Clinical trial NCT05132127
Conditions: Cold Agglutinin Disease
Sponsor: Sanofi
Start date: 2021-11-11; Completion date: 2022-11-15
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This was a multi-center, single treatment-group, open-label study to provide sutimlimab to the adult participants with cold agglutinin disease (CAD) who had completed the CARDINAL (NCT number: NCT03347396) or CADENZA (NCT number: NCT03347422) studies and benefitted from sutimlimab treatment in Japan.

• Study and treatment duration: the period between the participant's completion of the CARDINAL and CADENZA studies and sutimlimab or other appropriate CAD therapy becoming commercially available to participants in Japan.

Detailed description:
The period between screening/baseline visit (upon the participant's completion\* of the CARDINAL and CADENZA studies) and end of treatment with sutimlimab in this study was determined by sutimlimab or other appropriate CAD therapy becoming commercially available to participants in Japan.

Arms: arm 1: Participants with body weight greater than or equal to (\>=) 39 kilograms (kg) to less than (\<) 75 kg and who had completed Part B of CARDINAL or CADENZA study were enrolled in the current study and received sutimlimab (BIVV009) 6.5 grams as intravenous (IV) infusion on Day 0, Day 7, Day 21 and thereafter every 2 weeks (maximum duration: 49 weeks) in the current study.
Interventions: intervention 1: sutimlimab
Intervention descriptions: intervention 1: Pharmaceutical form: solution for injection Route of administration: intravenous (IV)

Protocol documents:
Prot_000.pdf: 
Any and all information presented in this document shall be treated as confidential and shall remain the exclusive property of Sanofi (or any of its 
affiliated companies). The use of such confidential information must be restricted to the recipient for the agreed purpose and must not be 
disclosed, published or otherwise communicated to any unauthorized persons, for any reason, in any form whatsoever without the prior written 
consent of Sanofi (or the concerned affiliated company); ‘affiliated company’ means any corporation, partnership or other entity which at the date 
of communication or afterwards (i) controls directly or indirectly Sanofi, (ii) is directly or indirectly controlled by Sanofi, with ‘control’ meaning 
direct or indirect ownership of more than 50% of the capital stock or the voting rights in such corporation, partnership or other entity 
According to Template: Sanofi OneDocument Version 5.1, dated 11-FEB-2021 
Page 1 
CLINICAL TRIAL PROTOCOL 
Protocol title: 
An open-label study for sutimlimab in participants with 
cold agglutinin disease (CAD) who have completed the 
CARDINAL study (BIVV009-03/EFC16215, Part B) or 
CADENZA study (BIVV009-04/EFC16216, Part B) in Japan. 
Protocol number: 
LTS17352 
Amendment number: 
Not applicable 
Compound number 
(INN/Trademark): 
BIVV009  
(sutimlimab) 
Brief title: 
Sutimlimab for the adult participants with cold agglutinin 
disease (CAD) who have completed Phase 3 studies 
(CARDINAL or CADENZA) in Japan.  
Study phase: 
Phase 3 
Sponsor name: 
Sanofi K.K. 
Legal registered 
address: 
3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
Monitoring team’s 
representative name 
and contact 
information 
Regulatory agency identifier number(s): 
IND: 
Not applicable 
EudraCT: 
Not applicable 
NCT: 
Not applicable 
WHO: 
U1111-1266-5421 
EUDAMED: 
Not applicable  
Other: 
Not applicable 
Date: 
30-Jun-2021
Total number of pages: 
48 
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Clinical Trial Protocol 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES  
DOCUMENT HISTORY 
 
Document 
Country/countries 
impacted by 
amendment 
Date, version 
Original Protocol 
 
30 June 2021, version 1 (electronic 1.0) 
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TABLE OF CONTENTS 
CLINICAL TRIAL PROTOCOL ....................................................................................................................... 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 ........................................................................................................................................ 10 
1.3 
SCHEDULE OF ACTIVITIES (SOA) .............................................................................................. 11 
2 
INTRODUCTION ............................................................................................................................ 13 
2.1 
STUDY RATIONALE...................................................................................................................... 13 
2.2 
BACKGROUND ............................................................................................................................. 13 
2.3 
BENEFIT/RISK ASSESSMENT ..................................................................................................... 14 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................. 15 
3.1 
APPROPRIATENESS OF MEASUREMENTS .............................................................................. 15 
4 
STUDY DESIGN ............................................................................................................................ 16 
4.1 
OVERALL DESIGN ........................................................................................................................ 16 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN ......................................................................... 16 
4.3 
JUSTIFICATION FOR DOSE ........................................................................................................ 16 
4.4 
END OF STUDY DEFINITION ....................................................................................................... 17 
5 
STUDY POPULATION .................................................................................................................. 18 
5.1 
INCLUSION CRITERIA .................................................................................................................. 18 
5.2 
EXCLUSION CRITERIA ................................................................................................................ 19 
5.3 
LIFESTYLE CONSIDERATIONS ................................................................................................... 20 
5.4 
SCREEN FAILURES...................................................................................................................... 20 
5.5 
CRITERIA FOR TEMPORARILY DELAYING ............................................................................... 20 
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6 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ................................................... 21 
6.1 
STUDY INTERVENTION(S) ADMINISTERED .............................................................................. 21 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY....................................................... 21 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING ....................................... 22 
6.4 
STUDY INTERVENTION COMPLIANCE ...................................................................................... 22 
6.5 
DOSE MODIFICATION .................................................................................................................. 22 
6.6 
CONTINUED ACCESS TO INTERVENTION AFTER THE END OF THE STUDY....................... 22 
6.7 
TREATMENT OF OVERDOSE ...................................................................................................... 22 
6.8 
CONCOMITANT THERAPY .......................................................................................................... 23 
7 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................................... 24 
7.1 
DISCONTINUATION OF STUDY INTERVENTION ...................................................................... 24 
7.1.1 
Permanent discontinuation ............................................................................................................ 24 
7.1.2 
Temporary discontinuation ............................................................................................................. 24 
7.1.3 
Rechallenge ................................................................................................................................... 24 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY .................................. 25 
7.3 
LOST TO FOLLOW UP ................................................................................................................. 26 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................................... 27 
8.1 
EFFICACY ASSESSMENTS ......................................................................................................... 27 
8.2 
SAFETY ASSESSMENTS ............................................................................................................. 27 
8.2.1 
Physical examinations ................................................................................................................... 27 
8.2.2 
Vital signs ....................................................................................................................................... 27 
8.2.3 
Electrocardiograms ........................................................................................................................ 28 
8.2.4 
Clinical safety laboratory assessments .......................................................................................... 28 
8.2.5 
Pregnancy testing .......................................................................................................................... 28 
8.3 
ADVERSE EVENTS (AES), SERIOUS ADVERSE EVENTS (SAES) AND OTHER 
SAFETY REPORTING ................................................................................................................... 28 
8.3.1 
Time period and frequency for collecting AE and SAE information ............................................... 28 
8.3.2 
Method of detecting AEs and SAEs ............................................................................................... 29 
8.3.3 
Follow-up of AEs and SAEs ........................................................................................................... 29 
8.3.4 
Regulatory reporting requirements for SAEs ................................................................................. 29 
8.3.5 
Pregnancy ...................................................................................................................................... 30 
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8.3.6 
Adverse event of special interest ................................................................................................... 30 
8.3.7 
Guidelines for reporting product complaints .................................................................................. 31 
8.4 
PHARMACOKINETICS .................................................................................................................. 31 
8.5 
GENETICS AND/OR PHARMACOGENOMICS ............................................................................ 31 
8.6 
BIOMARKERS ............................................................................................................................... 31 
8.7 
IMMUNOGENICITY ASSESSMENTS ........................................................................................... 31 
9 
STATISTICAL CONSIDERATIONS .............................................................................................. 32 
9.1 
SAMPLE SIZE DETERMINATION ................................................................................................. 32 
9.2 
POPULATIONS FOR ANALYSES ................................................................................................. 32 
9.3 
STATISTICAL ANALYSES ............................................................................................................ 32 
9.3.1 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ............................................................. 32 
9.3.2 
CONCOMITANT MEDICATIONS .................................................................................................. 32 
9.3.3 
Primary endpoint (Analysis of safety data) .................................................................................... 32 
9.3.3.1 
Adverse events .............................................................................................................................. 33 
9.4 
INTERIM ANALYSES .................................................................................................................... 33 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ........................ 34 
10.1 
APPENDIX 1: REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ....... 34 
10.1.1 
Regulatory and ethical considerations ........................................................................................... 34 
10.1.2 
Financial disclosure........................................................................................................................ 35 
10.1.3 
Informed consent process .............................................................................................................. 35 
10.1.4 
Data protection ............................................................................................................................... 36 
10.1.5 
Dissemination of clinical study data ............................................................................................... 38 
10.1.6 
Data quality assurance .................................................................................................................. 38 
10.1.7 
Source documents ......................................................................................................................... 39 
10.1.8 
Study closure ................................................................................................................................. 39 
10.1.9 
Publication policy ........................................................................................................................... 40 
10.2 
APPENDIX 2: CLINICAL LABORATORY TESTS ......................................................................... 40 
10.3 
APPENDIX 3: AES AND SAES: DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING ......................................................................... 41 
10.3.1 
Definition of AE .............................................................................................................................. 41 
10.3.2 
Definition of SAE ............................................................................................................................ 42 
10.3.3 
Recording and follow-up of AE and/or SAE ................................................................................... 44 
10.3.4 
Reporting of SAEs.......................................................................................................................... 45 
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10.4 
APPENDIX 8: COUNTRY-SPECIFIC REQUIREMENTS .............................................................. 46 
10.5 
APPENDIX 9: CONTINGENCY MEASURES FOR A REGIONAL OR NATIONAL 
EMERGENCY THAT IS DECLARED BY A GOVERNMENTAL AGENCY ................................... 46 
10.6 
APPENDIX 11: ABBREVIATIONS AND DEFINITIONS ................................................................ 46 
10.7 
APPENDIX 12: PROTOCOL AMENDMENT HISTORY ................................................................ 47 
11 
REFERENCES ............................................................................................................................... 48 
 
