Warm Autoimmune Hemolytic Anemia (wAIHA)
Conditions
Keywords
(wAIHA)
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)
Interventions
Pharmaceutical form:Solution for injection Route of administration: Subcutaneous
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | 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 | 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. |
| Part A: Maximum Observed Concentration (Cmax) Of Isatuximab | Post-dose on Day 1 | 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. |
| Part A: Time to Reach Cmax (Tmax) of Isatuximab | Post-dose on Day 1 | Blood samples were collected at the specified timepoints. Tmax was defined as time to reach Cmax. The non-compartmental PK analysis was performed. |
| 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 | Post-dose on Day 1 | 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. |
| Part A: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Isatuximab | Post-dose on Day 1 | 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. |
| Part A: Mean Plasma Trough Concentration Of Isatuximab | Post-dose on Days 15, 29, 43 and 57 | Blood samples were collected at the specified timepoints. The non-compartmental Pharmacokinetic (PK) analysis was performed |
| Part A: Number Of Participants With Anti-Isatuximab Antibodies | Up to Days 169 | 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. |
| Part B: Number of Participants With TEAEs And TESAEs | From first dose of study drug (Day 1) up to end of study, approximately 169 days | 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. |
| Part B: Number of Participants With PCSA: Hematology | From first dose of study drug (Day 1) up to end of study, approximately 169 days | 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). |
| Part B: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | From first dose of study drug (Day 1) up to end of study, approximately 169 days | 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 |
| Part B: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis | From first dose of study drug (Day 1) up to end of study, approximately 169 days | 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. |
| Part A: Cohorts 2 and 3: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85 And Day 169 | 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 |
| Part B: Percentage Of Participants With Durable Hemoglobin Response By Day 169 | From first dose of study drug (Day 1) up to end of study (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. |
| Part B: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 169 | 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 |
| Part B: Absolute Change From Baseline In FACIT-Fatigue Scale Score At Day 85 And Day 169 | Baseline (Day 1) and 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. |
| Part B: Absolute Change From Baseline In LDH at 1, 2, 4, 8, 12, and 24 Weeks | Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24 | 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 |
| Part B: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24 | 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 |
| Part B: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24 | 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 |
| Part B: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24 | 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 |
| Part B: Cmax Of Isatuximab | Post-dose on Day 1 | Blood samples were planned to be collected at the specified timepoints. Cmax was defined as maximum concentration observed after the first infusion. |
| Part B: AUCtau of Isatuximab | Post-dose on Day 1 | 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. |
| Part B: Mean Plasma Trough Concentration Of Isatuximab | Post-dose on Days 15, 29, 43 and 57 | Blood samples were planned to be collected at the specified timepoints. |
| Part B: Number Of Participants With Anti-Isatuximab Antibodies | Up to Days 169 | 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. |
| Part B: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | From first dose of study drug (Day 1) up to end of study, approximately 169 days | 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. |
| Part A: Cohorts 2 and 3: Percentage Of Participants With Durable Hemoglobin (Hb) Response By Day 169 | From first dose of study drug (Day 1) up to end of study (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. |
| 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 | Baseline (Day 1), 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. |
| Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | 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 | 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. |
| Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | 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 | 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. |
| Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | 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 | 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. |
Countries
France, Germany, Italy, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 6 centers in 6 countries. A total of 10 participants were screened from 09 September 2021 to 19 December 2022, of which 2 participants were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.
Pre-assignment details
A total of 8 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled in the study and included in 3 Cohorts in Part A. The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns. Hence Part B was not conducted, and no analysis was performed.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3 |
| 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. | 3 |
| 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. | 2 |
| 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. | 0 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | As per Principal Investigator (PI) decision | 1 | 0 | 0 | 0 |
| Overall Study | Early discontinuation as per PI | 1 | 0 | 0 | 0 |
| Overall Study | Switch of cohort due to retreatment criteria met | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Total | Part B: Isatuximab up to 560 mg SC Q2W x6 |
|---|---|---|---|---|---|
| Age, Continuous | 44.7 Years STANDARD_DEVIATION 7.6 | 47.5 Years STANDARD_DEVIATION 30.4 | 59.3 Years STANDARD_DEVIATION 24.7 | 50.9 Years STANDARD_DEVIATION 19.3 | — |
| Age, Customized 18 to 64 years | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 0 Participants |
| Age, Customized 65 to 84 years | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 3 Participants | 8 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 0 |
| other Total, other adverse events | 2 / 3 | 2 / 3 | 2 / 2 | 0 / 0 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 1 / 2 | 0 / 0 |
Outcome results
Primary
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.
