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

Study Overview

• Status: Terminated
• Conditions: Warm Autoimmune Hemolytic Anemia (wAIHA)
• Intervention / Treatment: Drug: Isatuximab SAR650984

Detailed Description

28 weeks (including screening)

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Creteil Cedex, France, 94010
    • Investigational Site Number : 2500001
• Germany
  • Essen, Germany, 45147
    • Investigational Site Number : 2760001
• Italy
  • Milano, Italy, 20122
    • Investigational Site Number : 3800001
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Investigational Site Number : 5280001
• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, NW1 2PG
      • Investigational Site Number : 8260001
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center Site Number : 8400004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Isatuximab SAR650984; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous
Experimental: 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.	Drug: Isatuximab SAR650984; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous
Experimental: 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.	Drug: Isatuximab SAR650984; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous
Experimental: 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	Drug: Isatuximab SAR650984; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE is defined as an AE that occurred from the time of the first IMP administration up to 30 days (included) after the last IMP administration. A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.	From first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology	Blood samples were collected to determine the hematology laboratory significant abnormalities. PCSA values: abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Hemoglobin (Hb): ≤ 115 grams per Liter (g/L) (Male[M]); ≤ 95 g/L (Female[F]), ≥ 185 g/L (M); ≥ 165 g/L (F), Decrease from baseline ≥ 20 g/L; Hematocrit: ≤ 0.37 volume per volume (v/v) (M); ≤ 0.32 v/v (F), ≥ 0.55 v/v (M); ≥ 0.5 v/v (F); Erythrocyte Count: ≥ 6 x 10^12 per Liter (/L); Platelet count: < 100 x 10^9/L, ≥ 700 x 10^9/L; Leukocytes: < 3 x 10^9/L (Non-Black [NB]); < 2 x 10^9/L (Black [B]), ≥ 16 x 10^9/L; Neutrophils: < 1.5 x 10^9/L (B); < 1 x 10^9/L (B); Lymphocytes: > 4 x 10^9/L; Monocytes: > 0.7 x 10^9/L; Basophils: > 0.1 x 10^9/L; Eosinophils: > 0.5 x 10^9/L or > Upper limit of Normal (ULN) (if ULN ≥ 0.5 x 10^9/L).	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters	Blood samples were collected to determine the clinical chemistry laboratory and electrolyte parameters significant abnormalities. PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Glucose: ≤ 3.9 millimoles per Liter (mmol/L) and < Lower limit of normal (LLN), ≥ 11.1 mmol/L (unfasted); ≥ 7 mmol/L (fasted); Creatinine: ≥ 150 micromoles (µmol)/L, ≥ 30% change from baseline, ≥ 100% change from baseline, Alanine Aminotransferase (ALT): > 3 ULN, > 5 ULN, > 10 ULN; Aspartate Aminotransferase (AST): > 3 ULN; Alkaline Phosphatase (ALP): > 1.5 ULN; Total Bilirubin: > 1.5 ULN, > 2 ULN; Sodium: ≤ 129 mmol/L, ≥ 160 mmol/L and Potassium: < 3 mmol/L, ≥ 5.5 mmol/L.	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis	Urine samples were collected to determine the urinalysis parameter significant abnormalities. PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: pH: ≤ 4.6 or ≥ 8.	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs	Vital signs were examined to determine the abnormalities. Vital signs included Sitting systolic blood pressure (SSBP), Sitting diastolic blood pressure (SDBP), Sitting heart rate (SHR) and weight. PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: SSBP: ≤95 millimeters of mercury (mmHg) and decrease from baseline ≥20 mmHg; ≥160 mmHg and increase from baseline ≥20 mmHg; SDBP: ≤45 mmHg and decrease from baseline ≥10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; SHR: ≤ 50 beats per minute (bpm) and decrease from baseline ≥ 20 bpm, ≥120 bpm and increase from baseline ≥ 20 bpm; Weight: ≥ 5% decrease from baseline, ≥5% increase from baseline.	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part B: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85	Overall response rate was defined as the percentage of participants with a response (R) or complete response (CR) over the evaluable participants. R was defined as an increase in Hb 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 might still be present. CR was defined as Hb ≥11 g/dL (women) or ≥12 g/dL (men), no evidence of hemolysis (normal bilirubin, Lactate dehydrogenase [LDH], haptoglobin, and reticulocytes), and absence of transfusion in the last 7 days and absence of rescue medication in the past 4 weeks.	Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Cohorts 2 and 3: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85 And Day 169	Overall response rate was defined as the percentage of participants with a R or CR over the evaluable participants. R was defined as an increase in Hb 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 might still be present. CR was defined as Hb ≥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	Day 85 and Day 169