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LIST OF TABLES  
Table 1 - Objectives and endpoints ............................................................................................................... 15 
Table 2 - Overview of study interventions administered ............................................................................... 21 
Table 3 - Populations for analyses ................................................................................................................ 32 
 
LIST OF FIGURES  
Not applicable. 
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1 
PROTOCOL SUMMARY  
1.1 
SYNOPSIS  
Protocol title: 
An open-label study for sutimlimab in participants with cold agglutinin disease (CAD) who have 
completed the CARDINAL study (BIVV009-03/EFC16215, Part B) or CADENZA study 
(BIVV009-04/EFC16216, Part B) in Japan. 
Brief title: 
Sutimlimab for the adult participants with cold agglutinin disease (CAD) who 
have completed Phase 3 studies (CARDINAL or CADENZA) in Japan.  
Rationale: 
Currently, no approved treatment is available for CAD. Clinical studies have been performed to 
demonstrate the efficacy and safety of sutimlimab. This study intends to fulfil an unmet need 
while Sanofi is seeking regulatory approval of sutimlimab by providing treatment for the 
participants in Japan with CAD who have completed CARDINAL or CADENZA studies. 
Objectives and endpoints 
 
Objectives 
Endpoints 
Primary 
• 
Evaluation of overall safety profile for sutimlimab  
• 
Adverse event (AE) / serious adverse event (SAE) / 
adverse event of special interest (AESI) 
Secondary 
• 
Not applicable 
• 
Not applicable 
 
Overall design: 
Multi-center, single treatment-group study in Japan has an open label, repeated dose design. 
Brief summary:  
This is a multi-center, single treatment-group, open-label study to provide sutimlimab to the adult 
participants with CAD who have completed the CARDINAL or CADENZA studies, and 
benefitted from sutimlimab treatment in Japan. 
• Study and treatment duration: the period between the participant’s completion of the 
CARDINAL and CADENZA studies and sutimlimab or other appropriate CAD therapy 
still becoming commercially available to participants in Japan. 
 
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Number of participants: 
Maximum 7 participants will be enrolled.  
Intervention and duration: 
Intervention: sutimlimab 
Duration: The period between screening/baseline visit (upon the participant’s completion* of the 
CARDINAL and CADENZA studies) and end of treatment with sutimlimab in this study. 
Determined by sutimlimab or other appropriate CAD therapy becoming commercially available to 
participants in Japan. 
* “Completion” which means that participants completed the "End of Study" visit in Cardinal or 
Cadenza. Participants must complete the 9-week safety follow-up period as per protocol and then 
complete an "End of Study" visit.  
 
Study intervention 
Investigational medicinal product 
• Formulation: sutimlimab will be supplied to the pharmacy in 25 mL glass vials containing 
22 ml of 50 mg/mL sutimlimab with 10 mM sodium phosphate buffer, 140 mM NaCL, 
0.02% polysorbate 80 (Tween80), and water for injection. 
• Route of administration: Intravenous (IV) infusion 
• Dose regimen: sutimlimab dose is 6.5 g for participants whose weight is ≥39 kg to <75 kg 
or 7.5 g for participants ≥75 kg. The dosing schedule consists of an initial dose (Day 0), 
followed by a dose one week later (Day 7), which is followed by a maintenance dose 
every other week beginning on Day 21. 
Statistical considerations: 
• Primary endpoint: Evaluation of safety profile for sutimlimab 
- 
Summarize all adverse event (AE), serious adverse event (SAE) and adverse event of 
special interest (AESI).  
• Main secondary endpoints:  
- 
Not applicable. 
Data Monitoring/Other committee:  
Not applicable. 
 
