Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA)

A Multicenter, Open-label, Non-randomized, Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia

Primary Objectives:

• Part A: To evaluate the safety and tolerability of subcutaneous injections of isatuximab in adults with wAIHA
• Part B: To evaluate the efficacy of the selected dose in adults with wAIHA

Secondary Objectives:

• Part A (Cohorts 2 and 3 only)
• To evaluate the efficacy of isatuximab in adults with wAIHA
• To evaluate the durability of response to isatuximab and time to response
• To evaluate the impact of isatuximab treatment on fatigue

Part B

• To evaluate the safety and tolerability of isatuximab in adults with wAIHA
• To evaluate the durability of response to isatuximab and time to response
• To evaluate the impact of isatuximab treatment on fatigue

Parts A (all Cohorts) and B

• To evaluate the effect of isatuximab on markers of hemolysis
• To characterize the pharmacokinetic profile of isatuximab in adults with wAIHA
• To evaluate the immunogenicity of isatuximab

28 weeks (including screening)

Inclusion criteria :

• Participant must be ≥18 to years of age, inclusive, at the time of signing the informed consent.

  - Males and females with a confirmed diagnosis of primary w AIHA or systemic lupus erythematosus (SLE)-associated w AIHA (without other SLE-related manifestations apart from cutaneous and musculoskeletal manifestations) who meet the following criteria:

  1. Hemoglobin level <10 g/dL at screening.

  2. Hemolysis (haptoglobin ≤40 mg/dL and total or indirect/unconjugated bilirubin above the upper limit of normal).

  3. Positive direct antiglobulin test (DAT) (IgG or IgG + complement C3d pattern or IgM warm autoantibodies (positive dual DAT)).

     • Participants who have previously failed to maintain a sustained response after treatment with corticosteroids (corticosteroid-refractory or corticosteroid-dependent primary wAIHA).
     • Part A only: Participants who have previously failed to maintain a sustained response after treatment with rituximab (or other anti-CD20 monoclonal antibodies). The last dose of the anti-CD20 antibody must have been administered at least 12 weeks before enrollment.
     • Part B: Participants who have had an insufficient response to at least 1 prior therapy in addition to corticosteroids (splenectomy is regarded as a prior therapy).
     • Contraceptive use by men and women

     Exclusion criteria:

• Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his or her participation in the study as determined by the Investigator.

  • Serious infection that required hospitalization within 3 months prior to enrollment.
  • Secondary wAIHA from any cause including drugs, lymphoproliferative disorders, infectious or autoimmune disease (SLE without other SLE-related manifestations apart from cutaneous and musculoskeletal manifestations is allowed), or active hematologic malignancies. Participants with positive antinuclear antibodies but without a definitive diagnosis of an autoimmune disease are allowed.
  • History of coagulation or bleeding disorders (Evans Syndrome is allowed).
  • Uncontrolled or active HBV or HCV infection
  • HIV infection.
  • Serum gammaglobulin levels <3 g/L.
  • Females who are pregnant, lactating, or considered unreliable with respect to contraceptive practice.
  • Concurrent treatment with corticosteroids, unless the participant has been on a stable daily dose for ≥ 15 days prior to enrollment.
  • Treatment with cyclophosphamide within 4 weeks prior to enrollment.
  • Treatment with cytotoxic drugs (other than cyclophosphamide) within 12 weeks prior to enrollment.
  • Treatment with non-cytotoxic, immunomodulatory drugs (including but not limited to Cyclosporine, Sirolimus, Tacrolimus, Idelalisib, Ibrutinib), excluding biologic agents, within 4 weeks prior to enrollment.
  • Treatment with any biologic agent within 12 weeks prior to enrollment.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.