Warm Autoimmune Hemolytic Anemia (wAIHA)Phase 2NCT04661033
Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA)
A Phase 2 study testing Isatuximab SAR650984 in people with Warm Autoimmune Hemolytic Anemia (wAIHA), run by Sanofi at 6 sites in 6 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Warm Autoimmune Hemolytic Anemia (wAIHA)
- What is being tested?
- Isatuximab SAR650984
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 9 Sep 2021to 26 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
United States1 site
Fox Chase Cancer Center Site Number : 8400004
Philadelphia, Pennsylvania, 19111
United Kingdom1 site
Investigational Site Number : 8260001
London, London, City of, NW1 2PG
About this study
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
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
Read more
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
Read the detailed description
28 weeks (including screening)
- Conditions
- Warm Autoimmune Hemolytic Anemia (wAIHA)
- Being tested
- Isatuximab SAR650984
- Keywords
- (wAIHA)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isatuximab SAR650984Drug
Pharmaceutical form:Solution for injection Route of administration: Subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Experimental | 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. Receives: Drug: Isatuximab SAR650984 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Experimental | Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71. Receives: Drug: Isatuximab SAR650984 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Experimental | Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71. Receives: Drug: Isatuximab SAR650984 |
| Part B: Isatuximab up to 560 mg SC Q2W x6 | Experimental | Participants were planned to receive 6 doses of Isatuximab up to 560 mg (4 mL) via SC injection Q2W through Day 71 Receives: Drug: Isatuximab SAR650984 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 85
Secondary outcomes (29)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: Post-dose on Day 1
Part B: Mean Plasma Trough Concentration Of Isatuximab
Blood samples were planned to be collected at the specified timepoints.
Measured: 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.
Measured: Up to Days 169
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start9 Sep 2021
- Primary completion26 Jun 2023
- Study completion26 Jun 2023
Why it stopped: Study discontinuation based on strategic sponsor decision; not driven by any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Warm Autoimmune Hemolytic Anemia (wAIHA)Studies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04661033
- Sponsor's protocol ID
- ACT16832
- Other IDs
- U1111-1255-5350, 2020-003880-24
- Status last verified
- Dec 2024
- First submitted
- 1 Dec 2020
- Last updated
- 5 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04661033
- Acronym / sponsor ID
- ACT16832
- Conditions
- Warm Autoimmune Hemolytic Anemia (wAIHA)
- Keywords
- (wAIHA)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study discontinuation based on strategic sponsor decision; not driven by any safety concerns.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 9 Sep 2021 (actual)
- Primary completion
- 26 Jun 2023 (actual)
- Study completion
- 26 Jun 2023 (actual)
- First posted
- 9 Dec 2020 (actual)
- Results
- Posted 27 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Experimental | Drug: Isatuximab SAR650984Participants 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. |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Experimental | Drug: Isatuximab SAR650984Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71. |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Experimental | Drug: Isatuximab SAR650984Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71. |
| Part B: Isatuximab up to 560 mg SC Q2W x6 | Experimental | Drug: Isatuximab SAR650984Participants were planned to receive 6 doses of Isatuximab up to 560 mg (4 mL) via SC injection Q2W through Day 71 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Participant must be ≥18 to years of age, inclusive, at the time of signing the informed consent.
Key exclusion criteria (14 listed)
- 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.
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isatuximab SAR650984Pharmaceutical form:Solution for injection Route of administration: Subcutaneous | Drug | Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2, Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6, Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6, Part B: Isatuximab up to 560 mg SC Q2W x6 |
Primary outcome
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days
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.
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
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).
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
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.
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
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.
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
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.
Part B: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85
Time frame: 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.
29 secondary outcomes
Part A: Cohorts 2 and 3: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85 And Day 169
Time frame: Day 85 and Day 169
Part A: Cohorts 2 and 3: Percentage Of Participants With Durable Hemoglobin (Hb) Response By Day 169
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Post-dose on Day 1
Part A: Time to Reach Cmax (Tmax) of Isatuximab
Time frame: 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
Time frame: Post-dose on Day 1
Part A: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Isatuximab
Time frame: Post-dose on Day 1
Part A: Mean Plasma Trough Concentration Of Isatuximab
Time frame: Post-dose on Days 15, 29, 43 and 57
Part A: Number Of Participants With Anti-Isatuximab Antibodies
Time frame: Up to Days 169
Part B: Number of Participants With TEAEs And TESAEs
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Part B: Number of Participants With PCSA: Hematology
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 169
Part B: Absolute Change From Baseline In FACIT-Fatigue Scale Score At Day 85 And Day 169
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Part B: Cmax Of Isatuximab
Time frame: Post-dose on Day 1
Part B: AUCtau of Isatuximab
Time frame: Post-dose on Day 1
Part B: Mean Plasma Trough Concentration Of Isatuximab
Time frame: Post-dose on Days 15, 29, 43 and 57
Part B: Number Of Participants With Anti-Isatuximab Antibodies
Time frame: Up to Days 169
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- ACT16832 Plain language Results SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isatuximab SAR650984 in people with Warm Autoimmune Hemolytic Anemia (wAIHA), run by Sanofi at 6 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, France, Germany, Italy, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) (time frame: From first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.