
Clarification that vaccinations, such as the seasonal 
influezna vaccine, are permitted during the study 
Clarification 
6.8.1 Rescue medicine 
Clarification that a dose increase in a concomitant ITP 
medication is considered rescue therapy 
Clarification 
8.2.4.1 Additional testing in 
case of 
hypersensitivity/allergic 
reaction 
Clarification of testing to be performed in case of 
hypersensitivity/allergic reaction 
Some of the lab tests listed in the 
prior version were difficult to perform 
and of unclear utility 
8.3.1 Time period and 
frequency for collecting AE 
and SAE information 
Additional information for participants transitioning from 
study TDR16218 
For these participants there are 
additional requirements and 
considerations for AE/SAE reporting 
10.1.9 Study and site start 
and closure 
Addition of a dosing and enrollment hold for toxicity 
US FDA request 
10.2 Appendix 2: Clinical 
Laboratory Tests 
Thrombopoietin removed from clinical chemistry panel 
Test not essential for study and 
cannot be performed through the 
central lab 
Throughout 
Additional clarifications and corrections to typography 
and formatting  
Clarification and consistency with 
document standards 
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Amended protocol 01 (08 December 2020) 
Changes for amended protocol 01 (08 December 2020) were considered to be substantial based on 
the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the 
Council of the European Union. 
OVERALL RATIONALE FOR AMENDMENT 01  
Changes in protocol amendment 01 were implemented to address requests received in a Voluntary 
Harmonisation Procedure communication. 
PROTOCOL AMENDMENT 01 SUMMARY OF CHANGES 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis, Overall design; 
1.3 Schedule of activities, footnote e; 
2.3 Benefit/Risk assessment; 4.1 Overall 
design; 4.2 Scientific rationale for study 
design 
Addition of a maximum duration of treatment of 
104 weeks per participant, and also noted long-term 
safety profile for sutimlimab, another compound 
with a similar mechanism of action. 
Added limit as a safety 
measure, and added further 
information to support 
likelihood of long-term 
safety 
1.1 Synopsis, Overall design; 
4.1 Overall design, 6.1.2 Subcutaneous 
dose administration 
Specified that participants should be observed for 
30 minutes after IMP administration for the first 
6 SC administrations 
Additional safety monitoring 
1.1 Synopsis, Data Monitoring/Other 
committee;  
10.1.5 Review Committees 
Added mention of Data Monitoring Committee to 
synopsis, renamed “Data Monitoring Committee” 
subheading as “Study Monitoring Committee,” and 
added a brief description of the Data Monitoring 
Committee, which will include at least 
2 investigators participating in the study 
Increased safety monitoring 
1.3 Schedule of activities; 5.1 Inclusion 
critierion I05 
Male and female participants are now required to 
continue contraception until 52 weeks after the last 
dose of BIVV020. A urine pregnancy test was 
added to the End of Study visit for women of child-
bearing potential. 
Required contraception 
extended due to the 
prolonged half-life of 
BIVV020 
6.1 Study interventions administered 
(new subsections 6.1.2 and 6.1.3 
Additional details for IMP administration added 
Health authority request 
6.2 Preparation/handling/ 
storage/accountability 
Added statement referring to the Pharmacy Manual 
for procedure details  
Clarification 
6.8 Concomitant therapy 
Clarification that thrombopoietin agonists may be 
restarted by the Investigator after BIVV020 
administration if a participant has an insufficient 
response to BIVV020 
Clarification 
new section added: 
7.1.5 Thrombocytosis; subsequent 
subheadings renumbered 
A new section was added to specify that BIVV020 
should be discontinued if platelet counts rise above 
450 x 109/L 
Added guidance for 
thrombocytosis 
10.1.1 Regulatory and ethical 
considerations 
Clarification that the Declaration of Helsinki 
guidelines referenced are the most recent 
guidelines from 2013 
Clarification 
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Section # and Name 
Description of Change 
Brief Rationale 
10.4.2 Contraceptive guidance 
Double-barrier contraception removed as a highly 
effective contraceptive method 
Double barrier contraception 
is not considered to be 
highly effective as per the 
Clinical Trial Facilitation 
Group 
 
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11 
REFERENCES  
1. Sarma JV, Ward PA. The complement system. Cell Tissue Res. 2011;343(1):227-35. 
2. Peerschke EI, Andemariam B, Yin W, Bussel JB. Complement activation on platelets 
correlates with a decrease in circulating immature platelets in patients with immune 
thrombocytopenic purpura. Br J Haematol. 2010;148:638-45. 
3. Najaoui A, Bakchoul T, Stoy J, Bein G, Rummel MJ, Santoso S, et al. Autoantibody-mediated 
complement activation on platelets is a common finding in patients with immune 
thrombocytopenic purpura (ITP). Eur J Haematol. 2012;88:167-74. 
4. Peerschke EI, Panicker S, Bussel J. Classical complement pathway activation in immune 
thrombocytopenia purpura: inhibition by a novel C1s inhibitor. Br J Haematol. 2016;173:942-
5. 
5. Berentsen S. How I manage patients with cold agglutinin disease. Br J Haematol. 
2018;181:320-30. 
6. Agrawal P, Nawadkar R, Ojha H, Kumar J, Sahu A. Complement evasion strategies of 
viruses: An overview. Front Microbiol. 2017;8:1117. 
7. Java A, Apicelli AJ, Liszewski MK, Reilly AC, Atkinson JP, Kim AHJ, et al. The 
complement system in COVID-19: friend and foe? JCI Insight. 2020;5(15):140711. 
 
