Trial Outcomes & Findings for Safety, Pharmacokinetics, and Preliminary Efficacy of Isatuximab in Patients Awaiting Kidney Transplantation (NCT NCT04294459)

Last Updated: 2025-09-17

Results Overview

An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious adverse events (SAEs) were 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 or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (defined as the time from the first dose of study drug until study cut-off date).

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

23 participants

Primary outcome timeframe

From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Results posted on

2025-09-17

Participant Flow

Study was conducted at 6 active sites in 2 countries. A total of 23 participants were enrolled between 18 Jun 2020 and 02 Nov 2021 and received isatuximab monotherapy.

Study was planned to be conducted in 2 parts: Phase 1 (safety run-in) and Phase 2 (efficacy). Sponsor decided to terminate the study for non-safety reasons on 02 May 2022. Based on available clinical data at time of interim analysis, it was determined that enrollment of remaining participants was unlikely to have any significant impact on study results and hence trial was stopped. Participant flow, baseline, outcome measures and safety data were presented for combined Phase 1 and 2 population.

Participant milestones

Participant milestones
Measure	Cohort A: Participants With cPRA >=99.90% Participants with calculated panel reactive antibodies (cPRA) \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 milligrams per kilogram (mg/kg), intravenous (IV) infusion, once weekly (QW) for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then every 2 weeks (Q2W) for subsequent treatment cycles (each cycle of 28 days) until unacceptable adverse events (AEs) or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Overall Study STARTED	12	11
Overall Study COMPLETED	12	10
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Participants With cPRA >=99.90% Participants with calculated panel reactive antibodies (cPRA) \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 milligrams per kilogram (mg/kg), intravenous (IV) infusion, once weekly (QW) for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then every 2 weeks (Q2W) for subsequent treatment cycles (each cycle of 28 days) until unacceptable adverse events (AEs) or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Overall Study Adverse Event	0	1

Baseline Characteristics

Safety, Pharmacokinetics, and Preliminary Efficacy of Isatuximab in Patients Awaiting Kidney Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90%; (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Total n=23 Participants Total of all reporting groups
Age, Continuous	49.7 years STANDARD_DEVIATION 11.9 • n=93 Participants	48.2 years STANDARD_DEVIATION 12.3 • n=4 Participants	49.0 years STANDARD_DEVIATION 11.8 • n=27 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	2 Participants n=4 Participants	8 Participants n=27 Participants
Sex: Female, Male Male	6 Participants n=93 Participants	9 Participants n=4 Participants	15 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) White	4 Participants n=93 Participants	9 Participants n=4 Participants	13 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on all treated population which included all participants who received at least one dose of isatuximab. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	3 Participants	4 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on all treated population. Here, "number analyzed" = participants with available data for each specified category. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Abnormal hematological parameters assessed were anemia, platelet count decreased, neutrophil count decreased, lymphocyte count decreased and monocytes. The hematological abnormality grades were based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Monocytes were assessed as per potentially clinically significant abnormality (PCSA) criteria defined as: greater than (\>) 0.7\*10\^9/L.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Hematological Abnormalities Anemia: Grade 1	6 Participants	8 Participants
Number of Participants With Hematological Abnormalities Anemia: Grade 4	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Platelet count decreased: Grade 1	2 Participants	6 Participants
Number of Participants With Hematological Abnormalities Platelet count decreased: Grade 4	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Neutrophil count decreased: Grade 1	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Neutrophil count decreased: Grade 2	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Lymphocyte count decreased: Grade 2	1 Participants	1 Participants
Number of Participants With Hematological Abnormalities Lymphocyte count decreased: Grade 3	1 Participants	0 Participants
Number of Participants With Hematological Abnormalities Anemia: Grade 2	3 Participants	2 Participants
Number of Participants With Hematological Abnormalities Anemia: Grade 3	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Platelet count decreased: Grade 2	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Platelet count decreased: Grade 3	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Neutrophil count decreased: Grade 3	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Neutrophil count decreased: Grade 4	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Lymphocyte count decreased: Grade 1	4 Participants	2 Participants
Number of Participants With Hematological Abnormalities Lymphocyte count decreased: Grade 4	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Monocytes (PCSA) > 0.7*10^9/L	3 Participants	3 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on all treated population. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Abnormal renal parameters assessed were creatinine increased and estimated Glomerular Filtration Rate (eGFR). The renal function abnormality grades were based on NCI-CTCAE, Version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. eGFR was assessed as per PCSA criteria: 60 (less than equal to) \<= to less than (\<) 90 milliliter/minute/1.73 meter square (mL/min/1.73m\^2) (Mild), 30\<= to \<60 mL/min/1.73m\^2 (Moderate), 15\<=to \<30 mL/min/1.73m\^2 (Severe), \<15 mL/min/1.73m\^2 (End Stage Renal Disease).

