Trial Outcomes & Findings for Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA) (NCT NCT04661033)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

From first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days

Results posted on

2024-12-05

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	3	3	2
Overall Study Participants Who Completed the Study Treatment Period	3	2	1
Overall Study COMPLETED	0	3	1
Overall Study NOT COMPLETED	3	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	0	1
Overall Study Switch of cohort due to retreatment criteria met	1	0
Overall Study As per Principal Investigator (PI) decision	1	0
Overall Study Early discontinuation as per PI	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.	Part B: Isatuximab up to 560 mg SC Q2W x6 Participants were planned to receive 6 doses of Isatuximab up to 560 mg (4 mL) via SC injection Q2W through Day 71.	Total n=8 Participants Total of all reporting groups
Age, Continuous	59.3 Years STANDARD_DEVIATION 24.7 • n=5 Participants	44.7 Years STANDARD_DEVIATION 7.6 • n=7 Participants	47.5 Years STANDARD_DEVIATION 30.4 • n=5 Participants	—	50.9 Years STANDARD_DEVIATION 19.3 • n=21 Participants
Age, Customized 18 to 64 years	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Age, Customized 65 to 84 years	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) Any TEAEs	2 Participants	2 Participants	2 Participants
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) Any TESAEs	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Hb: ≤ 115 g/L (M); ≤ 95 g/L (F)	3 Participants	3 Participants	2 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Hb: ≥ 185 g/L (M); ≥ 165 g/L (F),	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Hb: Decrease from baseline ≥ 20 g/L	0 Participants	1 Participants	0 Participants
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	3 Participants	2 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Erythrocyte Count: ≥ 6 x 10^12/L	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Platelet Count: < 100 x 10^9/L	0 Participants	0 Participants	0 Participants
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	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Platelet Count: ≥ 700 x 10^9/L	0 Participants	1 Participants	0 Participants
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	0 Participants	1 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Leukocytes: ≥ 16 x 10^9/L	2 Participants	1 Participants	1 Participants
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	0 Participants	1 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Lymphocytes: > 4 x 10^9/L	1 Participants	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Monocytes: > 0.7 x 10^9/L	2 Participants	1 Participants	1 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology Basophils: > 0.1 x 10^9/L	2 Participants	1 Participants	1 Participants
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	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Glucose: ≤ 3.9 mmol/L and < LLN	0 Participants	0 Participants	1 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Glucose: ≥ 11.1 mmol/L (unfasted); ≥ 7 mmol/L (fasted)	0 Participants	1 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Creatinine: ≥ 150 µmol/L	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters ALT: > 5 ULN	1 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters ALT: > 10 ULN	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters AST: > 3 ULN	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters ALP: > 1.5 ULN	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Total Bilirubin: > 1.5 ULN	3 Participants	2 Participants	2 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Total Bilirubin: > 2 ULN	3 Participants	2 Participants	2 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Sodium: ≤ 129 mmol/L	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Sodium: ≥ 160 mmol/L	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Potassium: < 3 mmol/L	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Potassium: ≥ 5.5 mmol/L	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Creatinine: ≥ 30% change from baseline	2 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters Creatinine: ≥ 100% change from baseline	1 Participants	0 Participants	0 Participants
Part A: Number of Participants With PCSA: Clinical Chemistry And Electrolyte Parameters ALT: > 3 ULN	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis pH: ≤ 4.6	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis pH: ≥ 8	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs SSBP: ≤95 mmHg and decrease from baseline ≥20 mmHg	0 Participants	0 Participants	2 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs SDBP: ≥ 110 mmHg and increase from baseline ≥ 10 mmHg	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs SHR: ≤ 50 bpm and decrease from baseline ≥ 20 bpm	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs Weight: ≥5% decrease from baseline	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs Weight: ≥ 5% increase from baseline	1 Participants	0 Participants	1 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs SSBP: ≥160 mmHg and increase from baseline ≥20 mmHg	1 Participants	0 Participants	0 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs SDBP: ≤45 mmHg and decrease from baseline ≥10 mmHg	0 Participants	0 Participants	2 Participants
Part A: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs SHR: ≥ 120 bpm and increase from baseline ≥ 20 bpm	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 85 and Day 169

Population: Efficacy population included all participants exposed to the IMP (regardless of the amount of treatment administered).