Part A: Cohorts 2 and 3: Percentage Of Participants With Durable Hemoglobin (Hb) Response By Day 169	Durable response was 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.	From first dose of study drug (Day 1) up to end of study (Day 169)
Part A: Cohorts 2 and 3: Absolute Change From Baseline in Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scale Score At Day 85 and Day 169	The FACIT-Fatigue scale is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0 to 4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52, where higher score (and positive change scores) indicated better functioning. Baseline was defined as the Day 1 pre-dose value.	Baseline (Day 1), Day 85 and Day 169
Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks	Blood samples were collected to evaluate the effect of Isatuximab on marker of hemolysis: LDH. Baseline is defined as the last assessment value before IMP.	Cohort 1 : Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, and 12; Cohorts 2 and 3: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks	Blood samples were collected to evaluate the effect of Isatuximab on marker of hemolysis: Haptoglobin. Baseline was defined as the last assessment value before IMP.	Cohort 1 : Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, and 12; Cohorts 2 and 3: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks	Blood samples were collected to evaluate the effect of Isatuximab on marker of hemolysis: Reticulocytes. Baseline was defined as the last assessment value before IMP.	Cohort 1 : Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, and 12; Cohorts 2 and 3: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks	Blood samples were collected to evaluate the effect of Isatuximab on marker of hemolysis: Total Bilirubin. Baseline was defined as the last assessment value before IMP.	Cohort 1 : Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, and 12; Cohorts 2 and 3: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part A: Maximum Observed Concentration (Cmax) Of Isatuximab	Blood samples were collected at the specified timepoints. Cmax was defined as maximum concentration observed after the first infusion. The non-compartmental pharmacokinetic (PK) analysis was performed.	Post-dose on Day 1
Part A: Time to Reach Cmax (Tmax) of Isatuximab	Blood samples were collected at the specified timepoints. Tmax was defined as time to reach Cmax. The non-compartmental PK analysis was performed.	Post-dose on Day 1
Part A: Area Under the Plasma Concentration Versus Time Curve Calculated Using the Trapezoidal Method From Time Zero to Time of the Last Concentration Observed Above the Lower Limit of Quantification (Clast) (AUClast) of Isatuximab	Blood samples were collected at the specified timepoints. AUClast was defined as area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the Clast. The non-compartmental PK analysis was performed.	Post-dose on Day 1
Part A: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Isatuximab	Blood samples were collected at the specified timepoints. AUCtau was defined as area under the plasma concentration versus time curve over the dosing interval. The non-compartmental PK analysis was performed.	Post-dose on Day 1
Part A: Mean Plasma Trough Concentration Of Isatuximab	Blood samples were collected at the specified timepoints. The non-compartmental Pharmacokinetic (PK) analysis was performed	Post-dose on Days 15, 29, 43 and 57
Part A: Number Of Participants With Anti-Isatuximab Antibodies	Plasma samples were collected to evaluate antibodies to Isatuximab. Plasma samples were screened for antibodies binding to Isatuximab. Post-baseline positive, defined as Anti-drug antibody (ADA) that developed at any time during the ADA on-study observation period in participants without pre-existing ADA. Number of participants with positive ADA have been reported.	Up to Days 169
Part B: Number of Participants With TEAEs And TESAEs	An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE is defined as an AE that occurred from the time of the first IMP administration up to 30 days (included) after the last IMP administration. A SAE is defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part B: Number of Participants With PCSA: Hematology	Blood samples were planned to be collected to determine the hematology laboratory significant abnormalities. PCSA values: abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Hb: ≤ 115 g/L (M); ≤ 95 g/L (F), ≥ 185 g/L (M); ≥ 165 g/L (F), Decrease from baseline ≥ 20 g/L; Hematocrit: ≤ 0.37 v/v (M); ≤ 0.32 v/v (F), ≥ 0.55 v/v (M); ≥ 0.5 v/v (F); Erythrocyte Count: ≥ 6 x 10^12/L); Platelet count: < 100 x 10^9/L, ≥ 700 x 10^9/L; Leukocytes: < 3 x 10^9/L (NB); < 2 x 10^9/L (B), ≥ 16 x 10^9/L; Neutrophils: < 1.5 x 10^9/L (B); < 1 x 10^9/L (B); Lymphocytes: > 4 x 10^9/L; Monocytes: > 0.7 x 10^9/L; Basophils: > 0.1 x 10^9/L; Eosinophils: > 0.5 x 10^9/L or > ULN (if ULN ≥ 0.5 x 10^9/L).	