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Renal Function Abnormalities Creatinine increased: Grade 1	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities eGFR: 60<= - <90 mL/min/1.73m^2	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities eGFR: <15 mL/min/1.73m^2	12 Participants	11 Participants
Number of Participants With Renal Function Abnormalities Creatinine increased: Grade 2	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities Creatinine increased: Grade 3	1 Participants	3 Participants
Number of Participants With Renal Function Abnormalities Creatinine increased: Grade 4	11 Participants	8 Participants
Number of Participants With Renal Function Abnormalities eGFR: 30<= - <60 mL/min/1.73m^2	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities eGFR: 15<= - <30 mL/min/1.73m^2	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on all treated population. Here, 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field signifies that none of the participants were available for assessment of the specified parameter. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Abnormal electrolyte parameters assessed were hypernatremia, hyponatremia, hyperkalemia, hypokalemia, hypercalcemia, hypocalcemia, blood bicarbonate decreased, hypermagnesemia, hypomagnesemia and chloride. The abnormal grades were based on NCI-CTCAE, Version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Chloride was estimated as per PCSA criteria: \<80 millimoles per liter (mmol/L) and \>115 mmol/L.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Abnormal Electrolytes Parameters Hypernatremia: Grade 1	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hyponatremia: Grade 2	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hyponatremia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hyponatremia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hyperkalemia: Grade 1	2 Participants	6 Participants
Number of Participants With Abnormal Electrolytes Parameters Hyperkalemia: Grade 2	3 Participants	1 Participants
Number of Participants With Abnormal Electrolytes Parameters Hyperkalemia: Grade 3	1 Participants	2 Participants
Number of Participants With Abnormal Electrolytes Parameters Hyperkalemia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypokalemia: Grade 1	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypercalcemia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypocalcemia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypermagnesemia: Grade 1	2 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypermagnesemia: Grade 2	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypermagnesemia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypomagnesemia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypernatremia: Grade 2	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypernatremia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypernatremia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hyponatremia: Grade 1	4 Participants	1 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypokalemia: Grade 2	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypokalemia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypokalemia: Grade 4	1 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypercalcemia: Grade 1	0 Participants	1 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypercalcemia: Grade 2	1 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypercalcemia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypocalcemia: Grade 1	6 Participants	5 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypocalcemia: Grade 2	0 Participants	2 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypocalcemia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypermagnesemia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypomagnesemia: Grade 1	3 Participants	3 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypomagnesemia: Grade 2	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Hypomagnesemia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Chloride (PCSA): <80 mmol/L	0 Participants	0 Participants
Number of Participants With Abnormal Electrolytes Parameters Chloride (PCSA): >115 mmol/L	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on all treated population. Here, "number analyzed" = participants with available data for each specified category and "0" in the number analyzed field signifies that none of the participants were available for assessment of the specified parameter. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Abnormal metabolism parameters assessed were hypoglycemia, hypoalbuminemia and glycated Hemoglobin (HbA1c). The abnormal grades were based on NCI-CTCAE, Version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. HbA1c was estimated as per PCSA criteria: \>8%.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Abnormal Metabolism Parameters Hypoglycemia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Metabolism Parameters Hypoglycemia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Metabolism Parameters Hypoalbuminemia: Grade 2	2 Participants	2 Participants
Number of Participants With Abnormal Metabolism Parameters Hypoalbuminemia: Grade 3	0 Participants	0 Participants
Number of Participants With Abnormal Metabolism Parameters Hypoalbuminemia: Grade 4	0 Participants	0 Participants
Number of Participants With Abnormal Metabolism Parameters Hypoalbuminemia: Grade 1	3 Participants	0 Participants
Number of Participants With Abnormal Metabolism Parameters Hypoglycemia: Grade 1	1 Participants	2 Participants
Number of Participants With Abnormal Metabolism Parameters Hypoglycemia: Grade 2	1 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on all treated population. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Abnormal liver function parameters assessed were Alanine aminotransferase (ALT) increased, Aspartate aminotransferase (AST) increased, Alkaline phosphatase (ALP) increased, and Total bilirubin (TB) increased. The abnormal grades were based on NCI-CTCAE, Version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Liver Function Abnormalities ALT increased: Grade 1	1 Participants	1 Participants
Number of Participants With Liver Function Abnormalities TB increased: Grade 1	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities TB increased: Grade 2	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities ALT increased: Grade 3	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities ALT increased: Grade 4	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities AST increased: Grade 1	1 Participants	0 Participants
Number of Participants With Liver Function Abnormalities AST increased: Grade 2	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities ALT increased: Grade 2	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities AST increased: Grade 3	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities AST increased: Grade 4	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities ALP increased: Grade 1	3 Participants	2 Participants
Number of Participants With Liver Function Abnormalities ALP increased: Grade 2	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities ALP increased: Grade 3	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities ALP increased: Grade 4	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities TB increased: Grade 3	0 Participants	0 Participants
Number of Participants With Liver Function Abnormalities TB increased: Grade 4	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)