 
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SAP_001.pdf: 


Statistical Analysis Plan  
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TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ................................................................................................................... 1 
TABLE OF CONTENTS .................................................................................................................................. 2 
LIST OF TABLES ........................................................................................................................................... 4 
VERSION HISTORY ....................................................................................................................................... 5 
1 
INTRODUCTION .............................................................................................................................. 6 
1.1 
STUDY DESIGN .............................................................................................................................. 6 
1.2 
OBJECTIVE AND ENDPOINTS ...................................................................................................... 6 
2 
SAMPLE SIZE DETERMINATION .................................................................................................. 9 
3 
ANALYSIS POPULATIONS .......................................................................................................... 10 
4 
STATISTICAL ANALYSES ........................................................................................................... 11 
4.1 
GENERAL CONSIDERATIONS .................................................................................................... 11 
4.2 
PARTICIPANT DISPOSITIONS ..................................................................................................... 11 
4.3 
PRIMARY ENDPOINT(S) ANALYSIS ............................................................................................ 12 
4.4 
SECONDARY ENDPOINT(S) ANALYSIS ..................................................................................... 13 
4.5 
TERTIARY/EXPLORATORY ENDPOINT(S) ANALYSIS .............................................................. 14 
4.6 
SAFETY ANALYSES ..................................................................................................................... 15 
4.6.1 
Extent of exposure ......................................................................................................................... 15 
4.6.2 
Adverse events .............................................................................................................................. 16 
4.6.3 
Additional safety assessments ....................................................................................................... 19 
4.6.3.1 
Laboratory variables, vital signs and electrocardiograms (ECGs) ................................................. 19 
4.7 
OTHER ANALYSES....................................................................................................................... 20 
4.7.1 
Immunogenicity analyses ............................................................................................................... 21 
4.8 
INTERIM ANALYSES .................................................................................................................... 21 
5 
SUPPORTING DOCUMENTATION .............................................................................................. 22 
5.1 
APPENDIX 1 LIST OF ABBREVIATIONS ..................................................................................... 22 
5.2 
APPENDIX 2 CHANGES TO PROTOCOL-PLANNED ANALYSES ............................................. 23 
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5.3 
APPENDIX 3 DEMOGRAPHICS AND BASELINE CHARACTERISTICS, PRIOR OR 
CONCOMITANT MEDICATIONS .................................................................................................. 23 
5.4 
APPENDIX 4 DATA HANDLING CONVENTIONS ........................................................................ 25 
5.5 
APPENDIX 5 WHO BLEEDING SCALE ........................................................................................ 26 
5.6 
APPENDIX 6 CRITERIA FOR POTENTIALLY CLINICALLY SIGNIFICANT 
ABNORMALITIES .......................................................................................................................... 27 
 
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LIST OF TABLES  
Table 1 - Objectives and endpoints ................................................................................................................. 6 
Table 2 - Populations for analyses ................................................................................................................ 10 
Table 3 - Sorting of AE tables ....................................................................................................................... 17 
Table 4 - Analyses of adverse events ........................................................................................................... 17 
Table 5 - Selections for AESIs ...................................................................................................................... 18 
Table 6 - Analyses window definition ............................................................................................................ 25 
 
 
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VERSION HISTORY  
This statistical analysis plan (SAP) for study PDY16894 is based on the protocol dated 
25-Jan-2021. There are no major changes to the statistical analysis features in this SAP. The first 
participant was enrolled on 15 Feb 2021. The SAP is approved before the first interim analysis is 
conducted.  
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1 
INTRODUCTION  
1.1 
STUDY DESIGN  
This is a Phase 2a, open-label, non-randomized, multicenter study to evaluate the efficacy, safety 
and tolerability of BIVV020 in adults with persistent/chronic primary ITP. 
During the 56-day screening period, prospective participants will have a detailed medical history 
documented, physical evaluations and blood samples (including platelet count) collected.  For 
participants receiving sutimlimab (BIVV009) in study TDR16218, they may continue to receive 
sutimlimab during screening, until at least 14 days prior to the first administration of 
investigational medicinal product (IMP) - BIVV020.  
The study will enroll approximately 12 participants: up to 6 participants who have received and 
responded to sutimlimab (BIVV009) in study TDR16218 (switchers), as well as patients who 
have not previously received sutimlimab (naïve participants).  
A loading dose of BIVV020 at 50 mg/kg intravenous (IV) will be administered on Day 1, 
followed by maintenance doses of 600 mg subcutaneous weekly starting on Day 8 until the last 
participant enrolled has completed 52 weeks of treatment. The maximum duration of treatment for 
a participant is 104 weeks.  
The on-site visits will be conducted weekly from Week 1 to Week 6, biweekly from Week 7 to 
Week 12, every 4 weeks from Week 13 to Week 24, every 8 weeks after Week 24 until the end-
of-study (EOS) visit. Platelet counts will be collected during the on-site visits. 
1.2 
OBJECTIVE AND ENDPOINTS  
Table 1 - Objectives and endpoints  
 
Objectives 
Endpoints 
Primary 
 
 
 
• 
To evaluate the effect of BIVV020 on the 
durability of platelet response in 
participants with persistent/chronic 
immune thrombocytopenia (ITP) 
• 
Naïve participants: Proportion of 
participants with a platelet count ≥50 
× 10^9 /L at ≥50% of scheduled 
visits, or for participants with 
baseline platelet count <15 × 10^9/L, 
a ≥20 × 10^9/L increase in platelet 
count from baseline at ≥50% of 
scheduled visits, without receiving 
rescue ITP therapy, as assessed 
from Week 3 to Week 24 
• 
Participants who previously received 
sutimlimab: Proportion of participants 
with maintenance of platelet count 
≥30 × 10^9 /L at ≥50% of scheduled 
visits, without receiving rescue ITP 
therapy, as assessed from Week 3 
to Week 24. 
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Objectives 
Endpoints 
Secondary 
 
 
 
• 
To assess the safety and tolerability of 
BIVV020 
• 
Standard clinical and laboratory 
parameters and adverse events 
 
• 
To assess the pharmacokinetics (PK) of 
BIVV020 
• 
Plasma concentrations of BIVV020 
 
• 
To assess the response rate of treatment 
with BIVV020 
• 
Response rate at Weeks 24 and 52, 
defined as a platelet count ≥50 × 
10^9 /L and a greater than 2-fold 
increase from baseline, measured on 
2 occasions at least 7 days apart, 
with the absence of bleeding 
(bleeding is defined as bleeding with 
a score ≥2 on the WHO bleeding 
scale), and the lack of combination 
ITP therapy during this period. 
 