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1.2 
SCHEMA  
Not applicable. 
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1.3 
SCHEDULE OF ACTIVITIES (SOA)  
Study visit 
Screening/ 
Baseline 
Treatment period 
Safety Follow-up 
Day 0 
Day 7 
Day 21 
Every 2 weeks 
after Day 21 
Every 3 months  
after Day 21 
9 weeks after 
Last Doseh 
Visit windows 
 
 
 2 days 
 2 days 
 14 days 
 2 days 
Written informed consent 
X 
 
 
 
 
 
Demographic & baseline characteristicsa 
X 
 
 
 
 
 
Detailed medical historyb c 
X 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
Pregnancy test (if applicable)d  
X 
 
X 
X 
Every 4 weeks after Day 21 
X 
Body weight and height 
X 
 
 
 
X 
Only weight 
X 
Only weight 
Physical examination, full 
X 
 
 
 
 
X 
Physical examination, brief 
 
 
 
 
X  
 
Vital signs (BP, PR, RR, oral temperature) 
X 
 
 
 
X  
X 
Hematology (local laboratory) 
X 
 
 
 
X 
X 
Clinical chemistry and urinalysis (local 
laboratory) 
X 
 
 
 
X 
X 
 Auto immune disorder (including SLE) sign and 
symptome  
X 
 
 
 
X 
X 
Study drug administrationf 
X 
X 
X 
X 
 
 
Prior & concomitant medications including 
transfusions 
X 
X 
X 
X 
X 
X 
Adverse eventsg 
X 
X 
X 
X 
X 
X 
 Abbreviation: BP = blood pressure, PR = pulse rate, RR = respiratory rate, SLE = systemic lupus erythematosus 
a Age, Sex, Race, Height (cm), Weight (kg), BMI (kg/ m2), presence or absence of CAD circulatory symptoms (Acrocyanosis or Raynaud's phenomenon, disabling circulatory symptoms), Hemoglobin, Total bilirubin 
and LDH (can be assayed by local lab. testing procedures) 
b Ongoing and relevant AEs from CARDINAL study and CADENZA study should be recorded in medical history. 
c New AEs that started between end of CARDINAL/CADENZA and start of this study should be recorded in medical history. 
d Female of child-bearing potential only. Serum pregnancy test to be performed at Screening. Urine pregnancy test to be performed prior to study drug infusion on Day 0 and at Safety follow-up Visit. Repeat urine 
pregnancy test every 4 weeks during treatment period. 
e Monitored for signs and symptoms of Auto immune disorder (including SLE) and evaluated appropriately. 
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f 
Sutimlimab doses of 6.5 g (if ≥39 kg to <75 kg) or 7.5 g (if ≥75 kg) based on participant’s baseline body weight will be administered via IV infusion over ~60±5 minutes on Days 0, 7, and every other week 
thereafter during treatment period. Participants with underlying cardiopulmonary disease may receive a 2-hour infusion with Sponsor approval. If a participant misses a scheduled dose (outside of the 2-day window 
or >17 days since last dose), they must return to site (unscheduled visit) to receive another loading dose and then resume bi-weekly dosing schedule one week later. 
g Adverse events will be recorded from the time the participant provides signed informed consent through the safety follow-up period. 
h If participants switch to marketed drug, safety follow-up should be continued until the day of infusion of marketed drug or for 9 weeks, whichever comes first. In some cases, if the transition to marketed drug may 
occur without interruption in the every other week infusion schedule, this time period could be approximately 2 weeks. 
 
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2 
INTRODUCTION  
CAD is a type of autoimmune hemolytic anemia caused by IgM-induced complement classical 
pathway (CP) activation. The disease is characterized by the presence of autoantibodies called 
cold agglutinins that typically bind to the I antigen uniformly present on the surface of all red 
blood cells (RBCs). The autoantibodies bind in accordance to their thermal amplitude and results 
in agglutination of RBCs, resulting in symptoms such as acrocyanosis and Raynaud syndrome. 
2.1 
STUDY RATIONALE  
Currently, no approved treatment is available for CAD. Clinical studies have been performed to 
demonstrate the efficacy and safety of sutimlimab. This study intends to fulfil an unmet need 
while Sanofi is seeking regulatory approval of sutimlimab by providing treatment for the 
participants with CAD who have completed CARDINAL and CADENZA studies and shown to 
benefit with sutimlimab treatment in Japan. 
CARDINAL study 
CARDINAL Part A was the pivotal 26-week, open-label, single-arm, Phase 3 study designed to 
evaluate the efficacy, safety, and tolerability of sutimlimab in participants with CAD with 
hemoglobin levels ≤10.0 g/dL and a recent history of blood transfusion (defined as at least 1 
transfusion during the last 6 months prior to enrollment). CARDINAL Part B is running for 2 
years following Last Participant Out (LPO) under Part A to provide supportive data on durability 
of response and long-term safety and tolerability. 
CADENZA study 
CADENZA Part A was the pivotal 26-week randomized, double-blind, placebo-controlled, Phase 
3 study designed to evaluate the efficacy and safety of sutimlimab in symptomatic participants 
with CAD who have hemoglobin levels ≤10.0 g/dL and who do not have a recent history of blood 
transfusion. CADENZA Part B is running for 1 year following LPO under Part A to provides 
supportive data on durability of response and long-term safety and tolerability. 
It is anticipated that participants could enter this study (LTS17352) immediately upon completion 
of the End of Study visit of CARDINAL and CADENZA studies Part B. 
2.2 
BACKGROUND  
Sutimlimab is an investigational humanized monoclonal IgG 4 serotype antibody (mAb) directed 
against human complement factor complement component 1 s subcomponent factor (C1s), a key 
subcomponent complex that along with complement component 1 r subcomponent (C1r) and 
complement component 1 q subcomponent (C1q) sits at the apex of the CP. By inhibiting C1s, 
BIVV009 prevents activation of the CP, thereby hypothesized to stop the mechanism by which 
hemolysis occurs in CAD. 
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A review of clinical experience with sutimlimab is in the Investigator’s Brochure (IB). 
2.3 
BENEFIT/RISK ASSESSMENT  
Considering the measures taken to minimize risk to the participant entering this study, the 
potential risks associated with treatment with sutimlimab are justified by the anticipated benefits 
that may be afforded to this participant. Therefore, only participants who demonstrated benefit 
and without major safety concern during treatment in Cardinal/Cadenza will be considered for 
participation.  
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of sutimlimab may be found in the IB and informed consent form (ICF). 
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3 
OBJECTIVES AND ENDPOINTS  
Table 1 - Objectives and endpoints  
Objectives 
Endpoints 
Primary 
• 
Evaluation of overall safety profile for sutimlimab 
• 
Adverse event (AE) /serious adverse event (SAE) / 
Adverse event of special interest (AESI) 
Secondary 
• 
Not applicable 
• 
Not applicable 
3.1 
APPROPRIATENESS OF MEASUREMENTS  
Clinical studies have been performed to demonstrate the efficacy and safety of sutimlimab. This 
study intends to fulfil an unmet critical need while Sanofi is seeking regulatory approval of 
sutimlimab by providing treatment for the participants with CAD who have completed 
CARDINAL and CADENZA studies in Japan and demonstrated benefit from treatment with 
sutimlimab. 
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4 
STUDY DESIGN  
4.1 
OVERALL DESIGN  
This Japanese single treatment-group, multi-center study has an open label, repeated dose design. 
This study is intended to be in place until sutimlimab becomes commercially available in Japan, 
but Sanofi reserves the right to end this study at any time.  
The participants can withdraw from this study at any time for any reason. Participants who were 
withdrawn from the study for whatever reason may not re-enter this study. 
The participants may continue to receive sutimlimab until the earliest of: the participant’s own 
voluntary withdrawal; this study ending; commercial treatment with sutimlimab becoming 
available to participants in Japan, or other appropriate therapy for CAD becomes available; or 
determination by the participant’s physician that this treatment is no longer appropriate, or 
meeting any of the early termination criteria defined in Section 7.2.  
The Sponsor reserves the right to end the study at any time. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN  
Parts A of the CARDINAL and CADENZA studies have been performed to assess the efficacy 
and safety of sutimlimab, Parts B of the CARDINAL and CADENZA studies are ongoing. This 
study is open-label extension study following completion of CARDINAL or CADENZA.  
The objective of this study is to provide access to sutimlimab for the participants and to 
characterize the safety of sutimlimab. Sponsor will only enroll Japanese participants with CAD 
who have completed CARDINAL and CADENZA studies and shown to benefit with sutimlimab 
treatment. Therefore, the Sponsor will focus evaluation on safety outcomes (AE/SAE/AESI). 
Efficacy, pharmacodynamic, pharmacokinetic, and patient reported outcome assessments are not 
required/included. 
4.3 
JUSTIFICATION FOR DOSE  
The same dose as used in CARDINAL and CADENZA studies was chosen. CARDINAL study 
has already confirmed safety and efficacy at below (1). 
6.5 g for participants whose weight at baseline is ≥39 kg to <75 kg or 7.5 g for participants ≥75 kg 
at baseline.  
The dosing schedule consists of an initial dose (Day 0), followed by a dose one week later (Day 
7), which is followed by a maintenance dose every other week beginning on Day 21. 
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Participants who miss a dose (ie, outside the dosing window or >17 days since last dose) should 
return to the study site for an unscheduled visit 1 as soon as possible in order to receive an 
additional loading dose and then resume bi-weekly dosing schedule 1 week after the loading dose. 
4.4 
END OF STUDY DEFINITION  
1. The study will continue until sutimlimab becomes commercially available to participants 
in Japan. 
2. Other appropriate therapy for CAD becomes available, whichever comes first; or 
3. The Sponsor ends the study. 
 