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: Safety Population included all participants exposed to the IMP (regardless of the amount of treatment administered).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 10 ULN | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 100% change from baseline | 1 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 3 ULN | 1 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 5 ULN | 1 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 30% change from baseline | 2 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | AST: > 3 ULN | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALP: > 1.5 ULN | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Total Bilirubin: > 1.5 ULN | 3 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Total Bilirubin: > 2 ULN | 3 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Sodium: ≤ 129 mmol/L | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Sodium: ≥ 160 mmol/L | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Potassium: < 3 mmol/L | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Potassium: ≥ 5.5 mmol/L | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Glucose: ≤ 3.9 mmol/L and < LLN | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Glucose: ≥ 11.1 mmol/L (unfasted); ≥ 7 mmol/L (fasted) | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 150 µmol/L | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | AST: > 3 ULN | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALP: > 1.5 ULN | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Total Bilirubin: > 1.5 ULN | 2 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Glucose: ≤ 3.9 mmol/L and < LLN | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Total Bilirubin: > 2 ULN | 2 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Sodium: ≤ 129 mmol/L | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 150 µmol/L | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Sodium: ≥ 160 mmol/L | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 30% change from baseline | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Glucose: ≥ 11.1 mmol/L (unfasted); ≥ 7 mmol/L (fasted) | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 100% change from baseline | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Potassium: < 3 mmol/L | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 3 ULN | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 5 ULN | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 10 ULN | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Potassium: ≥ 5.5 mmol/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Sodium: ≥ 160 mmol/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | AST: > 3 ULN | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Potassium: ≥ 5.5 mmol/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 3 ULN | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALP: > 1.5 ULN | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 150 µmol/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 30% change from baseline | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Total Bilirubin: > 1.5 ULN | 2 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Potassium: < 3 mmol/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 10 ULN | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Total Bilirubin: > 2 ULN | 2 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Glucose: ≤ 3.9 mmol/L and < LLN | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Creatinine: ≥ 100% change from baseline | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Sodium: ≤ 129 mmol/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | ALT: > 5 ULN | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters | Glucose: ≥ 11.1 mmol/L (unfasted); ≥ 7 mmol/L (fasted) | 0 Participants |
Primary
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).
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: Safety Population included all participants exposed to the IMP (regardless of the amount of treatment administered).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Erythrocyte Count: ≥ 6 x 10^12/L | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: Decrease from baseline ≥ 20 g/L | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Neutrophils: < 1.5 x 10^9/L (NB); < 1 x 10^9/L (B) | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Platelet Count: < 100 x 10^9/L | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: ≥ 185 g/L (M); ≥ 165 g/L (F), | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Leukocytes: ≥ 16 x 10^9/L | 2 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Platelet Count: ≥ 700 x 10^9/L | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Monocytes: > 0.7 x 10^9/L | 2 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Leukocytes: < 3 x 10^9/L (NB); < 2 x 10^9/L (B) | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hematocrit: ≤ 0.37 v/v (M); ≤ 0.32 v/v (F) | 3 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Eosinophils: > 0.5 x 10^9/L or > ULN (if ULN ≥ 0.5 x 10^9/L) | 1 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: ≤ 115 g/L (M); ≤ 95 g/L (F) | 3 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hematocrit: ≥ 0.55 v/v (M); ≥ 0.5 v/v (F) | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Basophils: > 0.1 x 10^9/L | 2 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Lymphocytes: > 4 x 10^9/L | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Lymphocytes: > 4 x 10^9/L | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: ≤ 115 g/L (M); ≤ 95 g/L (F) | 3 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: ≥ 185 g/L (M); ≥ 165 g/L (F), | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: Decrease from baseline ≥ 20 g/L | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hematocrit: ≤ 0.37 v/v (M); ≤ 0.32 v/v (F) | 3 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hematocrit: ≥ 0.55 v/v (M); ≥ 0.5 v/v (F) | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Erythrocyte Count: ≥ 6 x 10^12/L | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Platelet Count: < 100 x 