• 
To assess the time to response 
• 
Time from baseline to first platelet 
response, defined as greater than or 
equal to each of the following values: 
50 × 10^9 /L and 100 × 10^9 /L 
(confirmed by 2 measurements at 
least 7 days apart) 
 
• 
To assess the effect of treatment with 
BIVV020 on the requirement for rescue 
ITP therapy 
• 
Proportion of participants who did 
not require rescue therapy for an 
acute episode of thrombocytopenia 
after Week 3 
 
• 
To assess the immunogenicity of 
BIVV020 
• 
Incidence and titer (if relevant) of 
anti-BIVV020 antibodies 
Tertiary/exploratory 
 
 
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Objectives 
Endpoints 
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2 
SAMPLE SIZE DETERMINATION  
Approximately 12 participants will be enrolled. Since there is no statistical hypothesis to be tested 
in this study, the sample size is not determined statistically. 
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3 
ANALYSIS POPULATIONS  
The following populations for analyses are defined:  
Table 2 - Populations for analyses  
Population 
Description 
Enrolled 
All participants from screened population who have been allocated to an 
intervention regardless of whether the intervention was received or not. 
Intent-to-treat (ITT) 
All exposed participants.   
Safety  
All enrolled participants who take at least 1 dose (including partial dose) of study 
intervention.  
Pharmacokinetic (PK) 
All enrolled and treated participants (safety population) with at least one post-
baseline PK sample.  
Pharmacodynamic (PD)  
All enrolled and treated participants (safety population) with at least one post-
baseline PD sample. 
ADA 
All enrolled and treated participants (safety population) with at least one post-
baseline ADA sample. 
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4 
STATISTICAL ANALYSES  
Statistical analysis will be performed by Sanofi, using SAS® version 9.3 or higher and, where 
appropriate, additional validated software.  This SAP is based on protocol Version 3, dated 
25 January 2021. 
4.1 
GENERAL CONSIDERATIONS  
In general, continuous data will be summarized using the number of observations available, mean, 
standard deviation (SD), median, (Q1, Q3 if applicable), minimum, and maximum. Categorical 
and ordinal data will be summarized using the count and percentage of participants. 
The baseline value is defined as the last available value before the first IMP administration. For 
participants enrolled but not treated, the baseline value is defined as the last available value before 
enrollment. The baseline value for platelet count is defined as the average of the values before the 
first IMP administration (ie, platelet count collected during the D-56 to D-1 screening period and 
at 0 hour on D1). 
Observation period  
The observation period will be divided into 3 segments:  
• The pre-treatment period (or the screening period) is defined as the period from the 
time of the signing of the informed consent form (ICF) to the first IMP administration.   
• The on-treatment period is defined as the period from the first IMP administration to the 
last IMP administration +7 days.  
• The post-treatment period is defined as the period after the on-treatment period.  
The treatment-emergent (TE) period includes both on-treatment period and post-treatment 
period. 
Analyses of safety will be based on the treatment-emergent period.   
4.2 
PARTICIPANT DISPOSITIONS  
The number (%) of participants included in each of the analysis populations listed in Table 2 will 
be summarized. 
Screen failures are defined as participants who consent to participate in the study but are not 
subsequently enrolled. The number (%) of screen failures and reasons for screen failures will be 
provided in the screened population. 
The number (%) of participants in the following categories will be provided:  
• Enrolled participants 
• Enrolled but not exposed participants  
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• Enrolled and exposed participants 
• Participants who completed 24-week, 52-week, and the entire treatment period. A 
participant is considered as completed 24-week (52-week) treatment period if the 
participant was treated beyond study day 166 (study day 362 for Week 52). 
• Participants who did not complete the 24-week, 52-week, and the entire treatment period 
and main reason for treatment discontinuation  
• Participants who completed the study  
• Participants who did not complete the study and main reason for study discontinuation. 
In addition, the number (%) of participants screened, enrolled, discontinued treatment, 
discontinued study early will be provided by country and site. 
Protocol deviations 
Critical and major protocol deviations (automatic or manual) will be summarized in the enrolled 
population. Participants impacted by coronavirus disease 2019 (Covid-19) will be summarized 
upon data availability, such as discontinuation due to Covid-19, protocol deviation due to Covid-
19, and visit(s) impacted by Covid-19 as collected in eCRF, etc. 
4.3 
PRIMARY ENDPOINT(S) ANALYSIS  
The primary endpoint is the proportions of participants who met the following criteria: 
1. For naïve participants,  
a. a platelet count ≥50 x 10^9/L OR  
b. a ≥20 x 10^9/L increase from baseline if baseline platelet count <15 x 10^9/L  
at ≥50% of scheduled visits from Week 3 to Week 24. 
For switchers, a platelet count >= 30 x 10^9/L at >=50% of scheduled visits from Week 3 
to Week 24.  
 
2. No concomitant ITP therapy from Week 3 to Week 24.  
Concomitant medications are defined in Section 5.3. The ITP therapies will be identified 
by the Sanofi coding group, reviewed by medical, and defined in the programming 
specifications. The ITP therapies include corticosteroids, thrombopoietin receptor 
agonists, intravenous immunoglobulin, anti-D immunoglobulin, rituximab, fostamatinib, 
immunosuppressants (azathioprine, cyclosporin A, mycophenolate mofetil), 
cyclophosphamide, dapsone, danazol. 
The response rate will be summarized for naïve participants, switchers, and total for the ITT along 
with the 95% exact Clopper-Pearson Confidence Interval (CI).  
Platelet counts will be summarized by visit. These plots will also be provided: 
• Individual platelet count profile: line plot of platelet count by visit for each participant  
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• Spaghetti plot platelet count by participant 
• Median platelet count/change from baseline with by visit  
4.4 
SECONDARY ENDPOINT(S) ANALYSIS  
Participants will continue to receive BIVV020 until the last participant enrolled has completed 
52 weeks of treatment. Week 52 is not a scheduled visit and therefore replaced by Week 56 for 
secondary endpoint(s) analysis. All available data up to Week 56 during the on-treatment period 
will be included. 
The key secondary endpoints include: 
The proportion of participants who met the following criteria at Week 24/Week 56: 
1. A platelet count ≥50 x 10^9/L and a greater than 2-fold increase from baseline, measured 
on 2 occasions at least 7 days apart. 
 
2. No bleeding while the platelet counts are maintained above the threshold. Bleeding is 
defined as bleeding with a score >=2 on the World Health Organization (WHO) bleeding 
scale (Section 5.5) collected in the eCRF. 
 
