A Safety and Tolerability Study of BIVV020 in Adults With Cold Agglutinin Disease

Study Overview
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Brief Summary
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Primary Objective: To assess the safety and tolerability in participants with cold agglutinin disease (CAD), after a single dose of intravenous (IV) BIVV020 Secondary Objectives: To assess, in participants with cold agglutinin disease, after a single dose of intravenous (IV) BIVV020: The effect of BIVV020 on complement mediated hemolysis The pharmacodynamics (PD) of BIVV020 relating to complement inhibition The pharmacokinetics (PK) of BIVV020 The immunogenicity of BIVV020

Detailed Description
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Up to 23 weeks (screening period up to 8 weeks, treatment period 15 weeks)

Official Title
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A Multicenter, Phase 1b, Open Label, Nonrandomized, Single Dose Study Evaluating the Safety, Tolerability and Activity of BIVV020 in Adults With Cold Agglutinin Disease

Conditions
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Autoimmune Haemolytic Anaemia

Intervention / Treatment
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* Drug: BIVV020


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Male and/or female patients, ≥ 18 years of age with cold agglutinin disease as defined by: Chronic hemolysis per Investigator's judgement, Polyspecific direct antiglobulin test (DAT) positive, Monospecific DAT strongly positive for C3d, Cold agglutinin (CAg) titer ≥ 64 at 4 C; and, IgG DAT ≤1+. A hemoglobin level ≤11 mg/dL. A total bilirubin level above the normal reference range that is thought to be due to hemolysis. Documented vaccinations against encapsulated bacterial pathogens (Neisseria meningitidis, including serogroup B meningococcus and Streptococcus pneumoniae) within five years of screening or willing to complete protocol specified vaccinations. 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 of any kind within one month preceding screening. Treatment with anti-CD20 monotherapy within three months or anti CD20 combination therapies within six 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 within three months prior to screening. Concurrent treatment with systemic corticosteroids other than a stable daily dose equivalent to ≤10 mg/day prednisone within three months prior to screening. If female, pregnant or lactating. 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: BIVV020 IV<br>Single administration dose 1, plus two optional doses of BIVV020 administered intravenously. | Drug: BIVV020<br>* Pharmaceutical form:solution for injection Route of administration: intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events (AEs) | Number of participants with adverse events (AEs) | Screening to Day 106 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in bilirubin over time | Assessment of total bilirubin | Day 1 to Day 106 | 
| Mean change from baseline in hemoglobin over time | Assessment of hemoglobin | Day 1 to Day 106 | 
| Complement System Classical Pathway Levels as Measured by WIESLAB Assay | Inhibition by BIVV020 of the complement system classical pathway measured by the WIESLAB assay | Day 1 to Day 106 | 
| Complement System Alternative Pathway Levels as Measured by WIESLAB Assay | Effect of BIVV0020 on the complement system alternative pathway measured by the WIESLAB assay | Day 1 to Day 106 | 
| Total Complement (CH50) Levels | 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 to Day 106 | 
| Total Complement Factor C4 Levels | Total C4 Levels will be assessed in plasma using complement assays | Day 1 to Day 106 | 
| PK parameter: Cmax | Observed maximum plasma concentration | Day 1 to Day 106 | 
| PK parameter: tmax | Observed first time to reach Cmax | Day 1 to Day 106 | 
| PK parameter: AUClast | Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast | Day 1 to Day 106 | 
| PK parameter: AUC0-∞ | Calculated area under the plasma concentration versus time curve extrapolated to infinity | Day 1 to Day 106 | 
| Number of participants with anti-BIVV antibodies | Observed number of participants with BIVV020 antibodies | Day 1 to Day 106 |