10^9/L | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Platelet Count: ≥ 700 x 10^9/L | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Leukocytes: < 3 x 10^9/L (NB); < 2 x 10^9/L (B) | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Leukocytes: ≥ 16 x 10^9/L | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Neutrophils: < 1.5 x 10^9/L (NB); < 1 x 10^9/L (B) | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Monocytes: > 0.7 x 10^9/L | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Basophils: > 0.1 x 10^9/L | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Eosinophils: > 0.5 x 10^9/L or > ULN (if ULN ≥ 0.5 x 10^9/L) | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Erythrocyte Count: ≥ 6 x 10^12/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Basophils: > 0.1 x 10^9/L | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Neutrophils: < 1.5 x 10^9/L (NB); < 1 x 10^9/L (B) | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hematocrit: ≥ 0.55 v/v (M); ≥ 0.5 v/v (F) | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hematocrit: ≤ 0.37 v/v (M); ≤ 0.32 v/v (F) | 2 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Lymphocytes: > 4 x 10^9/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: Decrease from baseline ≥ 20 g/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: ≤ 115 g/L (M); ≤ 95 g/L (F) | 2 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Monocytes: > 0.7 x 10^9/L | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Platelet Count: ≥ 700 x 10^9/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Hb: ≥ 185 g/L (M); ≥ 165 g/L (F), | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Leukocytes: < 3 x 10^9/L (NB); < 2 x 10^9/L (B) | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Platelet Count: < 100 x 10^9/L | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Eosinophils: > 0.5 x 10^9/L or > ULN (if ULN ≥ 0.5 x 10^9/L) | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Leukocytes: ≥ 16 x 10^9/L | 1 Participants |
Primary
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.
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: Safety Population included all participants exposed to the IMP (regardless of the amount of treatment administered).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis | pH: ≤ 4.6 | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis | pH: ≥ 8 | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis | pH: ≤ 4.6 | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis | pH: ≥ 8 | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis | pH: ≤ 4.6 | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis | pH: ≥ 8 | 0 Participants |
Primary
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.
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: Safety Population included all participants exposed to the IMP (regardless of the amount of treatment administered).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SSBP: ≤95 mmHg and decrease from baseline ≥20 mmHg | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SSBP: ≥160 mmHg and increase from baseline ≥20 mmHg | 1 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SDBP: ≤45 mmHg and decrease from baseline ≥10 mmHg | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SDBP: ≥ 110 mmHg and increase from baseline ≥ 10 mmHg | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SHR: ≤ 50 bpm and decrease from baseline ≥ 20 bpm | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SHR: ≥ 120 bpm and increase from baseline ≥ 20 bpm | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | Weight: ≥5% decrease from baseline | 0 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | Weight: ≥ 5% increase from baseline | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SDBP: ≤45 mmHg and decrease from baseline ≥10 mmHg | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | Weight: ≥5% decrease from baseline | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SDBP: ≥ 110 mmHg and increase from baseline ≥ 10 mmHg | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SHR: ≤ 50 bpm and decrease from baseline ≥ 20 bpm | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SHR: ≥ 120 bpm and increase from baseline ≥ 20 bpm | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SSBP: ≤95 mmHg and decrease from baseline ≥20 mmHg | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SSBP: ≥160 mmHg and increase from baseline ≥20 mmHg | 0 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | Weight: ≥ 5% increase from baseline | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SDBP: ≤45 mmHg and decrease from baseline ≥10 mmHg | 2 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SSBP: ≥160 mmHg and increase from baseline ≥20 mmHg | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SSBP: ≤95 mmHg and decrease from baseline ≥20 mmHg | 2 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SDBP: ≥ 110 mmHg and increase from baseline ≥ 10 mmHg | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | Weight: ≥5% decrease from baseline | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SHR: ≥ 120 bpm and increase from baseline ≥ 20 bpm | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | SHR: ≤ 50 bpm and decrease from baseline ≥ 20 bpm | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | Weight: ≥ 5% increase from baseline | 1 Participants |
Primary
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.
Time frame: From first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days
Population: Safety Population included all participants exposed to the IMP (regardless of the amount of treatment administered).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 2 Participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 2 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 0 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 2 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 1 Participants |
Primary
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.
Time frame: Day 85
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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.