3. No concomitant ITP therapy while the platelet counts are maintained above the threshold. 
The response rate will be summarized at Week 24 and Week 56 separately for the ITT along with 
the 95% exact Clopper-Pearson CI.  
The proportion of participants who did not require rescue ITP therapy after Week 3 (ie, 
Week 3 to Week 24, 56, and the end of on-treatment period) 
The proportion will be summarized at Week 24, Week 56, and the end of on-treatment period 
separately for the ITT along with the 95% exact Clopper-Pearson CI.  
Time from baseline to first platelet response ≥50 x 10^9/L (confirmed by 2 measurements at 
least 7 days apart) during 56 weeks of treatment 
Time from baseline to first platelet response ≥100 x 10^9/L (confirmed by 2 measurements 
at least 7 days apart) during 56 weeks of treatment 
To qualify for the event, both platelet counts have to be ≥50 x 10^9/L (or ≥100 x 10^9/L) and 
collected ≥7 days apart without any platelet count less than the threshold in between. Platelet 
counts collected at unscheduled visits are included.  
Kaplan-Meier estimates will be calculated for time to the first of the two qualifying platelet 
counts. The 25%, median, 75% time to event along with 95% CI will be presented. The Kaplan-
Meier survival curve will be presented. 
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For participants who do not have a platelet response, their time-to-event will be censored:  
• at Week 56 for those treated beyond 56 weeks  
• at Week 57 (1 week after Week 56) for those who prematurely discontinued the treatment 
due to any adverse event (AE) or lack of response before Week 56 
• at the time of treatment discontinuation for those who prematurely discontinued the 
treatment before Week 56 due to reasons other than AE or lack of response. 
4.5 
TERTIARY/EXPLORATORY ENDPOINT(S) ANALYSIS  
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4.6 
SAFETY ANALYSES  
All safety analyses will be performed on the safety population as defined in Section 3, unless 
otherwise specified, using the following common rules: 
• The analysis of the safety variables will be essentially descriptive, and no testing is 
planned.  
• Safety data in participants who do not belong to the safety population (eg, exposed but not 
enrolled) will be provided. 
4.6.1 Extent of exposure  
The extent of IMP exposure will be assessed by the duration of IMP exposure and treatment 
compliance and summarized within the safety population. 
Duration of IMP exposure 
Duration of IMP exposure is defined as last IMP administration date – first IMP administration 
date + 7 days, regardless of unplanned intermittent discontinuations. If the date of the last IMP 
administration is missing, the duration of IMP will be left as missing.  
Duration of IMP exposure will be summarized quantitatively and categorically: 1 to 6, 7 to 12, 13 
to 24, 25 to 56, 57 to 80, and >80 weeks. 
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Additionally, the cumulative duration of treatment exposure (expressed in participant-months) 
will be provided. 
Treatment compliance 
A given administration will be considered noncompliant if the participant did not receive the 
number of administrations as required by the protocol.   
Percentage of treatment compliance for a participant will be defined as the number of 
administrations that the participant was compliant divided by the total number of administrations 
that the participant was planned to take from the first IMP administration up to the actual last IMP 
administration. 
Treatment compliance will be summarized quantitatively and categorically: <80%, 80% to 100%, 
and ≥100%. 
4.6.2 Adverse events  
General common rules for adverse events 
All AEs will be graded according to National cancer institute common terminology for adverse 
events (NCI-CTCAE) and coded to a lower-level term (LLT), preferred term (PT), high-level 
term (HLT), high-level group term (HLGT), and associated primary system organ class (SOC) 
using the MedDRA (MedDRA) currently in effect at Sanofi at the time of the database lock.  
The AEs will be analyzed in the following 2 categories: 
• Pre-treatment AEs: AEs that developed, worsened or became serious during the pre-
treatment period. 
• Treatment-emergent adverse events (TEAEs): AEs that developed, worsened or became 
serious during the treatment-emergent period (including the on-treatment and post-
treatment periods defined in Section 4.1). 
The primary focus of AE reporting will be on TEAEs.  Pre-treatment and post-treatment AEs will 
be described separately.  
An AE with incomplete or missing date/time of onset (occurrence, worsening, or becoming 
serious) will be classified as a TEAE unless there is definitive information to determine it is a pre-
treatment or a treatment-emergent AE.  
If the assessment of the relationship to IMP is missing for an AE, this AE will be assumed as 
related to IMP. If the intensity is missing for 1 of the treatment-emergent occurrences of an AE, 
the intensity will be assumed as the maximal intensity of the other occurrences of the same event. 
If the intensity is missing for all the occurrences, the intensity will be left as missing. 
Multiple occurrences of the same event in the same participant will be counted only once in the 
tables within a treatment phase, using the maximum (worst) grade by treatment phase. Summaries 
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will be provided for all grades combined and for grade ≥3 (including grade 5). Missing grades, if 
any, will be included in the “all grades” category.  
All AEs will be listed. The AEs that occurred after the first IMP administration (BIVV020) and 
within the sutimlimab (BIVV009) safety follow-up period (ie, last administration of BIVV009 + 
63 days) will be flagged and their relationship to BIVV020 and BIVV009 will be presented.  
The AE tables will be sorted as indicated in Table 3.  
Table 3 - Sorting of AE tables  
AE presentation 
Sorting rules 
SOC, HLGT, HLT and PT 
By the internationally agreed SOC order and by alphabetic order of HLGTs, HLTs and PTs.  
SOC and PT 
By the internationally agreed SOC order and decreasing frequency of PTsa 
PT 
By decreasing frequency of PTs 
a The table of all TEAEs presented by SOC and PT will define the presentation order for all other tables (eg, treatment-emergent SAE) 
presented by SOC and PT, unless otherwise specified.   
Analysis of all adverse events 
The overview of TEAE with the details below will be generated: 
• Any TEAE  
• Any grade ≥3 TEAE  
• Any treatment emergent SAE 
• TEAE leading to death 
• Any TEAE leading to permanent intervention discontinuation  
• Any TEAE infection of grade 3 or higher 
• Any TEAE thromboembolic event. 
The AE summaries of Table 4 will be generated with number (%) of participants experiencing at 
least one event. The analyses will be performed for all grades combined and for grades ≥3.  
Table 4 - Analyses of adverse events  
Type of AE 
MedDRA levels 
All TEAE 
Primary SOC, HGLT, HLT and PT 
 
Primary SOC and PT 
 
PT 
Common TEAE (≥5%)  
Primary SOC and PT 
TEAE related to IMP as per Investigator’s judgment 
Primary SOC and PT 
TEAE by maximal intensity 
Primary SOC and PT  
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Type of AE 
MedDRA levels 
Treatment emergent SAE 
Primary SOC and PT 
Treatment emergent SAE related to IMP as per Investigator’s 
judgment 
Primary SOC and PT 
TEAE leading to permanent intervention discontinuation 
Primary SOC and PT 
Pretreatment AE 
Overviewa 
 