The Sponsor reserves the right to end the study at any time. 
The end of the study is defined as the date of the last visit in the study shown in the Schedule of 
Activities (SoA) for the last participant in the trial. 
A participant is considered to have completed the study if he/she has completed all phases of the 
study including the last visit. 
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5 
STUDY POPULATION  
When the participant enters this clinical study, participant information should be recorded on the 
case report form (CRF). 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
Up to 7 participants are expected to be enrolled in this program. 
5.1 
INCLUSION CRITERIA  
Participants are eligible to be included in this study only if all of the following criteria apply: 
Age 
I 01. Participant must be adults. 
Type of participant and disease characteristics 
I 02. Participants who have been enrolled in, and has completed Part B of CARDINAL or 
CADENZA study with demonstration of efficacy while on study considered by the 
investigator to be clinically meaningful 
I 03. Participants who are ongoing diagnosis of CAD (previously also referred to as primary 
CAD) 
I 04. Participants who continue to require treatment for CAD upon completion of participation 
in the previous study evidenced by return of CAD-related symptoms of anemia and/or 
deterioration on markers of hemolysis after the end of study visit following the 9-week 
safety follow up period. (9-week follow up period). 
I 05. Participants who have acceptable benefit/risk profile: 
a) No ongoing treatment emergent serious adverse events (TESAEs) related to 
sutimlimab. 
b) No events rendering benefit/risk unfavorable if sutimlimab is continued, based on the 
treating physician’s judgement. 
I 06. Participant who has acceptable infection risk, including:  
a) No active serious infection and/or active systemic encapsulated bacterial infection.  
Participants who have experienced a serious infection with encapsulated bacteria 
within the past 3 months are excluded.  
b) Received vaccination for Neisseria meningitidis and Streptococcus pneumoniae within 
the prior 5 years. 
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I 07. Participants who have no available appropriate alternative therapy for CAD and not 
eligible for any recruiting clinical trial with open-label treatment of CAD 
Weight 
I 08. Body weight of ≥39 kg at Screening/baseline. 
Sex, contraceptive/barrier method and pregnancy testing requirements 
I 09. If female and of childbearing potential or male and sexually active, participant who is 
willing to abstain from heterosexual intercourse in accordance with her or his preferred and 
usual life style, or to use 2 acceptable, effective contraceptive methods, while participating 
in this study and for 4 weeks after the last infusion of sutimlimab. 
Informed Consent 
I 10. Capable of giving signed informed consent as described in Appendix 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 this study if any of the following criteria apply: 
Medical conditions 
E 01. Clinical diagnosis of systemic lupus erythematosus (SLE); or immune complex mediated 
autoimmune disorders 
E 02. Participants who meet recent Rituximab and/or immunosuppressive therapy  
a) Has received Rituximab monotherapy or similar immunosuppressive monotherapy 
therapies within the prior 3 months.   
b) Has received Rituximab combination therapies (e.g., with bendamustine, fludarabine, 
ibrutinib, or cytotoxic drugs) within prior 6 months.    
E 03. Any of the following medical conditions: 
a) Active, serious intercurrent illness which will preclude enrolment until recovery is 
complete. 
b) Pregnancy or breast-feeding 
 