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
Population: Efficacy population included all participants exposed to the IMP (regardless of the amount of treatment administered). Only those participants with data collected at each specified timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | 0.000 Grams per Liter (g/L) | Standard Deviation 0 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | 0.000 Grams per Liter (g/L) | — |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | 0.000 Grams per Liter (g/L) | Standard Deviation 0 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | 0.000 Grams per Liter (g/L) | Standard Deviation 0 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | 0.000 Grams per Liter (g/L) | Standard Deviation 0 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | 0.000 Grams per Liter (g/L) | Standard Deviation 0 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -0.025 Grams per Liter (g/L) | Standard Deviation 0.035 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | -0.025 Grams per Liter (g/L) | Standard Deviation 0.035 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | 0.030 Grams per Liter (g/L) | Standard Deviation 0.026 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 24 | -0.022 Grams per Liter (g/L) | Standard Deviation 0.038 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -0.016 Grams per Liter (g/L) | Standard Deviation 0.028 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 24 | -0.050 Grams per Liter (g/L) | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | -0.005 Grams per Liter (g/L) | Standard Deviation 0.007 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | -0.010 Grams per Liter (g/L) | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -0.005 Grams per Liter (g/L) | Standard Deviation 0.007 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | 2.995 Grams per Liter (g/L) | Standard Deviation 4.25 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Haptoglobin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | -0.010 Grams per Liter (g/L) | — |
Secondary
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.
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
Population: Efficacy population included all participants exposed to the IMP (regardless of the amount of treatment administered). Only those participants with data collected at each specified timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -342.3 International Units per Liter (IU/L) | Standard Deviation 130.2 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | -134.0 International Units per Liter (IU/L) | Standard Deviation 183.8 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | 13.0 International Units per Liter (IU/L) | Standard Deviation 192.3 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -355.5 International Units per Liter (IU/L) | Standard Deviation 444.8 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | 84.0 International Units per Liter (IU/L) | Standard Deviation 347.5 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | -110.7 International Units per Liter (IU/L) | Standard Deviation 126.5 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -136.0 International Units per Liter (IU/L) | Standard Deviation 349.9 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | -22.0 International Units per Liter (IU/L) | Standard Deviation 201.8 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | -67.3 International Units per Liter (IU/L) | Standard Deviation 81.4 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 24 | 278.7 International Units per Liter (IU/L) | Standard Deviation 601 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -124.0 International Units per Liter (IU/L) | Standard Deviation 133.3 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 24 | -135.0 International Units per Liter (IU/L) | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | -264.0 International Units per Liter (IU/L) | Standard Deviation 196.6 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | -331.5 International Units per Liter (IU/L) | Standard Deviation 236.9 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -234.5 International Units per Liter (IU/L) | Standard Deviation 105.4 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -309.5 International Units per Liter (IU/L) | Standard Deviation 231.2 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Lactate Dehydrogenase (LDH) at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | -146.0 International Units per Liter (IU/L) | — |
Secondary
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.
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
Population: Efficacy population included all participants exposed to the IMP (regardless of the amount of treatment administered). Only those participants with data collected at each specified timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -51.000 10^9 cells per Liter | — |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | 44.000 10^9 cells per Liter | — |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | 43.000 10^9 cells per Liter | — |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -9.000 10^9 cells per Liter | — |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | 86.000 10^9 cells per Liter | — |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | -29.733 10^9 cells per Liter | Standard Deviation 36.258 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -31.733 10^9 cells per Liter | Standard Deviation 84.835 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | -6.133 10^9 cells per Liter | Standard Deviation 33.198 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 24 | -126.933 10^9 cells per Liter | Standard Deviation 70.273 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | -25.533 10^9 cells per Liter | Standard Deviation 49.878 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -36.833 10^9 cells per Liter | Standard Deviation 34.662 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 24 | 9.900 10^9 cells per Liter | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | -158.400 10^9 cells per Liter | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | -347.400 10^9 cells per Liter | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -370.300 10^9 cells per Liter | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -280.300 10^9 cells per Liter | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Reticulocytes at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | -250.600 10^9 cells per Liter | — |
Secondary
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.