Primary SOC and PT 
a Will include the following AE categories: any AEs, any serious AEs, any AEs leading to death, any AEs leading to permanent intervention 
discontinuation 
Analysis of deaths 
A listing of deaths will be provided. 
Analysis of adverse events of special interest (AESIs)  
Adverse events of special interest (AESI) will be selected for analyses as indicated in Table 5. 
Number (%) of participants experiencing at least one event will be provided for each event of 
interest. Tables will be sorted as indicated in Table 3.  
Table 5 - Selections for AESIs  
AESIs  
Selection 
Pregnancy 
e-CRF “Pregnancy” 
Symptomatic overdose (serious or 
nonserious) with IMP 
e-CRF “Overdose” with “Symptomatic overdose” checked "Yes” 
QTc ≥500 ms 
e-CRF 12-lead “ECG” 
Increase in ALT >3 × ULN 
e-CRF “ALT Increase” 
Grade 3 or higher  
anaphylaxis/hypersensitivity reaction per 
Common Terminology Criteria for Adverse 
Events (CTCAE) Version 5.0 grading or an 
anaphylactic reaction in association with 
BIVV020 administration 
e-CRF “Adverse Events” with  
1. 
“Is the event an AESI” checked “Yes” 
2. 
“Category of Adverse Event” checked “Anaphylaxis/Hypersensitivity” 
3. 
Grade 3 or 4 or 5 
4. 
“Relationship to BIVV020” checked “Related” or missing 
Serious autoimmune diseaseb 
e-CRF “Adverse Events” with  
1. 
“Is the event an AESI” checked “Yes” 
2. 
“Category of Adverse Event” checked “Autoimmune Disease” 
3. 
“Serious” checked “Yes” 
Infections Grade 3 or highera 
e-CRF “Adverse Events” with  
1. 
“Is the event an AESI” checked “Yes” 
2. 
“Category of Adverse Event” checked “Infection” 
3. 
“Intensity” checked “Grade 3” or “Grade 4” or “Grade 5” 
a AESI “Meningococcal infection” and “Infection due to an encapsulated bacterial organism” are included in Infection. 
b Newly diagnosed or potential development of SLE, autoimmune disease or acute flare or chronic worsening of underlying autoimmune 
disease  
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4.6.3 Additional safety assessments  
4.6.3.1 Laboratory variables, vital signs and electrocardiograms (ECGs)  
The following laboratory variables, vital signs and electrocardiogram (ECGs) variables will be 
analyzed. They will be converted into standard international units. 
• Hematology:  
- 
Red blood cells and platelets: Red blood cell (RBC) count, Hemoglobin, Hematocrit, 
Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH) 
- 
White blood cell (WBC) count with differential: WBC, Neutrophils, Lymphocytes, 
Monocytes, Eosinophils, Basophils 
•   Clinical chemistry: 
- 
Metabolism: Glucose (non-fasting), Alkaline phosphatase, Total and direct bilirubin, 
Total protein  
- 
Electrolytes: Potassium, Sodium, Calcium  
- 
Renal function: Blood urea nitrogen (BUN), Creatinine 
- 
Liver function: Aspartate aminotransferase (AST)/Serum glutamic-oxaloacetic 
transaminase (SGOT), Alanine aminotransferase (ALT)/Serum glutamic-pyruvic 
transaminase (SGPT)  
• Coagulation: prothrombin time (PT)/international normalized ratio (INR), activated partial 
thromboplastin time (aPTT) 
• Systemic lupus erythematosus (SLE) panel: Antinuclear antibody (ANA), Double-
stranded DNA (dsDNA), Anti-La/SSB antibody (SS-B), Anti-Ribonucleoprotein antibody 
(RNP), Anti-Smith antibody (Sm), Anti-Ro/SSA antibody (SS-A), Anti-Scleroderma 
antibody (SCL-70), Anti-Chromatin antibody, Anti-Jo-1 antibody, Anti-Centromere B 
antibody, Circulating immune complexes (CIC) 
• Urine electrolytes: Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, 
urobilinogen, nitrite, leukocyte esterase by dipstick, Microscopic examination (if blood or 
protein is abnormal) 
• Vital signs: heart rate, systolic and diastolic blood pressure, respiratory rate, temperature 
• ECG variables: heart rate, PR, QRS, QT, and corrected QTc (according to Fridericia).  
Data below the lower limit of quantitation (LLOQ)/detection limit will be replaced by half of the 
LLOQ, data above the upper limit of quantification (ULOQ) will be replaced by ULOQ value. 
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Quantitative analyses 
For all laboratory variables, vital signs and ECG variables above, descriptive statistics for results 
and changes from baseline will be provided for each planned visit, the last value during the on-
treatment period. These analyses will be performed using central measurements only (when 
available) for laboratory variables.  
Analyses according to PCSA  
Potentially clinically significant abnormality (PCSA) analyses will be performed based on the 
PCSA list currently in effect at Sanofi at the time of the database lock (Section 5.6). For 
parameters for which no PCSA criteria are defined, similar analyses will be done using the normal 
range, if applicable. For parameters defined as efficacy endpoints, PCSA summaries will not be 
provided. 
Analyses according to PCSA will be performed based on the worst value during the treatment-
emergent period, using all measurements (either local or central, either scheduled, nonscheduled 
or repeated). 
For laboratory variables, vital signs above, the incidence of participants with at least one PCSA 
during the treatment-emergent period will be summarized regardless of the baseline level and 
according to the following baseline status categories: 
• Normal/missing 
• Abnormal according to PCSA criterion or criteria 
For ECG, the incidence of participants with at least one abnormal ECG during the treatment-
emergent period will be summarized regardless of the baseline level and according to the 
following baseline status categories:  
• Normal/missing 
• Abnormal  
4.7 
OTHER ANALYSES  
BIVV020 concentrations will be described in the PK population for each planned visit (D1 – 0H, 
D1 – 1H, D8, D15, D29, D43, Week 12, Week 24, every 8 weeks starting from D170, 22 weeks 
after the final BIVV020 dose), using the following descriptive statistics: mean, standard deviation, 
geometric mean, coefficient of variation, median, minimum, and maximum. 
All concentration values below the lower limit of quantitation (LLOQ) will be treated as zero in 
all summary statistics excepted for the geometric mean and associated coefficient of variation for 
which they will be considered as missing.  
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4.7.1 Immunogenicity analyses  
Participant’s antidrug antibodies (ADA) status, response variable (see definitions below) will be 
summarized in the ADA population. 
Sample status (negative, positive, inconclusive) and titers will also be described overtime using 
descriptive statistics.  
The impact of positive immune response on efficacy, PK and safety variables may be further 
explored, depending on ADA incidence. 
Participant’s ADA status 
• Participants with pre-existing ADA correspond to participants with ADAs present in 
samples drawn before first IMP administration. Participants with missing ADA sample at 
baseline will be considered as without pre-existing ADA. 
• Participants with treatment-emergent ADA correspond to participants with at least one 
treatment-induced/boosted ADA. 
- 
Participants with treatment-induced ADA correspond to participants with ADAs that 
developed during the treatment-emergent period and without pre-existing ADA 
(including participants without pre-treatment samples). 
- 
Participants with treatment-boosted ADA correspond to participants with pre-existing 
ADAs that are boosted during the treatment-emergent period to a significant higher 
titer than the baseline. A 3-fold serial dilution schema is used during titration, so at 
least a 9-fold increase of titer values will be considered as significant.  
• Participants without treatment-emergent ADA correspond to participants without 
treatment-induced/boosted ADA during the treatment-emergent period. 
• Participants with inconclusive ADA are defined as participants which cannot irrefutably 
be classified as with or without treatment-emergent ADA.  
ADA response variable: 
• ADA incidence is defined as the proportion of participants found to have seroconverted 
(treatment-induced ADAs) or boosted their pre-existing ADA response (treatment-boosted 
ADAs) at any time point during the treatment-emergent period. 
4.8 
INTERIM ANALYSES  
An interim analysis (IA) will be conducted when approximately 12 participants have each 
been treated for 15 weeks. 
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5 
SUPPORTING DOCUMENTATION  
5.1 
APPENDIX 1 LIST OF ABBREVIATIONS  
 