Other exclusions 
E 04. End of Study visit in CARDINAL or CADENZA took place more than 3 months before 
baseline visit in this study. 
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E 05. Individuals accommodated in an institution because of regulatory or legal order; prisoners 
or participants who are legally institutionalized  
E 06. Participant 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 07. Participants 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 ICH-GCP Ordinance E6) 
E 08. Any specific situation during study implementation/course that may raise ethics 
considerations 
E 09. Hypersensitivity reactions to sutimlimab or components thereof, or other allergy that, in 
the opinion of the Investigator, contraindicates participation in the study  
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 SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreened participants should be assigned a new participant number for every 
screening event. 
5.5 
CRITERIA FOR TEMPORARILY DELAYING   
Not applicable. 
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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 2 - Overview of study interventions administered  
Intervention label 
sutimlimab 
Intervention name 
sutimlimab 
Type  
Biologic 
Dose formulation 
Liquid 
Unit dose strength(s) 
6.5 g or 7.5 g  
Dosage level(s) 
6.5 g for participants whose weight is ≥39 kg to < 75 kg or 7.5 g for 
participants ≥75 kg. The dosing schedule consists of an initial dose 
(Day 0), followed by a dose one week later (Day 7), which is followed 
by a maintenance dose every other week beginning on Day 21. 
Route of administration 
IV infusion 
Use 
experimental 
IMP or NIMP 
IMP 
Packaging and labeling 
Study Intervention will be provided in a kit carton box. Each sutimlimab 
vial is labeled with a vial label and there will be two types of kits: 6-vial 
kit and 1-vial kit labeled with a carton booklet label. These will be 
labeled as per country requirement. 
Current/Former name(s) or alias(es) 
Not applicable 
Abbreviations: IMP = investigational medicinal product, IV = intravenous, NIMP = noninvestigational medicinal product  
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 and any discrepancies are 
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 supply or administer study intervention. All study intervention 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). 
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Any quality issue noticed with the receipt or use of sutimlimab (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 sutimlimab 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 sutimlimab and eliminate potential hazards. 
Under no circumstances will the Investigator supply sutimlimab to a third party (except for DTP 
shipment, for which a courier company has been approved by the Sponsor), allow the sutimlimab 
to be used other than as directed by this clinical trial protocol, or dispose of sutimlimab in any 
other manner.  
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING  
Not applicable. 
6.4 
STUDY INTERVENTION COMPLIANCE  
When participants are dosed at the study site, they will receive study intervention directly from 
the Investigator or designee, under medical supervision. The date and time of each dose (including 
start time, stop time, and time of interruption, in any) administered in the study site 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.  
6.5 
DOSE MODIFICATION  
Not applicable. 
6.6 
CONTINUED ACCESS TO INTERVENTION AFTER THE END OF THE STUDY  
Post-study access to study medication will not be provided.  
6.7 
TREATMENT OF OVERDOSE  
In the event of an overdose, the Investigator should: 
• Contact the Sponsor immediately. 
• Evaluate the participant to determine, in consultation with the Sponsor, whether study 
intervention should be interrupted or whether the dose should be reduced. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities  
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• Document appropriately in the CRF. 
• Report and submit as AESI. 
6.8 
CONCOMITANT THERAPY  
Participants will refrain from participation in any other investigational study drug trial in which 
receipt of any investigational drug occurred within 5 half-lives or 30 days, whichever is longer, 
prior to Day 0 and during the entire study.  
Any medication or vaccine (including over-the-counter or prescription medicines, recreational 
drugs, vitamins, and/or herbal supplements) or other specific categories of interest) 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 
The Sponsor should be contacted if there are any questions regarding concomitant or prior 
therapy. 
Treatment with rituximab monotherapy or rituximab combination therapies (eg, with 
bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) is prohibited. 
Topical therapies without risk of systemic absorption may be allowed, and non-prescription 
medications for treatment of minor intercurrent illnesses (headache, viral upper respiratory tract 
infections, etc.) are permitted at the discretion of the Investigator. Hormonal contraception in 
female participants are allowed provided participants are receiving stable treatment ≥3 months 
prior to Screening. Any medication taken by the participant during the study, along with its 
strength, frequency of dosing, and reason for its use, will be documented in the paripant’s source 
data and the CRF. 
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7 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL  
7.1 
DISCONTINUATION OF STUDY INTERVENTION  
Treatment may be discontinued temporarily or permanently. Any treatment discontinuation 
should be documented. 
7.1.1 Permanent discontinuation  
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention. If study intervention is permanently discontinued, the participant will be evaluated 
for safety. Such participants will not be eligible to re-enter the study. See the SoA for data to be 
collected at the time of discontinuation of study intervention and follow-up and for any further 
evaluations that need to be completed. 
Handling of participants after permanent intervention discontinuation 
Participants will be followed-up over the 9-week follow up period, or up to recovery or 
stabilization of any AE to be followed-up as specified in this protocol, whichever comes last. 
If possible, and after the permanent discontinuation of intervention, the participants will be 
assessed using the procedure normally planned for the last dosing day with the sutimlimab. 
All cases of permanent intervention discontinuation must be recorded by the Investigator in the 
appropriate pages of the CRF when considered as confirmed. 
7.1.2 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. For all temporary intervention discontinuations, duration should be 
recorded by the Investigator in the appropriate pages of the CRF.  
Temporary intervention discontinuation decided by the Investigator corresponds to more than 
1 dose not administered to the participant. 
In case of temporary discontinuation with dosing gap >17 days since last dose, participants must 
return to site (unscheduled visit) to receive another loading dose and then resume bi-weekly 
dosing schedule 1 week after the loading dose. 
7.1.3 Rechallenge  
Not applicable.  
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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, as shown in the SoA. See SoA for data to be collected at the time of 
study discontinuation and follow-up and for any further evaluations that need to be 
completed. 
• 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. 
• Not demonstration of efficacy while on study considered by the investigator to be 
clinically meaningful.  
• Occurrence of AEs that, in the opinion of the Investigator, may jeopardize participant 
safety or data integrity.  
• Occurrence of pregnancy in participant while receiving sutimlimab. 
• Intake of non-permitted concomitant medication or enrollment in another clinical study. 
• Diagnosis of SLE or immune complex mediated autoimmune disorders. 
• Once sutimlimab is available to participants commercially, or appropriate alternative 
therapy for CAD becomes available.  
 