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
Population: Efficacy population included all participants exposed to the IMP (regardless of the amount of treatment administered). Only those participants with data collected at each specified timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -18.26 Micromoles per Liter (μmol/L) | Standard Deviation 31.86 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | 0.70 Micromoles per Liter (μmol/L) | Standard Deviation 18.47 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | 2.45 Micromoles per Liter (μmol/L) | Standard Deviation 15.88 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -14.31 Micromoles per Liter (μmol/L) | Standard Deviation 5.89 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | -8.52 Micromoles per Liter (μmol/L) | Standard Deviation 19 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | -6.38 Micromoles per Liter (μmol/L) | Standard Deviation 1.1 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -8.21 Micromoles per Liter (μmol/L) | Standard Deviation 17.53 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | 3.65 Micromoles per Liter (μmol/L) | Standard Deviation 11.83 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | -7.01 Micromoles per Liter (μmol/L) | Standard Deviation 3.12 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 24 | 0.06 Micromoles per Liter (μmol/L) | Standard Deviation 9.08 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -2.00 Micromoles per Liter (μmol/L) | Standard Deviation 1.78 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 24 | 17.00 Micromoles per Liter (μmol/L) | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 1 | -15.00 Micromoles per Liter (μmol/L) | Standard Deviation 2.83 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 2 | -13.00 Micromoles per Liter (μmol/L) | Standard Deviation 4.24 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 4 | -8.50 Micromoles per Liter (μmol/L) | Standard Deviation 7.78 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 8 | -14.50 Micromoles per Liter (μmol/L) | Standard Deviation 10.61 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Absolute Change From Baseline In Total Bilirubin at 1, 2, 4, 8, 12, and 24 Weeks | Pre-dose at Week 12 | -4.00 Micromoles per Liter (μmol/L) | — |
Secondary
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.
Time frame: Post-dose on Day 1
Population: PK population included all participants exposed to the IMP (regardless of the amount of treatment administered), without any major or critical deviations related to IMP administration and for whom the PK data were considered sufficient and interpretable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | 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 | 540 Hours*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 30 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | 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 | 879 Hours*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 99 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | 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 | 23900 Hours*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 41 |
Secondary
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.
Time frame: Post-dose on Day 1
Population: PK population included all participants exposed to the IMP (regardless of the amount of treatment administered), without any major or critical deviations related to IMP administration and for whom the PK data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Isatuximab | 560 Hours*micrograms per milliliter(h*μg/mL) | Standard Deviation 171 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Isatuximab | 1370 Hours*micrograms per milliliter(h*μg/mL) | Standard Deviation 1350 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Isatuximab | 17800 Hours*micrograms per milliliter(h*μg/mL) | — |
Secondary
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.
Time frame: Baseline (Day 1), Day 85 and Day 169
Population: Efficacy population included all participants exposed to the IMP (regardless of the amount of treatment administered). Only those participants with data collected at each specified timepoint are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | 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 | Day 85 | 7.3 Score on a scale | Standard Deviation 9.3 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | 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 | Day 169 | 1.0 Score on a scale | — |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | 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 | Day 85 | 12.0 Score on a scale | — |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | 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 | Day 169 | 4.0 Score on a scale | — |
Secondary
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
Time frame: Day 85 and Day 169
Population: Efficacy population included all participants exposed to the IMP (regardless of the amount of treatment administered).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Cohorts 2 and 3: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85 And Day 169 | Day 85 | 0.0 Percentage of participants |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Cohorts 2 and 3: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85 And Day 169 | Day 169 | 0.0 Percentage of participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Cohorts 2 and 3: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85 And Day 169 | Day 85 | 50.0 Percentage of participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Cohorts 2 and 3: Overall Response Rate (Response [R] Or Complete Response [CR]) At Day 85 And Day 169 | Day 169 | 0.0 Percentage of participants |
Secondary
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.
Time frame: From first dose of study drug (Day 1) up to end of study (Day 169)
Population: Efficacy population included all participants exposed to the IMP (regardless of the amount of treatment administered).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Cohorts 2 and 3: Percentage Of Participants With Durable Hemoglobin (Hb) Response By Day 169 | 0 Percentage of participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Cohorts 2 and 3: Percentage Of Participants With Durable Hemoglobin (Hb) Response By Day 169 | 50 Percentage of participants |
Secondary
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.