ADA: 
antidrug antibodies 
AE: 
adverse event 
ALT: 
alanine aminotrasferase 
ANA: 
antinuclear antibody 
aPTT: 
activated partial thromboplastin time 
AST: 
aspartate aminotrasferase 
ATC: 
anatomic category, anatomic or therapeutic category 
BMI: 
body mass index 
BUN: 
blood urea nitrogen 
CI: 
Confidence Interval 
CIC: 
circulating immune complexes 
Covid-19: 
coronavirus disease 2019 
 
 
dsDNA: 
double-stranded DNA 
ECG: 
electrocardiogram, electrocardiogram 
eCRF: 
electronic case report form 
EOS: 
end-of-study 
HGLT: 
high level group term 
HLGT: 
high-level group term 
HLT: 
high-level term 
IA: 
interim analysis 
ICF: 
informed consent form 
IMP: 
investigational medicinal product 
INR: 
international normalized ratio 
ITP: 
immune thrombocytopenia 
ITT: 
Intent-to-treat, intent-to-treat 
IV: 
intravenous 
LLOQ: 
lower limit of quantification 
LLT: 
lower-level term 
MCH: 
mean corpuscular hemoglobin 
MCV: 
mean corpuscular volume 
MedDRA: 
medical dictionary for regulatory activities 
NCI-CTCAE: 
National cancer institute common terminology for adverse events, National 
cancer institute common terminology for adverse events 
PCSA: 
potentially clinically significant abnormality, potentially clinically significant 
abnormality 
PD: 
pharmacodynamics 
PK: 
pharmacokinetic 
PT: 
preferred term 
RBC: 
red blood cell 
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RNP: 
Anti-Ribonucleoprotein antibody 
SAP: 
statistical analysis plan 
SCL-70: 
Anti-Scleroderma antibody 
SD: 
standard deviation 
SGOT: 
serum glutamic-oxaloacetic transaminase 
SGPT: 
serum glutamic-pyruvic transaminase 
SLE: 
systemic lupus erythematosus 
Sm: 
Anti-Smith antibody 
SOC: 
system organ class 
SOC: 
system organ class 
SS-A: 
Anti-Ro/SSA antibody 
SS-B: 
Anti-La/SSB antibody 
TE: 
treatment-emergent 
TEAE: 
treatment-emergent adverse event, treatment-emergent adverse event 
ULOQ: 
upper limit of quantification 
WBC: 
white blood cell 
WHO: 
World Health Organization 
WHO-DD: 
World Health Organization - drug dictionary, World Health Organization drug 
dictionary, World Health Organization-drug dictionary 
 
5.2 
APPENDIX 2 CHANGES TO PROTOCOL-PLANNED ANALYSES  
Not applicable. 
5.3 
APPENDIX 3 DEMOGRAPHICS AND BASELINE CHARACTERISTICS, PRIOR OR 
CONCOMITANT MEDICATIONS  
Demographics, baseline characteristics, medical surgical history 
The following demographics and baseline characteristics, medical and surgical history will be 
summarized using descriptive statistics in the exposed population. 
Demographic and baseline characteristics  
• age in years as quantitative variable and in categories (<65, ≥65) 
• gender (Male, Female) 
• race (American Indian or Alaska Native, Asian, Black or African American, Native 
Hawaiian or Other Pacific Islander, White, Not Reported, Unknown) 
• ethnicity (Hispanic or Latino, not Hispanic or Latino, Not Reported, Unknown) 
• height (cm), weight (kg), body mass index (BMI) (kg/m^2). 
Baseline safety and efficacy parameters (apart from those listed above) will be presented along 
with the safety and efficacy summaries.  
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The time (in years) from the date of ITP diagnosis to the date of first IMP administration will be 
summarized.  
Medical and surgical history will be coded to a PT and associated primary SOC using the 
MedDRA currently in effect at Sanofi at the time of database lock.  
The proportion of participants who had documented vaccines within 5 years and who have 
received vaccination during the study will be summarized. The vaccines include meningococcal 
vaccine, S. pneumoniae vaccine, and H. influenza vaccine. The type of the vaccine will be 
summarized. 
Prior or concomitant medications 
All medications will be coded using the World Health Organization-drug dictionary (WHO-DD) 
using the version currently in effect at Sanofi at the time of database lock.  
• Prior medications are those the participant used prior to first IMP intake.  Prior 
medications can be discontinued before first administration or can be ongoing during 
treatment period. 
• Concomitant medications are any interventions received by the participant concomitantly 
to the IMP during the on-treatment period. 
• Post-treatment medications are those the participant took in the period running from the 
end of the concomitant medications period up to the end of the study.  
• A given medication can be classified as a prior medication and/or as a concomitant 
medication and/or as post-treatment medication. If it cannot be determined whether a 
given medication was taken prior or concomitantly or post, it will be considered as prior, 
concomitant, and post-treatment medication. 
The prior, concomitant, and post-treatment non-ITP medications will be summarized for the ITT 
population, by anatomic and therapeutic level. The summaries will be sorted by decreasing 
frequency of anatomic category (ATC) based on incidence in intervention group. Therapeutic 
classes are sorted by decreasing frequency within each anatomic class. In case of equal frequency, 
alphabetical order will be used. Participants will be counted once in each ATC category (anatomic 
or therapeutic) linked to the medication.  
Prior ITP, concomitant non-rescue ITP, and concomitant rescue ITP therapies/medications will be 
summarized separately by the ATC level 4 chemical class and medication name. All ITP therapies 
will be listed with rescue ITP therapies flagged.  
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5.4 
APPENDIX 4 DATA HANDLING CONVENTIONS  
Study Day 
Study Day is defined as days relative to the date of first IMP administration (ie, D1 as in the 
protocol). The Study Day of an event is calculated as  
• (date of event – date of first IMP administration + 1), if the event is on or after the first 
IMP administration; 
• (date of event – date of first IMP administration), if the event is prior to the first IMP 
administration. 
The date of the first IMP administration is Study Day 1. 
Analysis windows for time points 
The following analysis windows will decide how the scheduled and/or unscheduled visits will be 
used in the by-visit analyses of efficacy, safety, PK and ADA variables. 
A measurement (scheduled or unscheduled) will be used if it is available and measurement date is 
within the analysis window.   
After applying these time windows, if multiple assessments are associated to the same time point, 
the closest from the targeted study day will be used. If the difference is a tie, the value after the 
targeted study day will be used. If multiple valid values exist within a same day, then the first 
value of the day will be selected.  
If there is no measurement for a given parameter in an analysis window, data will be considered 
missing for the corresponding visit.  
Table 6 - Analyses window definition  
Scheduled visit post baseline 
Targeted study day 
D1 
1 
D4 
4 (+/-1) 
D8 
8 (+/-1) 
 