If participants no longer wish to take the sutimlimab, they will be encouraged to complete the 9-
week post-treatment follow up period.    
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 
CRF 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. 
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Participants who have withdrawn from this study cannot be treated in this study again. Their 
inclusion and intervention 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 study site for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study. 
• Before a participant is deemed lost to follow up, the Investigator or designee must make 
every effort to regain contact with the participant (where possible, 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.  
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8 
STUDY ASSESSMENTS AND PROCEDURES  
• Study procedures and their timing are summarized in the SoA. 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 (eg, blood 
count, urine tests) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. 
8.1 
EFFICACY ASSESSMENTS  
Not applicable. 
8.2 
SAFETY ASSESSMENTS  
This section presents safety assessments other than AEs which are presented in Section 8.3.  
Planned time points for all safety assessments are provided in the SoA. 
8.2.1 Physical examinations  
• A complete physical examination will include, at a minimum, assessments of the general 
appearance, head and neck, eyes and ears, nose and throat, chest, lungs, heart, abdomen, 
extremities and joints, lymph nodes, skin, and neurology systems. Height and weight will 
also be measured and recorded. 
• A brief physical examination will include, at a minimum, assessments of the general 
appearance, chest, lungs, heart, abdomen, and skin. 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2 Vital signs  
Oral temperature, respiratory rate, supine blood pressure, and pulse rate will be assessed. Vital 
signs will be measured after the participant has been supine for at least 5 minutes. 
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8.2.3 Electrocardiograms  
Not applicable. 
8.2.4 Clinical safety laboratory assessments  
• See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and 
to the SoA (Section 1.3) for the timing and frequency.  
• Safety laboratory tests will be performed at a local laboratory. A serum pregnancy test is 
required if any urine pregnancy test is positive.  
• The clinical laboratory data consist of analysis results, including hematology, clinical 
chemistry, and urinalysis.  
• Only clinically significant laboratory test abnormalities will be recorded as AEs in the 
CRF. 
8.2.5 Pregnancy testing  
If the participant is a woman of childbearing potential, a urine pregnancy test will be performed 
every 4 weeks from Day 21, up to 24 hours before the sutimlimab infusion. A serum pregnancy 
test is required if any urine pregnancy test is positive. 
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. 
AE 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 OR AEs that are serious, considered related to the study intervention or study 
procedures, or that caused the participant to discontinue the study intervention (see Section 7).  
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 follow-up 
visit at the time points specified in the SoA (Section 1.3). 
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). 
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The Investigator will submit any updated SAE 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 AEs of 
special interest, 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). 
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, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and Investigators. 
• Serious adverse events that are considered expected will be specified in the reference 
safety information in the IB.  
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and Sponsor policy and 
forwarded to Investigators as necessary. 
• An Investigator who receives an Investigator safety report describing an SAE, 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. 
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8.3.5 Pregnancy  
• Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study intervention and until time period for 
reporting pregnancies should align with the time period for post-intervention. 
• 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 female 
participant or female partner of male participant (after obtaining the necessary signed 
informed consent from the female partner pregnancy).  
• While pregnancy as such is considered as an AESI, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE.  
• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. 
• The participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the Sponsor. 
• 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, he or she may learn of an SAE through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention or be withdrawn from the study. 
8.3.6 Adverse event of special interest   
An AESI is an AE (serious or nonserious) of scientific and medical concern specific to 
sutimlimab or this study, for which ongoing monitoring and immediate notification by the 
Investigator to Sanofi 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 of a female participant entered in a study as well as pregnancy occurring in a 
female partner of a male participant entered in a study with sutimlimab  
- 
Pregnancy occurring in a female participant entered in the clinical trial or in a female 
partner of a male participant entered in the clinical trial. 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, sutimlimab 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 sutimlimab 
- 
A symptomatic overdose (accidental or intentional) with the sutimlimab is an event 
suspected by the Investigator or spontaneously notified by the participant (not based on 
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systematic drug accountability/verification of consumption of solution for infusion) 
defined as intake of the study drug at dose significantly greater than scheduled, or 
administered in less than half the recommended duration of administration (i.e. 
<30 min), and resulting in clinical signs or symptoms attributable to the overdose. 
8.3.7 Guidelines for reporting product complaints  
Any defect in the sutimlimab 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  
Not applicable. 
8.5 
GENETICS AND/OR PHARMACOGENOMICS  
Not applicable. 
8.6 
BIOMARKERS  
Not applicable. 
8.7 
IMMUNOGENICITY ASSESSMENTS  
Not applicable. 
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9 
STATISTICAL CONSIDERATIONS  
The material in this section constitutes the statistical analysis plan for the study.  
9.1 
SAMPLE SIZE DETERMINATION  
Up to 7 participants will be enrolled to this study. 
Up to 7 participants are expected to complete CARDINAL study or CADENZA study, and to be 
enrolled to this study. 
9.2 
POPULATIONS FOR ANALYSES  
All the statistical analyses will be conducted on Safety population. Safety population is defined as 
all enrolled participants who take at least 1 dose of study intervention. 
Table 3 - Populations for analyses  
Population 
Description 
Safety 
All enrolled participants who take at least 1 dose of study intervention.  
9.3 
STATISTICAL ANALYSES  
The statistical analysis plan to be developed separately will include a more technical and detailed 
description of the statistical analyses described in this section. This section defines statistical 
analyses of the most important endpoints including primary endpoints only. 
9.3.1 DEMOGRAPHIC AND BASELINE CHARACTERISTICS  
Parameters identified in the schedule of activities (Section 1.3) will be summarized and listed. 
9.3.2 CONCOMITANT MEDICATIONS  
Medications will be coded according to the World Health Organization Drug Dictionary. All 
concomitant medications will be listed. 
9.3.3 Primary endpoint (Analysis of safety data)  
Summary tables of AEs defined in Section 9.3.3.1 will be provided. Each AE will be coded to a 
preferred term, high level group term, high level term, and system organ class, using the Medical 
Dictionary for Regulatory Activities (MedDRA). All AEs and safety parameters described in 
Section 1.3 and Section 8.2 will be listed (when corresponding CRF data are available). 
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9.3.3.1 Adverse events  
General common rules for adverse events 
The primary focus of adverse event reporting will be on treatment-emergent adverse events 
(TEAEs). Ongoing AE from CARDINAL study and CADENZA study will be recorded in 
medical history. New AE that started between end of CARDINAL/CADENZA and start of this 
study will be recorded in medical history. 
TEAEs are defined as AEs that developed, worsened or became serious during the treatment-
emergent period (from the time from the first dose of study treatment in this study to the last 
contact on study). 
Analysis of all adverse events 
Summary table will be provided for the following types of TEAEs: all TEAEs, all treatment 
emergent AESI (defined with a PT or a prespecified grouping), all treatment emergent SAEs and 
all TEAEs leading to permanent treatment discontinuation. 
The AE summaries will be generated with number (%) of participants experiencing at least one 
event.  
All deaths will be listed. 
9.4 
INTERIM ANALYSES  
Not applicable. 
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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 and the applicable amendments and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical Guidelines 
- 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
- 
Applicable laws and regulations (eg, data protection law as General Data Protection 
Regulation - GDPR) 
• The protocol, protocol amendments, ICF, IB 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 
- 
The finding reveals a substantial risk of a serious health condition or has 
reproductive importance, AND has analytical validity, AND has clinical validity.  
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- 
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 study site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, 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 or their legally authorized representative, and answer all questions regarding 
the study, including what happens to the participant when his/her participation ends (post-
trial access strategy for the study).  
• Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative 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 General Data Protection Regulation 
(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. 
• 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 
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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 or their legally authorized 
representative, where applicable.  
Participants who are rescreened are required to sign a new ICF. 
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 (General Data Protection Regulation). 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, IRB/IEC 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 expected to modify 
the drug response/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 
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 
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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, 
- 
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/). 
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Therefore, personal data will be securely shared by Sanofi with other phamaceutical 
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 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 participants 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”.  
10.1.6 Data quality assurance  
• All participant data relating to the study will be recorded on printed CRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The 
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Investigator is responsible for verifying that data entries are accurate and correct by 
physically signing the CRF.  
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
• 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.  
10.1.7 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 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.  
10.1.8 Study closure  
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the Sponsor. Study sites will be closed upon study completion. A 
study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.  
Reasons for 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:  
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• 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 
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. 
10.1.9 Publication policy  
• The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor 
before submission. This allows the Sponsor to protect proprietary information and to 
provide comments.  
• The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In 
this case, a coordinating Investigator will be designated by mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.  
10.2 
APPENDIX 2: CLINICAL LABORATORY TESTS  
The following determinations will be performed by the local laboratory. 
Hematology 
• Hematocrit 
• Hemoglobin 
• Red blood cell count 
• White blood cell count with differential 
• Platelet count 
Clinical chemistry 
• Sodium 
• Potassium 
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• Calcium 
• Magnesium 
• Chloride 
• Total protein 
• Albumin 
• Glucose 
• Creatinine 
• Blood urea nitrogen 
• Lactate dehydrogenase 
• Creatine kinase 
• ALT 
• AST 
• ALP 
• Gamma glutamyl transferase 
• Total and direct bilirubin 
Urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by 
dipstick 
• Microscopic examination (if blood or protein is abnormal) 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
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 participant 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. 
Events meeting the AE definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the 
Investigator (ie, not related to progression of underlying disease),   
- 
Symptomatic and/or  
- 
Requiring either corrective treatment or consultation, and/or  
- 
Leading to sutimlimab discontinuation 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.  
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: 
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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. 
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) 
Is a suspected transmission of any infectious agent via an authorized medicinal 
product 
g) 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:  
o Allergic bronchospasm   
o Blood dyscrasias (ie, agranulocytosis, aplastic anemia, bone marrow 
aplasia, myelodysplasia, pancytopenia, etc) 
o Convulsions (seizures, epilepsy, epileptic fit, absence, etc).  
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- 
Development of drug dependence or drug abuse  
- 
ALT >3 × ULN + total bilirubin >2 × ULN or asymptomatic ALT increase 
>10 × ULN  
- 
Suicide attempt or any event suggestive of suicidality  
- 
Syncope, loss of consciousness (except if documented as a consequence of 
blood sampling)  
- 
Bullous cutaneous eruptions   
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. 
• 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 
The Investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 1 of the following categories: 
• Mild: An event that is easily tolerated by the participant, causing minimal discomfort and 
not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort to interfere with normal everyday 
activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. “Severe” is a category used for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as described 
in the definition of an SAE, NOT when it is rated as severe. 
Assessment of causality 
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• 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. 
• 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 Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the Investigator has minimal 
information to include in the initial report to Sanofi. However, it is very important that 
the Investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to Sanofi. 
• 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 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 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.  
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• Contacts for SAE reporting will be provided. 
10.4 
APPENDIX 8: COUNTRY-SPECIFIC REQUIREMENTS  
Not applicable. 
10.5 
APPENDIX 9: CONTINGENCY MEASURES FOR A REGIONAL OR NATIONAL 
EMERGENCY THAT IS DECLARED BY A GOVERNMENTAL AGENCY  
Not applicable. 
10.6 
APPENDIX 11: ABBREVIATIONS AND DEFINITIONS  
Abbreviations 
Definitions 
AE 
adverse event 
AESI 
adverse event of special interest 
CAD 
cold agglutinin disease 
CIOMS 
Council for International Organizations of Medical Sciences 
CONSORT 
Consolidated Standards of Reporting Trials 
CP 
complement classical pathway 
CRF 
case report form 
C1q 
complement component 1 q subcomponent 
C1r 
complement component 1 r subcomponent 
C1s 
complement component 1 s subcomponent 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
IEC 
Independent Ethics Committees 
IR 
Investigator Registry 
IRB 
Institutional Review Boards 
IV 
intravenous 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
RBC 
red blood cell 
SAE 
serious adverse event 
SIP 
Shared Investigator Platform 
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Abbreviations 
Definitions 
SLE 
systemic lupus erythematosus 
SoA 
Schedule of Activities 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
 