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

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
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	0.0 Percentage of participants	—
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	50.0 Percentage of participants	—

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Cohorts 2 and 3: Percentage Of Participants With Durable Hemoglobin (Hb) Response By Day 169	0 Percentage of participants	50 Percentage of participants	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
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	12.0 Score on a scale Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	—
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 Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	4.0 Score on a scale Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
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	-110.7 International Units per Liter (IU/L) Standard Deviation 126.5	-331.5 International Units per Liter (IU/L) Standard Deviation 236.9
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	-22.0 International Units per Liter (IU/L) Standard Deviation 201.8	-146.0 International Units per Liter (IU/L) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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 601.0	-135.0 International Units per Liter (IU/L) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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	-67.3 International Units per Liter (IU/L) Standard Deviation 81.4	-264.0 International Units per Liter (IU/L) Standard Deviation 196.6
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	-124.0 International Units per Liter (IU/L) Standard Deviation 133.3	-234.5 International Units per Liter (IU/L) Standard Deviation 105.4
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	-136.0 International Units per Liter (IU/L) Standard Deviation 349.9	-309.5 International Units per Liter (IU/L) Standard Deviation 231.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
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 0.000	-0.016 Grams per Liter (g/L) Standard Deviation 0.028	-0.005 Grams per Liter (g/L) Standard Deviation 0.007
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 0.000	-0.025 Grams per Liter (g/L) Standard Deviation 0.035	2.995 Grams per Liter (g/L) Standard Deviation 4.250
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) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	-0.025 Grams per Liter (g/L) Standard Deviation 0.035	-0.010 Grams per Liter (g/L) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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	-0.050 Grams per Liter (g/L) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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 0.000	0.030 Grams per Liter (g/L) Standard Deviation 0.026	-0.005 Grams per Liter (g/L) Standard Deviation 0.007
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 0.000	0.000 Grams per Liter (g/L) Standard Deviation 0.000	-0.010 Grams per Liter (g/L) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=1 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=1 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
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 Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	-31.733 10^9 cells per Liter Standard Deviation 84.835	-280.300 10^9 cells per Liter Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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 Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	-6.133 10^9 cells per Liter Standard Deviation 33.198	-250.600 10^9 cells per Liter Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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	9.900 10^9 cells per Liter Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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 Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	-25.533 10^9 cells per Liter Standard Deviation 49.878	-158.400 10^9 cells per Liter Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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 Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	-29.733 10^9 cells per Liter Standard Deviation 36.258	-347.400 10^9 cells per Liter Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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 Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.	-36.833 10^9 cells per Liter Standard Deviation 34.662	-370.300 10^9 cells per Liter Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
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 19.00	-7.01 Micromoles per Liter (μmol/L) Standard Deviation 3.12	-15.00 Micromoles per Liter (μmol/L) Standard Deviation 2.83
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	-6.38 Micromoles per Liter (μmol/L) Standard Deviation 1.10	-13.00 Micromoles per Liter (μmol/L) Standard Deviation 4.24
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	-2.00 Micromoles per Liter (μmol/L) Standard Deviation 1.78	-8.50 Micromoles per Liter (μmol/L) Standard Deviation 7.78
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	-8.21 Micromoles per Liter (μmol/L) Standard Deviation 17.53	-14.50 Micromoles per Liter (μmol/L) Standard Deviation 10.61
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	3.65 Micromoles per Liter (μmol/L) Standard Deviation 11.83	-4.00 Micromoles per Liter (μmol/L) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.
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	17.00 Micromoles per Liter (μmol/L) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Maximum Observed Concentration (Cmax) Of Isatuximab	3.64 Micrograms per milliliter (μg/mL) Standard Deviation 1.19	7.41 Micrograms per milliliter (μg/mL) Standard Deviation 6.29	151 Micrograms per milliliter (μg/mL) Standard Deviation 121

SECONDARY outcome

Timeframe: 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.

Blood samples were collected at the specified timepoints. Tmax was defined as time to reach Cmax. The non-compartmental PK analysis was performed.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Time to Reach Cmax (Tmax) of Isatuximab	89.50 Hours (h) Interval 89.35 to 96.33	92.68 Hours (h) Interval 48.58 to 119.17	202.69 Hours (h) Interval 94.8 to 310.58

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
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 Hoursmicrograms per milliliter(hμg/mL) Geometric Coefficient of Variation 30.0	879 Hoursmicrograms per milliliter(hμg/mL) Geometric Coefficient of Variation 99.0	23900 Hoursmicrograms per milliliter(hμg/mL) Geometric Coefficient of Variation 41.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=1 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Isatuximab	560 Hoursmicrograms per milliliter(hμg/mL) Standard Deviation 171	1370 Hoursmicrograms per milliliter(hμg/mL) Standard Deviation 1350	17800 Hoursmicrograms per milliliter(hμg/mL) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.