D15 
15 (+/-1) 
 
D22 
22 (+/-1) 
D29 
29 (+/-1) 
 
D36 
36 (+/-1) 
 
D43 
43 (+/-1) 
 
Week 8 
57 (+/-2) 
 
Week 10 
80 (+/-2) 
 
Week 12 
85 (+/-2) 
 
Week 16 
113 (+/-3) 
 
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Scheduled visit post baseline 
Targeted study day 
Week 20 
141 (+/-3) 
 
Week 24 
169 (+/-4) 
 
Week 32 
171 (+/-4) 
 
Week 40 
281 (+/-4) 
 
Every other 2 weeks until the until the 
last participant enrolled has completed 
52 weeks of treatment 
 
 
Study days are calculated considering Day 1 as the day of first administration of intervention (or the day of randomization for participant not 
exposed). 
Unscheduled visits 
Unscheduled visit measurements of laboratory data, vital signs, ECG and ADA will be used for 
computation of baseline, the last on-treatment value, analysis according to PCSAs, and the shift 
summaries for safety. They will also be included in the by-visit summaries if they are re-allocated 
to scheduled visits. 
5.5 
APPENDIX 5 WHO BLEEDING SCALE  
Coded Grade of Bleeding 
Decoded Grade of Bleeding 
1 
Petechiae 
2 
Mild blood loss 
3 
Gross blood loss 
4 
Debilitating blood loss 
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5.6 
APPENDIX 6 CRITERIA FOR POTENTIALLY CLINICALLY SIGNIFICANT 
ABNORMALITIES   
CRITERIA for POTENTIALLY CLINICALLY SIGNIFICANT ABNORMALITIES 
Parameter 
PCSA 
Comments 
Clinical Chemistry 
ALT 
By distribution analysis : 
>3 ULN 
>5 ULN 
>10 ULN 
>20 ULN 
Enzymes activities must be expressed in ULN, not in 
IU/L.  
Concept paper on DILI – FDA draft Guidance 
Oct 2007. 
Internal DILI WG Oct 2008. 
Categories are cumulative. 
First row is mandatory. Rows following one mentioning 
zero can be deleted. 
AST 
By distribution analysis : 
>3 ULN 
>5 ULN 
>10 ULN 
>20 ULN 
Enzymes activities must be expressed in ULN, not in 
IU/L.  
Concept paper on DILI – FDA draft Guidance 
Oct 2007. 
Internal DILI WG Oct 2008. 
Categories are cumulative. 
First row is mandatory. Rows following one mentioning 
zero can be deleted. 
Alkaline 
Phosphatase 
>1.5 ULN 
Enzymes activities must be expressed in ULN, not in 
IU/L. 
Concept paper on DILI – FDA draft Guidance 
Oct 2007. 
Internal DILI WG Oct 2008. 
Total Bilirubin 
>1.5 ULN 
>2 ULN 
Must be expressed in ULN, not in µmol/L or mg/L. 
Categories are cumulative. 
Concept paper on DILI – FDA draft Guidance 
Oct 2007. 
Internal DILI WG Oct 2008. 
Conjugated Bilirubin >35% Total Bilirubin and TBILI>1.5 ULN 
Conjugated bilirubin dosed on a case-by-case basis. 
ALT and Total 
Bilirubin 
ALT>3 ULN and TBILI>2 ULN 
Concept paper on DILI – FDA draft Guidance 
Oct 2007. 
Internal DILI WG Oct 2008. 
To be counted within a same treatment phase, 
whatever the interval between measurement. 
CPK 
>3 ULN 
>10 ULN 
FDA Feb 2005. 
Am J Cardiol April 2006. 
Categories are cumulative. 
First row is mandatory. Rows following one mentioning 
zero can be deleted. 
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CRITERIA for POTENTIALLY CLINICALLY SIGNIFICANT ABNORMALITIES 
Parameter 
PCSA 
Comments 
CLcr (mL/min) 
(Estimated 
creatinine clearance 
based on the 
Cokcroft-Gault 
equation)  
<15 (end stage renal disease) 
≥15 - <30 (severe decrease in GFR) 
≥30 - < 60 (moderate decrease in GFR) 
≥60 - <90 (mild decrease in GFR) 
≥ 90 (normal GFR) 
FDA draft Guidance 2010 
Pharmacokinetics in patients with impaired renal 
function-study design, data analysis, and impact on 
dosing and labeling 
eGFR 
(mL/min/1.73m2) 
(Estimate of GFR 
based on an MDRD 
equation)  
 
<15 (end stage renal disease) 
≥15 - <30 (severe decrease in GFR) 
≥30 - < 60 (moderate decrease in GFR) 
≥60 - <90 (mild decrease in GFR) 
≥ 90 (normal GFR) 
FDA draft Guidance 2010 
Pharmacokinetics in patients with impaired renal 
function-study design, data analysis, and impact on 
dosing and labeling 
Creatinine 
≥150 μmol/L (Adults) 
≥30% change from baseline 
≥100% change from baseline 
Benichou C., 1994. 
 
