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

Warm Autoimmune Hemolytic Anemia (wAIHA) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04661033
• Other study ID #: ACT16832
• Secondary ID: 2020-003880-24U1
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 9, 2021
• Est. completion date: June 26, 2023

Study information

• Verified date: July 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

28 weeks (including screening)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: June 26, 2023
• Est. primary completion date: June 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Hemolysis
• Warm Autoimmune Hemolytic Anemia (wAIHA)

Intervention

Drug:
• Isatuximab SAR650984
Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Locations

Country	Name	City	State
Belgium	Investigational Site Number :0560001	Leuven
France	Investigational Site Number :2500001	Creteil Cedex
France	Investigational Site Number :2500002	Pessac
Germany	Investigational Site Number :2760001 Universitätsklinikum Essen Klinik für Hämatologie und Stammzellentransplantation	Essen
Hungary	Investigational Site Number :3480001 Egyetem ÁOK, Belgyógyászati és Onkológiai Klinika, Klinikai Farmakológiai Részleg	Budapest
Italy	Investigational Site Number :3800001 Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35	Milano
Netherlands	Investigational Site Number :5280001	Leiden
United Kingdom	Investigational Site Number :8260001	London	London, City Of
United States	University of Southern California-Site Number:8400001	Los Angeles	California
United States	Fox Chase Cancer Center-Site Number:8400004	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A To assess safety and tolerability	Standard clinical and laboratory parameters and adverse events.	Through Day 169
Primary	Part B -To evaluate overall response rate (R) or complete response (CR) at Day 85	R is defined as an increase in hemoglobin by =2 g/dL from baseline and an absence of transfusion in the last 7 days and absence of rescue medications in the past 4 weeks. Biochemical evidence of hemolysis may still be present.; CR is defined as hemoglobin =11 g/dL (women) or =12 g/dL (men), no evidence of hemolysis (normal bilirubin, LDH, haptoglobin, and reticulocytes), absence of transfusion in the last 7 days and absence of rescue medication in the past 4 weeks	Through Day 85
Secondary	Part A (Cohorts 2 and 3 Only) -To evaluate overall response rate (R) or complete response (CR) at Day 85	R is defined as an increase in hemoglobin by =2 g/dL from baseline and an absence of transfusion in the last 7 days and absence of rescue medications in the past 4 weeks. Biochemical evidence of hemolysis may still be present.; CR is defined as hemoglobin =11 g/dL (women) or =12 g/dL(men), no evidence of hemolysis (normal bilirubin, LDH, haptoglobin, and reticulocytes), and absence of transfusion in the last 7 days and absence of rescue medication in the past 4 weeks.	Through Day 85
Secondary	Part A (Cohorts 2 and 3 Only) and Part B -Proportion of participants with durable hemoglobin response by Day 169	Durable response is defined as Hb level =10 g/dL with an increase from baseline of =2 g/dL on three consecutive evaluable visits during the study period; with absence of transfusion and no rescue medication during the period of 3 consecutive visits and for at least 7 days (transfusions) and 4 weeks (rescue medication) prior to the first consecutive visit.	Through Day 169
Secondary	Part A (Cohorts 2 and 3 Only) and Part B -Overall response rate at Day 169	Overall response rate at Day 169, median time to R or CR, median time to loss of R or CR (loss of R defined as hemoglobin <10 g/dL at two consecutive visits at least 7 days apart and initiation of new treatment for anemia or increase in steroid dose; loss of CR is defined as hemoglobin <11 g/dL (women) or <12 g/dL (men) at two consecutive visits at least 7 days apart), proportion of participants requiring rescue therapy (any wAIHAdirected therapy other than prednisone or transfusion) or splenectomy	Through Day 169
Secondary	Part A (Cohorts 2 and 3 Only) and Part B -FACIT-fatigue scale score	-FACIT-fatigue scale score	Through Day 169
Secondary	Part B -To assess safety and tolerability	Standard clinical and laboratory parameters and adverse events.	Through Day 169
Secondary	Part A (All Cohorts) and B -Change from baseline in LDH		Through Day 169
Secondary	Part A (All Cohorts) and B -Change from baseline in haptoglobin		Through Day 169
Secondary	Part A (All Cohorts) and B -Change from baseline in reticulocytes		Through Day 169
Secondary	Part A (All Cohorts) and B -Change from baseline in total bilirubin		Through Day 169
Secondary	Part A (All Cohorts) and B -PK parameters after subcutaneous administrations (Cmax)	Maximum concentration received after injection (Cmax)	Through Day 169
Secondary	Part A (All Cohorts) and B -PK parameters after subcutaneous administrations (AUC0-2week)	Area under the plasma concentration versus time curve calculated over the dosing interval T (336 h) (AUC0-2week)	Through Day 169
Secondary	Part A (All Cohorts) and B Incidence of anti-isatuximab antibodies		Through Day 169
Secondary	Part A (All Cohorts) and B Titer (if relevant) of anti-isatuximab antibodies		Through Day 169