 
10.7 
APPENDIX 12: PROTOCOL AMENDMENT HISTORY  
Not applicable. 
 
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Clinical Trial Protocol 
BIVV009-LTS17352 - sutimlimab 
30-Jun-2021 
Version number: 1 
 
Property of the Sanofi group - strictly confidential 
Page 48 
11 
REFERENCES  
1. Röth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, et al. Sutimlimab in 
Cold Agglutinin Disease. N Engl J Med. 2021 Apr 8;384(14):1323-1334. doi: 
10.1056/NEJMoa2027760. 
 
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SAP_001.pdf: 




Statistical Analysis Plan  
07-Oct-2022 
Product Code-Study Number - LTS17352-BIVV009 
Version number: 1.0 
Property of the Sanofi group - strictly confidential 
Page 3 
TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ................................................................................................................... 1 
SIGNATURE ................................................................................................................................................... 2 
TABLE OF CONTENTS .................................................................................................................................. 3 
VERSION HISTORY ....................................................................................................................................... 5 
1 
INTRODUCTION .............................................................................................................................. 6 
1.1 
STUDY DESIGN .............................................................................................................................. 6 
1.2 
INTERVENTION GROUP ................................................................................................................ 6 
1.3 
OBJECTIVE AND ENDPOINTS ...................................................................................................... 6 
2 
SAMPLE SIZE DETERMINATION .................................................................................................. 6 
3 
ANALYSIS POPULATIONS ............................................................................................................ 6 
4 
STATISTICAL ANALYSES ............................................................................................................. 7 
4.1 
GENERAL CONSIDERATIONS ...................................................................................................... 7 
4.2 
BASELINE AND DEMOGRAPHICS CHARACTERISTICS ............................................................. 7 
4.3 
PRIMARY ENDPOINT(S) ANALYSIS .............................................................................................. 7 
4.3.1 
General common rules for primary endpoint(s) analysis ................................................................. 7 
4.3.2 
Adverse event .................................................................................................................................. 8 
4.4 
OTHER ANALYSES......................................................................................................................... 9 
4.4.1 
Extent of exposure ........................................................................................................................... 9 
4.4.2 
Hemoglobin, bilirubin and lactate dehydrogenase ........................................................................... 9 
4.5 
INTERIM ANALYSES ...................................................................................................................... 9 
4.6 
LISTING
IF ANY
 ...................................................................................................................... 10 
5 
SUPPORTING DOCUMENTATION .............................................................................................. 11 
5.1 
APPENDIX 1: ABBREVIATIONS AND DEFINITIONS .................................................................. 11 
5.2 
APPENDIX 2: MEDDRA SYSTEM ORGAN CLASS LIST  INTERNATIONALLY AGREED 
ORDER .......................................................................................................................................... 12 
 
 
 
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Statistical Analysis Plan  
07-Oct-2022 
Product Code-Study Number - LTS17352-BIVV009 
Version number: 1.0 
Property of the Sanofi group - strictly confidential 
Page 4 
List of tables  
Table 1 - Major changes in statistical analysis plan ........................................................................................ 5 
Table 2 - Objectives and endpoints ................................................................................................................. 6 
Table 3- Populations for analyses ................................................................................................................... 6 
Table 4 - Sorting of AE tables ......................................................................................................................... 8 
Table 5 - Analyses of adverse events ............................................................................................................. 8 
Table 6 - Selections for AESIs ........................................................................................................................ 9 
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Statistical Analysis Plan  
07-Oct-2022 
LTS17352-BIVV009 - sutimlimab 
Version number: 1.0 
Property of the Sanofi group - strictly confidential 
Page 5 
VERSION HISTORY 
This Statistical Analysis Plan (SAP) for study LTS17352 is based on the protocol dated 30-Jun-
2021. This section summarizes major changes to the statistical analysis features in the SAP. The 
first participant was enrolled on 30-Oct-2021. 
Table 1 - Major changes in statistical analysis plan 
SAP 
Version
Approval 
Date 
Changes 
Rationale 
1.0 
07-Oct-2022 
Not Applicable 
Original version 
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Statistical Analysis Plan  
07-Oct-2022 
LTS17352-BIVV009 - sutimlimab 
Version number: 1.0 
Property of the Sanofi group - strictly confidential 
Page 6 
1 
INTRODUCTION 
1.1 
STUDY DESIGN 
This is a multi-center, single treatment-group, open-label study with repeated dose design. 
1.2 
INTERVENTION GROUP 
Sutimlimab dose is 6.5 
 kg to <75 kg or 7.5 g for 
 kg at baseline. 
1.3 
OBJECTIVE AND ENDPOINTS 
Table 2 - Objectives and endpoints 
Objectives 
Endpoints 
Primary 
 
Evaluation of overall safety profile for sutimlimab 
 
Adverse event (AE) /serious adverse event (SAE) / 
Adverse event of special interest (AESI) 
Secondary 
 
