Safety and Tolerability Study in Adults With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088

Study Overview
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Brief Summary
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Primary Objective: To assess the long-term safety and tolerability in patients with cold agglutinin disease (CAD), after multiple doses of SAR445088 Secondary Objective: To assess, in patients with cold agglutinin disease (CAD), after multiple doses of SAR445088: The long-term effect of SAR445088 on complement mediated hemolysis The long-term pharmacodynamics (PD) effect of SAR445088 relating to complement inhibition The long-term pharmacokinetic (PK) profile of SAR445088 The long-term immunogenicity of SAR445088

Detailed Description
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The screening period for this study is up to 6 weeks. The treatment period for this study will continue for 2 years after last participant entered Part 2 (either having switched from Part 1 or as a SAR445088-naïve participant), or until SAR445088 development is discontinued, whichever comes first.

Official Title
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An Open-label, Long-term, Safety and Tolerability Study of SAR445088 in Participants With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088

Conditions
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Autoimmune Haemolytic Anaemia

Intervention / Treatment
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* Drug: SAR445088


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adult patients ≥18 years of age with CAD who were previously treated with SAR445088 and met criteria the below criteria for entry into Part 1: met the eligibility criteria of a previous study evaluating SAR445088; successfully enrolled and completed dosing in a previous study evaluating SAR445088; successfully completed end of study procedures in a previous study evaluating SAR445088; and per Investigator judgement, had a favorable benefit-to-risk profile after receiving SAR445088. OR were never treated with SAR445088 before entering Part 2, and met the below criteria to establish CAD diagnosis: chronic hemolysis; polyspecific direct antiglobulin test (DAT) positive status; monospecific DAT strongly positive for C3d; cold agglutinin [CAg] titer ≥64 at 4°C; IgG DAT ≤1+; hemoglobin level ≤10 g/dL; elevated bilirubin not attributable to liver disease; Documented vaccinations against encapsulated bacterial pathogens given within five years of enrollment and at least 14 days prior to dosing (vaccinations have to be initiated at least 14 days prior to dosing and completed before Week 5 of Part 2). Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants. Having given written informed consent prior to undertaking any study-related procedure. Exclusion Criteria: Cold agglutinin syndrome secondary to infection, rheumatologic disease, or known high-grade hematologic malignancy, or known solid organ tumor. Clinically relevant infection within 1 month of enrollment. Clinical diagnosis of systemic lupus erythematosus (SLE). Treatment with anti-CD20 monotherapy within 3 months or anti-CD20 combination therapies within 6 months prior to screening. Concurrent treatment with systemic immunosuppressive agents targeting B- or T-cell function and/or cytotoxic agents within 3 months prior to screening. Concurrent treatment with other systemic immunosuppressants within 5.5 half-lives of the drug prior to screening. Any specific complement system inhibitor other than SAR445088 (eg, eculizumab) within 3 months prior to screening. Concurrent treatment with systemic corticosteroids other than a stable daily dose equivalent to ≤10 mg/day prednisone within 3 months prior to screening. History of hypersensitivity to SAR445088 or any of its components. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR445088<br>Repeat dose of SAR445088 | Drug: SAR445088<br>* Pharmaceutical form: solution for injection Route of administration: IV and SC (Part 1) IV (Part 2)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAE) | The number of participants experiencing TEAEs will be reported for the overall safety population. | Day 1 or Day 1-IV to end of study, approximately 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in total bilirubin over time | Assessment of total bilirubin | Day 1 or Day 1-IV to end of study, approximately 6 years | 
| Mean change from baseline in hemoglobin over time | Assessment of hemoglobin | Day 1 or Day 1-IV to end of study, approximately 6 years | 
| Mean change from baseline in lactate dehydrogenase over time | Assessment of lactate dehydrogenase | Day 1 or Day 1-IV to end of study, approximately 6 years | 
| Mean change from baseline in reticulocyte count over time | Assessment of reticulocyte count | Day 1 or Day 1-IV to end of study, approximately 6 years | 
| Complement System Classical Pathway Levels as Measured by WIESLAB Assay | Inhibition by SAR445088 of the complement system classical pathway measured by the WIESLAB assay. | Day 1 or Day 1-IV to Week 48-IV | 
| Complement System Alternative Pathway Levels as Measured by WIESLAB Assay | Part 1: Effect of SAR445088 on the complement system alternative pathway measured by the WIESLAB assay. | Day 1 to Week 24 | 
| Mean change in CH50 over time | Complement CH50 is a blood test that helps us determine whether protein abnormalities and deficiencies in the complement system are responsible for any increase in autoimmune activity. It will be assessed using complement assays. | Day 1 or Day 1-IV to end of study, approximately 6 years | 
| Total Complement Factor C4 Levels | Total C4 Levels will be assessed in plasma using complement assays | Day 1 or Day 1-IV to end of study, approximately 6 years | 
| PK parameter: Cmax | Maximum observed concentration (Cmax) of SAR445088 in plasma will be assessed | Day 1 or Day 1-IV to Week 48-IV | 
| PK Parameter: AUC | Area under the plasma concentration versus time curve calculated using the trapezoidal method at steady state | Day 1 or Day 1-IV to Week 48-IV | 
| Number of participants with anti-SAR445088 antibodies | The immunogenicity for SAR445088 will be assessed by summarizing the number of participants with anti-SAR445088 antibodies (ADA) | Day 1 or Day 1-IV to end of study, approximately 6 years |