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.

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).

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.

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.

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.

Safety 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 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.

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

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.

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

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.

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.

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.

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.

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.

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 at the specified timepoints. Cmax was defined as maximum concentration observed after the first infusion. The non-compartmental pharmacokinetic (PK) analysis was performed.

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. Tmax was defined as time to reach Cmax. The non-compartmental PK analysis was performed.

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.

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.

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

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.

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.

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.

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.

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).

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

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.

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.

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.

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

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.

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

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

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

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

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.

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.

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.

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.

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.