Not applicable 
 
Not applicable 
2 
SAMPLE SIZE DETERMINATION 
Up to 7 participants will be enrolled to this study. 
Up to 7 participants are expected to complete CARDINAL study or CADENZA study, and to be 
enrolled to this study. 
3 
ANALYSIS POPULATIONS 
The following population for analyses is defined:  
Table 3- Populations for analyses 
Population 
Description 
Safety 
All enrolled participants who take at least 1 dose of study intervention.  
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Statistical Analysis Plan  
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4 
STATISTICAL ANALYSES 
4.1 
GENERAL CONSIDERATIONS 
Continuous data will be summarized using the number of observations available, mean, standard 
deviation (SD), median, minimum, and maximum. Categorical and ordinal data will be 
summarized using the count and percentage of participants. 
Baseline is defined as the day of the first dose (Day 0). 
Unless otherwise specified, analyses will be performed by intervention group and overall for 
baseline and demographics characteristics. 
Among the descriptive statistics, the mean, standard deviation, and median should be rounded to 
one more digit than the number of digits in the measurement data, and the minimum and maximum 
values should have the same number of digits as in the measurement data. Percentages should be 
expressed to the first decimal place. 
4.2 
BASELINE AND DEMOGRAPHICS CHARACTERISTICS 
Descriptive statistics will be calculated for age (year), height (cm), weight (kg), BMI (kg/m^2) and 
Presence of CAD circulatory symptoms at baseline by intervention group and overall. 
4.3 
PRIMARY ENDPOINT(S) ANALYSIS 
4.3.1 General common rules for primary endpoint(s) analysis 
The primary analyses will be performed on the safety population as defined in Section 3. 
TEAEs are defined as AEs that developed, worsened or became serious during the treatment-
emergent period. 
The primary focus of AE reporting will be on TEAEs.   
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 post-treatment AE.  
Multiple occurrences of the same event in the same participant will be counted only once in the 
tables. 
The AE tables will be sorted as indicated in Table 4.  
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Table 4 - Sorting of AE tables 
AE presentation 
Sorting rules 
SOC and PT 
By the internationally agreed SOC a order and decreasing frequency of PTsb,c   
a Appendix2 for sort order of SOC 
b Sorting will be based on the overall incidence. 
c 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.   
4.3.2 Adverse event 
Analysis of all adverse events 
The overview of TEAE with the details below will be generated: 
 Total number of TEAEs 
 Number of subjects with at least one TEAE 
 Number of subjects with at least one related TEAE 
 Total number of treatment emergent AESIs  
 Number of subjects with at least one treatment emergent AESI 
 Number of subjects with at least one related treatment emergent AESI 
 Total number of treatment emergent SAEs 
 Number of subjects with at least one treatment emergent SAE 
 Number of subjects with at least one related treatment emergent SAE 
 Number of subjects who discontinued treatment and/or the study due to a TEAE  
 Number of deaths  
The AE summaries of Table 5 will be generated with number (%) of participants experiencing at 
least one event (if these types of AE are observed).    
Table 5 - Analyses of adverse events 
Type of AE 
MedDRA levels 
TEAEs 
Primary SOC and PT 
Treatment emergent AESIs 
Primary SOC and PT 
Treatment emergent SAEs  
Primary SOC and PT 
TEAEs leading to permanent treatment discontinuation 
Primary SOC and PT 
Deaths 
Primary SOC and PT 
Analysis of adverse events of special interest (AESIs) 
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Adverse events of special interest (AESIs) will be selected for analyses as indicated in Table 6. 
Number (%) of participants experiencing at least one event will be provided for each event of 
interest. Tables will be sorted as indicated in Table 4. 
Table 6 - Selections for AESIs 
AESIs  
Symptomatic overdose with study drug 
Pregnancy 
4.4 
OTHER ANALYSES 
4.4.1 Extent of exposure 
Study drug exposure, measured by the duration of study treatment and total actual BIVV009 dose, 
will be summarized for the Safety population. For these items, the mean, standard deviation, and 
median will be displayed to the second decimal place, and the minimum and maximum values 
will be displayed to the first decimal place. 
The duration of the study treatment (in weeks) is defined as (date of last dose  date of first dose + 
15)/7.  
The actual dose administered at each infusion is calculated as (Total volume administered / Total 
volume prepared) * assigned dose.  
The total BIVV009 dose is the summation of all actual dose administered. 
Study drug compliance will also be summarized for Safety population. 
Study drug compliance for a subject is measured by the percent of number of doses received out 
of the number of protocol specified doses. For example, for a subject who completes the study 
treatment at Day259, the number of protocol specified doses is 20. The compliance of the subject 
will be the number of doses received divided by 20 expressed in percentage. For a subject who 
discontinues early, the number of protocol specified doses is the number of scheduled doses prior 
to the date of discontinuation. 
4.4.2 Hemoglobin, bilirubin and lactate dehydrogenase 
Hemoglobin (g/dL), bilirubin (mg/dL) and lactate dehydrogenase (U/L) at baseline and at the last 
measurement will be summarized for Safety population and for the participants who completed 
the study. 
4.5 
INTERIM ANALYSES 
Not applicable. 
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4.6 
LISTING
IF ANY
  
1. Informed Consent 
2. Eligibility (if any violation(s)) 
3. Demography (including Height and Weight) 
4. Presence of CAD circulatory symptoms 
5. Clinical Laboratory Test 
6. Medical History 
7. Infusion of Study Drug 
8. Date of Visit 
9. Completion/Discontinuation 
10. Adverse Event 
11. Adverse Event of special interest (Pregnancy) 
12. Adverse Event of special interest (Overdose) 
13. Prior and/or Concomitant Medication(s) 
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5 
SUPPORTING DOCUMENTATION 
5.1 
APPENDIX 1: ABBREVIATIONS AND DEFINITIONS  
Abbreviations 
Definitions 
AE 
adverse event 
AESI 
adverse event of special interest 
CAD 
cold agglutinin disease 
-mab 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
SAE 
serious adverse event 
TEAE 
treatment-emergent adverse event 
 
 
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Statistical Analysis Plan  
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LTS17352-BIVV009 - sutimlimab 
Version number: 1.0 
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5.2 
APPENDIX 2: MEDDRA SYSTEM ORGAN CLASS LIST  INTERNATIONALLY 
AGREED ORDER 
Reference: MedDRA 23.1 - September 2020 
1. Infections and infestations 
2. Neoplasms benign and malignant (including cysts and polyps) 
3. Blood and the lymphatic system disorders 
4. Immune system disorders 
5. Endocrine disorders 
6. Metabolism and nutrition disorders 
7. Psychiatric disorders 
8. Nervous system disorders 
9. Eye disorders 
10. Ear and labyrinth disorders 
11. Cardiac disorders 
12. Vascular disorders 
13. Respiratory, thoracic and mediastinal disorders 
14. Gastrointestinal disorders 
15. Hepato-biliary disorders 
16. Skin and subcutaneous tissue disorders 
17. Musculoskeletal, connective tissue and bone disorders 
18. Renal and urinary disorders 
19. Pregnancy, puerperium and perinatal conditions 
20. Reproductive system and breast disorders 
21. Congenital and familial/genetic disorders 
22. General disorders and administration site conditions 
23. Investigations 
24. Injury, poisoning and procedural complications 
25. Surgical and medical procedures 
26. Social circumstances 
27. Product issue. 
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