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

NCT ID: NCT04661033

Last Updated: 2024-12-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-09
• Study Completion Date: 2023-06-26

Brief Summary

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

Detailed Description

28 weeks (including screening)

Conditions

Warm Autoimmune Hemolytic Anemia (wAIHA)

Keywords

(wAIHA)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2

Participants received 2 doses of Isatuximab 140 milligrams (mg) (1 milliliter \[mL\]) via subcutaneous (SC) injection every 2 weeks (Q2W) on Day 1 and Day 15.

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6

Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6

Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Part B: Isatuximab up to 560 mg SC Q2W x6

Participants were planned to receive 6 doses of Isatuximab up to 560 mg (4 mL) via SC injection Q2W through Day 71

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Interventions

Isatuximab SAR650984

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Fox Chase Cancer Center Site Number : 8400004

Philadelphia, Pennsylvania, United States

Investigational Site Number : 2500001

Créteil, , France

Investigational Site Number : 2760001

Essen, , Germany

Investigational Site Number : 3800001

Milan, , Italy

Investigational Site Number : 5280001

Leiden, , Netherlands

Investigational Site Number : 8260001

London, London, City of, United Kingdom

Countries

Belgium; Hungary; United States; France; Germany; Italy; Netherlands; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://sanofi.trialsummaries.com/Study/StudyDetails?id=25198&tenant=MT_SNY_9011

ACT16832 Plain language Results Summary

Other Identifiers

U1111-1255-5350

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-003880-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACT16832

Identifier Type: -

Identifier Source: org_study_id