SECONDARY outcome

Timeframe: 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.

Blood samples were collected at the specified timepoints. The non-compartmental Pharmacokinetic (PK) analysis was performed

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Mean Plasma Trough Concentration Of Isatuximab Day 15	0.0114 Micrograms per milliliter (μg/mL) Standard Deviation 0.0140	0.678 Micrograms per milliliter (μg/mL) Standard Deviation 0.994	140 Micrograms per milliliter (μg/mL) Standard Deviation 137
Part A: Mean Plasma Trough Concentration Of Isatuximab Day 29	0.167 Micrograms per milliliter (μg/mL) Standard Deviation 0.270	7.30 Micrograms per milliliter (μg/mL) Standard Deviation 7.13	134 Micrograms per milliliter (μg/mL) Standard Deviation 62.3
Part A: Mean Plasma Trough Concentration Of Isatuximab Day 43	0.00111 Micrograms per milliliter (μg/mL) Standard Deviation 0.00131	6.69 Micrograms per milliliter (μg/mL) Standard Deviation 5.90	62.0 Micrograms per milliliter (μg/mL) Standard Deviation 87.7
Part A: Mean Plasma Trough Concentration Of Isatuximab Day 57	NA Micrograms per milliliter (μg/mL) Standard Deviation NA Mean and Standard deviation could not be determined as the values were below the lower limit of quantification (LLOQ). LLOQ was 0.0005 µg/mL	10.7 Micrograms per milliliter (μg/mL) Standard Deviation 4.08	146 Micrograms per milliliter (μg/mL) Standard Deviation NA Standard deviation could not be determined when only 1 participant was analyzed.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 Participants 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 Participants Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 Participants Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.
Part A: Number Of Participants With Anti-Isatuximab Antibodies	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Blood samples were planned to be collected at the specified timepoints. Cmax was defined as maximum concentration observed after the first infusion.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Blood samples were planned to be collected at the specified timepoints.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

Adverse Events

Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B: Isatuximab up to 560 mg SC Q2W x6

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 participants at risk 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 participants at risk Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 participants at risk Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.	Part B: Isatuximab up to 560 mg SC Q2W x6 Participants were planned to receive 6 doses of Isatuximab up to 560 mg (4 mL) via SC injection Q2W through Day 71.
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • Number of events 2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Hepatobiliary disorders Liver Injury	33.3% 1/3 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Infections and infestations Sepsis	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	50.0% 1/2 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Injury, poisoning and procedural complications Infusion Related Reaction	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	50.0% 1/2 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Investigations Alanine Aminotransferase Increased	33.3% 1/3 • Number of events 2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	50.0% 1/2 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Renal and urinary disorders Acute Kidney Injury	33.3% 1/3 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.

Other adverse events

Other adverse events
Measure	Part A: Cohort 1: Isatuximab 140 mg SC Q2W x2 n=3 participants at risk 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.	Part A: Cohort 2: Isatuximab 280 mg SC Q2W x6 n=3 participants at risk Participants received 6 doses of Isatuximab 280 mg (2 mL) via SC injection Q2W through Day 71.	Part A: Cohort 3: Isatuximab 560 mg SC Q2W x6 n=2 participants at risk Participants received 6 doses of Isatuximab 560 mg (4 mL) via SC injection Q2W through Day 71.	Part B: Isatuximab up to 560 mg SC Q2W x6 Participants were planned to receive 6 doses of Isatuximab up to 560 mg (4 mL) via SC injection Q2W through Day 71.
Blood and lymphatic system disorders Splenomegaly	33.3% 1/3 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Gastrointestinal disorders Toothache	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	50.0% 1/2 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
General disorders Oedema Peripheral	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	33.3% 1/3 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	50.0% 1/2 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Infections and infestations Covid-19	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	33.3% 1/3 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Infections and infestations Urinary Tract Infection	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	50.0% 1/2 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	33.3% 1/3 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	50.0% 1/2 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.
Nervous system disorders Headache	66.7% 2/3 • Number of events 2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/3 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	0.00% 0/2 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.	— 0/0 • TEAEs were collected from first dose of study drug (Day 1) up to 30 days after last study intervention administration, approximately 101 days. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 169 days. Analysis was performed on safety 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.

Additional Information

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