Uric Acid 
Hyperuricemia  
Hypouricemia  
 
>408 μmol/L 
<120 μmol/L  
Harrison- Principles of internal Medicine 17th Ed., 2008. 
Blood Urea Nitrogen ≥17 mmol/L 
 
Chloride 
<80 mmol/L 
>115 mmol/L 
 
Sodium 
≤129 mmol/L 
≥160 mmol/L 
 
Potassium 
<3 mmol/L 
≥5.5 mmol/L 
FDA Feb 2005. 
Total Cholesterol 
≥7.74 mmol/L  
Threshold for therapeutic intervention. 
Triglycerides 
≥4.6 mmol/L 
Threshold for therapeutic intervention. 
Lipasemia 
≥3 ULN 
 
Amylasemia 
≥3 ULN 
 
Glucose 
Hypoglycaemia 
Hyperglycaemia 
 
≤3.9 mmol/L and <LLN 
≥11.1 mmol/L (unfasted); ≥7 mmol/L (fasted) 
 
ADA May 2005. 
ADA Jan 2008. 
HbA1c 
>8% 
 
Albumin 
≤25 g/L 
 
CRP 
>2 ULN or >10 mg/L (if ULN not provided) 
 FDA Sept 2005. 
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CRITERIA for POTENTIALLY CLINICALLY SIGNIFICANT ABNORMALITIES 
Parameter 
PCSA 
Comments 
Hematology 
WBC 
<3.0 Giga/L (Non-Black); <2.0 Giga/L (Black) 
≥16.0 Giga/L 
Increase in WBC: not relevant. 
To be interpreted only if no differential count available. 
Lymphocytes 
>4.0 Giga/L 
 
Neutrophils 
<1.5 Giga/L (Non-Black);<1.0 Giga/L (Black) 
International Consensus meeting on drug-induced 
blood cytopenias, 1991. 
FDA criteria. 
Monocytes 
>0.7 Giga/L 
 
Basophils 
>0.1 Giga/L 
 
Eosinophils 
>0.5 Giga/L or >ULN (if ULN≥0.5 Giga/L) 
Harrison- Principles of internal Medicine 17th Ed., 2008. 
Hemoglobin 
≤115 g/L (Male); ≤95 g/L (Female) 
≥185 g/L (Male); ≥165 g/L (Female) 
 
Decrease from Baseline ≥20 g/L 
Criteria based upon decrease from baseline are more 
relevant than based on absolute value. Other 
categories for decrease from baseline can be used 
(≥30 g/L, ≥40 g/L, ≥50 g/L). 
Hematocrit 
≤0.37 v/v (Male) ; ≤0.32 v/v (Female) 
≥0.55 v/v (Male) ; ≥0.5 v/v (Female) 
 
RBC 
≥6 Tera/L 
Unless specifically required for particular drug 
development, the analysis is redundant with that of Hb. 
Otherwise, consider FDA criteria. 
Platelets 
<100 Giga/L 
≥700 Giga/L 
International Consensus meeting on drug-induced 
blood cytopenias, 1991. 
Urinalysis 
pH 
≤4.6 
≥8 
 
Vital signs 
HR 
≤50 bpm and decrease from baseline ≥20 bpm 
≥120 bpm and increase from baseline≥20 bpm 
To be applied for all positions (including missing) 
except STANDING. 
SBP 
≤95 mmHg and decrease from baseline ≥20mmHg 
≥160 mmHg and increase from baseline ≥20 mmHg 
To be applied for all positions (including missing) 
except STANDING. 
DBP 
≤45 mmHg and decrease from baseline ≥10 mmHg 
≥110 mmHg and increase from baseline ≥10 mmHg 
To be applied for all positions (including missing) 
except STANDING. 
Orthostatic 
Hypotension 
Orthostatic SDB 
Orthostatic DBP 
 
 
≤-20 mmHg 
≤-10 mmHg 
 
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CRITERIA for POTENTIALLY CLINICALLY SIGNIFICANT ABNORMALITIES 
Parameter 
PCSA 
Comments 
Weight 
≥5% increase from baseline  
≥5% decrease from baseline 
FDA Feb 2007. 
ECG 
 
Ref.: ICH E14 guidance (2005) and E14 Q&A (2012), 
and Cardiac Safety Research Consortium White Paper 
on PR and QRS (Nada et al. Am Heart J. 2013; 165(4) 
: 489-500) 
HR 
<50 bpm 
<50 bpm and decrease from baseline ≥20 bpm 
<40 bpm 
<40 bpm and decrease from baseline ≥20 bpm 
<30 bpm 
<30 bpm and decrease from baseline ≥20 bpm 
 
>90 bpm 
>90 bpm and increase from baseline ≥20bpm 
>100 bpm  
>100 bpm and increase from baseline ≥20bpm 
>120 bpm  
>120 bpm and increase from baseline ≥20 bpm 
Categories are cumulative 
 
 
 
 
 
 
Categories are cumulative 
 
PR 
>200 ms 
>200 ms and increase from baseline ≥25% 
> 220 ms 
>220 ms and increase from baseline ≥25% 
> 240 ms 
> 240 ms and increase from baseline ≥25% 
Categories are cumulative 
 
QRS 
>110 ms 
>110 msec and increase from baseline ≥25% 
>120 ms 
>120 ms and increase from baseline ≥25% 
Categories are cumulative 
QT 
>500 ms 
 
QTc 
 
Absolute values (ms) 
 
>450 ms 
>480 ms 
>500 ms 
Increase from baseline 
Increase from baseline ]30-60] ms 
Increase from baseline >60 ms 
To be applied to any kind of QT correction formula.  
Absolute values categories are cumulative 
 
QTc >480 ms and QTc >60 ms are the 2 PCSA 
categories to be identified in individual 
subjects/patients listings. 
 
 
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