Time frame: Post-dose on Day 1
Population: Pharmacokinetic (PK) population included all participants exposed to the IMP (regardless of the amount of treatment administered), without any major or critical deviations related to IMP administration and for whom the PK data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Maximum Observed Concentration (Cmax) Of Isatuximab | 3.64 Micrograms per milliliter (μg/mL) | Standard Deviation 1.19 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Maximum Observed Concentration (Cmax) Of Isatuximab | 7.41 Micrograms per milliliter (μg/mL) | Standard Deviation 6.29 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Maximum Observed Concentration (Cmax) Of Isatuximab | 151 Micrograms per milliliter (μg/mL) | Standard Deviation 121 |
Secondary
Part A: Mean Plasma Trough Concentration Of Isatuximab
Blood samples were collected at the specified timepoints. The non-compartmental Pharmacokinetic (PK) analysis was performed
Time frame: Post-dose on Days 15, 29, 43 and 57
Population: PK population included all participants exposed to the IMP (regardless of the amount of treatment administered), without any major or critical deviations related to IMP administration and for whom the PK data were considered sufficient and interpretable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 15 | 0.0114 Micrograms per milliliter (μg/mL) | Standard Deviation 0.014 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 29 | 0.167 Micrograms per milliliter (μg/mL) | Standard Deviation 0.27 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 43 | 0.00111 Micrograms per milliliter (μg/mL) | Standard Deviation 0.00131 |
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 57 | NA Micrograms per milliliter (μg/mL) | — |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 57 | 10.7 Micrograms per milliliter (μg/mL) | Standard Deviation 4.08 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 15 | 0.678 Micrograms per milliliter (μg/mL) | Standard Deviation 0.994 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 43 | 6.69 Micrograms per milliliter (μg/mL) | Standard Deviation 5.9 |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 29 | 7.30 Micrograms per milliliter (μg/mL) | Standard Deviation 7.13 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 57 | 146 Micrograms per milliliter (μg/mL) | — |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 29 | 134 Micrograms per milliliter (μg/mL) | Standard Deviation 62.3 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 43 | 62.0 Micrograms per milliliter (μg/mL) | Standard Deviation 87.7 |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Mean Plasma Trough Concentration Of Isatuximab | Day 15 | 140 Micrograms per milliliter (μg/mL) | Standard Deviation 137 |
Secondary
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.
Time frame: Up to Days 169
Population: ADA population included all participants exposed to the IMP (regardless of the amount of treatment administered) with at least one evaluable ADA sample (positive, negative or inconclusive) during the treatment emergent (TE) period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Number Of Participants With Anti-Isatuximab Antibodies | 1 Participants |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Number Of Participants With Anti-Isatuximab Antibodies | 1 Participants |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Number Of Participants With Anti-Isatuximab Antibodies | 0 Participants |
Secondary
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.
Time frame: Post-dose on Day 1
Population: PK population included all participants exposed to the IMP (regardless of the amount of treatment administered), without any major or critical deviations related to IMP administration and for whom the PK data were considered sufficient and interpretable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 | Part A: Time to Reach Cmax (Tmax) of Isatuximab | 89.50 Hours (h) |
| Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 | Part A: Time to Reach Cmax (Tmax) of Isatuximab | 92.68 Hours (h) |
| Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 | Part A: Time to Reach Cmax (Tmax) of Isatuximab | 202.69 Hours (h) |
Secondary
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.
Time frame: Baseline (Day 1) and Day 85 and Day 169
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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
Time frame: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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
Time frame: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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
Time frame: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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
Time frame: Baseline (Day 1) and pre-dose at Weeks 1, 2, 4, 8, 12, and 24
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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.
Time frame: Post-dose on Day 1
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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.
Time frame: Post-dose on Day 1
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
Part B: Mean Plasma Trough Concentration Of Isatuximab
Blood samples were planned to be collected at the specified timepoints.
Time frame: Post-dose on Days 15, 29, 43 and 57
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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.
Time frame: Up to Days 169
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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).
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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.
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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.
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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.
Time frame: From first dose of study drug (Day 1) up to end of study, approximately 169 days
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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
Time frame: Day 169
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.
Secondary
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.
Time frame: From first dose of study drug (Day 1) up to end of study (Day 169)
Population: The study was prematurely terminated based on strategic sponsor decision during Part A; not driven by any safety concerns, hence Part B was not conducted, and no analysis was performed.