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part B: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters	Blood samples were planned to be collected to determine the clinical chemistry laboratory and electrolyte parameters significant abnormalities. PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Glucose: ≤ 3.9 mmol/L and < LLN, ≥ 11.1 mmol/L (unfasted); ≥ 7 mmol/L (fasted); Creatinine: ≥ 150 µmol/L, ≥ 30% change from baseline, ≥ 100% change from baseline, ALT: > 3 ULN, > 5 ULN, > 10 ULN; AST: > 3 ULN; ALP: > 1.5 ULN; Total Bilirubin: > 1.5 ULN, > 2 ULN; Sodium: ≤ 129 mmol/L; ≥ 160 mmol/L; Potassium: < 3 mmol/L, ≥ 5.5 mmol/L and Calcium	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part B: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis	Urine samples were planned to be collected to determine the urinalysis parameter significant abnormalities. PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: pH ≤ 4.6 or ≥ 8.	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part B: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs	Vital signs were planned to be examined to determine the abnormalities. Vital signs included SSBP, SDBP, SHR and weight. PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: SSBP: ≤ 95 mmHg and decrease from baseline ≥ 20 mmHg, ≥ 160 mmHg and increase from baseline ≥20 mmHg; SDBP: ≤ 45 mmHg and decrease from baseline ≥ 10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; SHR: ≤ 50 bpm and decrease from baseline ≥ 20 bpm, ≥ 120 bpm and increase from baseline ≥ 20 bpm; Weight: ≥ 5% decrease from baseline, ≥5% increase from baseline.	From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part B: Percentage Of Participants With Durable Hemoglobin Response By Day 169	Durable response was 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.	From first dose of study drug (Day 1) up to end of study (Day 169)
Part B: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 169	Overall response rate was defined as the percentage of participants with a R or CR over the evaluable participants. R was defined as an increase in Hb 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 might still be present. CR was defined as Hb ≥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	Day 169
Part B: Absolute Change From Baseline In FACIT-Fatigue Scale Score At Day 85 And Day 169	The FACIT-Fatigue scale is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0 to 4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52, where higher score (and positive change scores) indicated better functioning. Baseline was defined as the Day 1 pre-dose value.	Baseline (Day 1) and Day 85 and Day 169
Part B: Absolute Change From Baseline In LDH at 1, 2, 4, 8, 12, and 24 Weeks	Blood samples were planned to be collected to evaluate the effect of Isatuximab on marker of hemolysis: LDH. Baseline was defined as the last assessment value before IMP	Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part B: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks	Blood samples were planned to be collected to evaluate the effect of Isatuximab on marker of hemolysis: Haptoglobin. Baseline was defined as the last assessment value before IMP	Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part B: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks	Blood samples were planned to be collected to evaluate the effect of Isatuximab on marker of hemolysis: Reticulocytes. Baseline was defined as the last assessment value before IMP	Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part B: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks	Blood samples were planned to be collected to evaluate the effect of Isatuximab on marker of hemolysis: Total Bilirubin. Baseline was defined as the last assessment value before IMP	Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part B: Cmax Of Isatuximab	Blood samples were planned to be collected at the specified timepoints. Cmax was defined as maximum concentration observed after the first infusion.	Post-dose on Day 1
Part B: AUCtau of Isatuximab	Blood samples were planned to be collected at the specified timepoints. AUCtau was defined as area under the plasma concentration versus time curve over the dosing interval.	Post-dose on Day 1
Part B: Mean Plasma Trough Concentration Of Isatuximab	Blood samples were planned to be collected at the specified timepoints.	Post-dose on Days 15, 29, 43 and 57
Part B: Number Of Participants With Anti-Isatuximab Antibodies	Plasma samples were planned to be collected to evaluate antibodies to Isatuximab. Plasma samples were planned to be screened for antibodies binding to Isatuximab. Post-baseline positive, defined as ADA that developed at any time during the ADA on-study observation period in participants without pre-existing ADA.	Up to Days 169

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

Helpful Links

• ACT16832 Plain language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Actual): June 26, 2023
• Study Completion (Actual): June 26, 2023

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: (wAIHA)
• Additional Relevant MeSH Terms: Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: ACT16832; 2020-003880-24 (EudraCT Number); U1111-1255-5350 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No