Back to resultsSafety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA)
Primary Purpose
Warm Autoimmune Hemolytic Anemia (wAIHA)
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Isatuximab SAR650984
Sponsored by
About this trial
This is an interventional treatment trial for Warm Autoimmune Hemolytic Anemia (wAIHA) focused on measuring (wAIHA)
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:
- 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
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.
Sites / Locations
- University of Southern California-Site Number:8400001
- Fox Chase Cancer Center-Site Number:8400004
- Investigational Site Number :0560001
- Investigational Site Number :2500001
- Investigational Site Number :2500002
- Investigational Site Number :2760001 Universitätsklinikum Essen Klinik für Hämatologie und Stammzellentransplantation
- Investigational Site Number :3480001 Egyetem ÁOK, Belgyógyászati és Onkológiai Klinika, Klinikai Farmakológiai Részleg
- Investigational Site Number :3800001 Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35
- Investigational Site Number :5280001
- Investigational Site Number :8260001
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Isatuximab Part A/Cohort 1
Isatuximab Part A/Cohort 2
Isatuximab Part A/Cohort 3 (optional)
Isatuximab Part B
Arm Description
Isatuximab dose subcutaneous (SC) every 2 weeks x 2 doses
Isatuximab dose subcutaneous (SC) every 2 weeks x 6 doses
Isatuximab dose subcutaneous (SC) every 2 weeks x 2 doses
Isatuximab dose subcutaneous (SC) every 2 weeks x 6 doses
Outcomes
Primary Outcome Measures
Part A To assess safety and tolerability
Standard clinical and laboratory parameters and adverse events.
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
Secondary Outcome Measures
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.
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.
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
Part A (Cohorts 2 and 3 Only) and Part B -FACIT-fatigue scale score
-FACIT-fatigue scale score
Part B -To assess safety and tolerability
Standard clinical and laboratory parameters and adverse events.
Part A (All Cohorts) and B -Change from baseline in LDH
Part A (All Cohorts) and B -Change from baseline in haptoglobin
Part A (All Cohorts) and B -Change from baseline in reticulocytes
Part A (All Cohorts) and B -Change from baseline in total bilirubin
Part A (All Cohorts) and B -PK parameters after subcutaneous administrations (Cmax)
Maximum concentration received after injection (Cmax)
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)
Part A (All Cohorts) and B Incidence of anti-isatuximab antibodies
Part A (All Cohorts) and B Titer (if relevant) of anti-isatuximab antibodies
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04661033
Brief Title
Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA)
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Study discontinuation based on strategic sponsor decision; not driven by any safety concerns.
Study Start Date
September 9, 2021 (Actual)
Primary Completion Date
June 26, 2023 (Actual)
Study Completion Date
June 26, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Warm Autoimmune Hemolytic Anemia (wAIHA)
Keywords
(wAIHA)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Isatuximab Part A/Cohort 1
Arm Type
Experimental
Arm Description
Isatuximab dose subcutaneous (SC) every 2 weeks x 2 doses
Arm Title
Isatuximab Part A/Cohort 2
Arm Type
Experimental
Arm Description
Isatuximab dose subcutaneous (SC) every 2 weeks x 6 doses
Arm Title
Isatuximab Part A/Cohort 3 (optional)
Arm Type
Experimental
Arm Description
Isatuximab dose subcutaneous (SC) every 2 weeks x 2 doses
Arm Title
Isatuximab Part B
Arm Type
Experimental
Arm Description
Isatuximab dose subcutaneous (SC) every 2 weeks x 6 doses
Intervention Type
Drug
Intervention Name(s)
Isatuximab SAR650984
Intervention Description
Pharmaceutical form:Solution for injection Route of administration: Subcutaneous
Primary Outcome Measure Information:
Title
Part A To assess safety and tolerability
Description
Standard clinical and laboratory parameters and adverse events.
Time Frame
Through Day 169
Title
Part B -To evaluate overall response rate (R) or complete response (CR) at Day 85
Description
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
Time Frame
Through Day 85
Secondary Outcome Measure Information:
Title
Part A (Cohorts 2 and 3 Only) -To evaluate overall response rate (R) or complete response (CR) at Day 85
Description
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.
Time Frame
Through Day 85
Title
Part A (Cohorts 2 and 3 Only) and Part B -Proportion of participants with durable hemoglobin response by Day 169
Description
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.
Time Frame
Through Day 169
Title
Part A (Cohorts 2 and 3 Only) and Part B -Overall response rate at Day 169
Description
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
Time Frame
Through Day 169
Title
Part A (Cohorts 2 and 3 Only) and Part B -FACIT-fatigue scale score
Description
-FACIT-fatigue scale score
Time Frame
Through Day 169
Title
Part B -To assess safety and tolerability
Description
Standard clinical and laboratory parameters and adverse events.
Time Frame
Through Day 169
Title
Part A (All Cohorts) and B -Change from baseline in LDH
Time Frame
Through Day 169
Title
Part A (All Cohorts) and B -Change from baseline in haptoglobin
Time Frame
Through Day 169
Title
Part A (All Cohorts) and B -Change from baseline in reticulocytes
Time Frame
Through Day 169
Title
Part A (All Cohorts) and B -Change from baseline in total bilirubin
Time Frame
Through Day 169
Title
Part A (All Cohorts) and B -PK parameters after subcutaneous administrations (Cmax)
Description
Maximum concentration received after injection (Cmax)
Time Frame
Through Day 169
Title
Part A (All Cohorts) and B -PK parameters after subcutaneous administrations (AUC0-2week)
Description
Area under the plasma concentration versus time curve calculated over the dosing interval T (336 h) (AUC0-2week)
Time Frame
Through Day 169
Title
Part A (All Cohorts) and B Incidence of anti-isatuximab antibodies
Time Frame
Through Day 169
Title
Part A (All Cohorts) and B Titer (if relevant) of anti-isatuximab antibodies
Time Frame
Through Day 169
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
University of Southern California-Site Number:8400001
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Fox Chase Cancer Center-Site Number:8400004
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Investigational Site Number :0560001
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigational Site Number :2500001
City
Creteil Cedex
ZIP/Postal Code
94010
Country
France
Facility Name
Investigational Site Number :2500002
City
Pessac
ZIP/Postal Code
33600
Country
France
Facility Name
Investigational Site Number :2760001 Universitätsklinikum Essen Klinik für Hämatologie und Stammzellentransplantation
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Investigational Site Number :3480001 Egyetem ÁOK, Belgyógyászati és Onkológiai Klinika, Klinikai Farmakológiai Részleg
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Investigational Site Number :3800001 Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Investigational Site Number :5280001
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Investigational Site Number :8260001
City
London
State/Province
London, City Of
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Learn more about this trial
Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA)
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