Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA)
Investigational Medication for Warm Autoimmune Hemolytic Anemia (wAIHA)
Study Overview
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
Study Details
28 weeks (including screening)
Eligibility Criteria
You may be eligible for this study if you meet the following criteria:
- Conditions: Warm Autoimmune Hemolytic Anemia (wAIHA)
-
Age: 18 years or above
-
Gender: All
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:
- Hemoglobin level <10 g/dL at screening.
- Hemolysis (haptoglobin ≤40 mg/dL and total or indirect/unconjugated bilirubin above the upper limit of normal).
- 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
- 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:
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.
This study investigates the safety and effectiveness of an investigational medication given as subcutaneous injections to adults with warm autoimmune hemolytic anemia (wAIHA). wAIHA is a condition where the immune system mistakenly attacks the body's red blood cells, causing them to break down too quickly. The study has two parts: Part A focuses on safety and how well the body tolerates the medication, while Part B looks at how well the medication works at a selected dose.
Participants in the study will receive subcutaneous injections. The study will measure various outcomes, including the medication's effect on blood markers related to hemolysis (the breakdown of red blood cells) and its impact on fatigue levels. The study will also evaluate how long the response to the medication lasts and how quickly it begins to work. Some participants may receive a placebo, which is an inactive substance that looks like the investigational medication but does not contain any medicine.
- Who can participate: Adults aged 18 years or older with confirmed primary wAIHA or wAIHA associated with systemic lupus erythematosus (SLE) are eligible. Participants must have a hemoglobin level below 10 g/dL, evidence of hemolysis, and prior treatment with corticosteroids or rituximab without sustained success.
- Study details: Participants will receive subcutaneous injections as part of the study. The study will monitor the effects of the investigational medication on blood markers and fatigue levels. Some participants may receive a placebo, an inactive substance that looks like the investigational medication but does not contain any medicine.
- Study timelines: The study will last 28 weeks.