Population: Analysis was performed on efficacy evaluable population which included all participants who received at least 1 dose of isatuximab, with an evaluable Baseline and at least 1 evaluable post-baseline efficacy assessment and received \>=75% of planned cumulative doses. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Response was defined as the percentage of participants meeting at least one of the predefined desensitization efficacy criteria as measured by single antigen bead (SAB) assay as follows: reduction in cPRA resulting in at least 100% increase of likelihood of finding a compatible donor; reduction in antibody titer (\>=75% reduction from Baseline) to achieve target cPRA; elimination of \>=1 human leukocyte antigen (HLA) antibody (i.e., mean fluorescence intensity \[MFI\] reduced to \<2000) as measured by a SAB assay, for antibodies with Baseline MFI \>=3000.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Percentage of Participants With Response	83.3 percentage of participants Interval 51.6 to 97.9	81.8 percentage of participants Interval 48.2 to 97.7

SECONDARY outcome

Timeframe: At End of infusion on Cycle 1 Day 1

Population: Analysis was performed on pharmacokinetic (PK) population which included all participants who receive at least 1 dose of isatuximab, with at least 1 available concentration result post treatment. Here, "overall number of participants analyzed" signifies participants with available data for this outcome measure. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=11 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Pharmacokinetics (PK) Parameters: Concentration Observed at the End of First Intravenous Infusion (Ceoi) of Isatuximab	290 micrograms per milliliter (mcg/mL) Standard Deviation 128	270 micrograms per milliliter (mcg/mL) Standard Deviation 101

SECONDARY outcome

Timeframe: At Start of infusion (SOI), End of infusion (EOI), EOI+4H (initial protocol) EOI+1H (amended protocol), 72H and 168H on Day 1 of Cycle 1

Population: Analysis was performed on PK population. Here, "overall number of participants analyzed" signifies participants with available data for this outcome measure. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Cmax was defined as the maximum concentration observed after the first administration calculated using the noncompartmental analysis after the intravenous infusion of isatuximab.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=11 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
PK Parameters: Maximum Concentration Observed (Cmax) After the First Infusion of Isatuximab	295 mcg/mL Standard Deviation 128	285 mcg/mL Standard Deviation 94.0

SECONDARY outcome

Timeframe: At Start of infusion (SOI), End of infusion (EOI), EOI+4H (initial protocol) EOI+1H (amended protocol), 72H and 168H on Day 1 of Cycle 1

Tmax was defined as the time to reach Cmax, calculated using the non-compartmental analysis after the intravenous infusion of isatuximab.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=11 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
PK Parameters: Time Taken to Reach Cmax (Tmax) After the First Infusion of Isatuximab	3.67 hours Interval 2.0 to 6.03	3.40 hours Interval 2.25 to 4.63

SECONDARY outcome

Timeframe: At Start of infusion (SOI), End of infusion (EOI), EOI+4H (initial protocol) EOI+1H (amended protocol), 72H and 168H on Day 1 of Cycle 1

Clast was defined as the last concentration of isatuximab observed above the lower limit of quantification calculated using non-compartmental analysis after the first infusion of isatuximab.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=11 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
PK Parameters: Last Concentration Observed Above the Lower Limit of Quantification (Clast) After the First Infusion of Isatuximab	104 mcg/mL Standard Deviation 41.7	76.3 mcg/mL Standard Deviation 21.3

SECONDARY outcome

Timeframe: At Start of infusion (SOI), End of infusion (EOI), EOI+4H (initial protocol) EOI+1H (amended protocol), 72H and 168H on Day 1 of Cycle 1

Tlast was defined as the time of last concentration observed above the lower limit of quantification, calculated using the non-compartmental analysis after the intravenous infusion of isatuximab.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=11 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
PK Parameters: Time of Clast (Tlast) After First Infusion of Isatuximab	166.00 hours Interval 49.6 to 169.0	167.00 hours Interval 78.8 to 168.0

SECONDARY outcome

Timeframe: Cycle 2 Day 1

Ctrough was the plasma concentration of isatuximab observed just before (pre-dose) treatment administration.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=11 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=10 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
PK Parameters: Trough Plasma Concentrations (Ctrough) of Isatuximab	308 mcg/mL Standard Deviation 79.4	246 mcg/mL Standard Deviation 60.6

SECONDARY outcome

Timeframe: At Start of infusion (SOI), End of infusion (EOI), EOI+4H (initial protocol) EOI+1H (amended protocol), 72H and 168H on Day 1 of Cycle 1

AUC0-168 hours was defined as the area under the plasma concentration versus time curve from time 0 to 168 hours post dose calculated using trapezoidal method after first infusion of isatuximab.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=10 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=10 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
PK Parameters: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 168 Hours Over the Dosing Interval (AUC0-168 Hours) After First Infusion of Isatuximab	29400 microgramshours/milliliter (mcgh/mL) Standard Deviation 7400	20000 microgramshours/milliliter (mcgh/mL) Standard Deviation 5240

SECONDARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on anti-drug antibodies (ADA) population which included all participants who receive at least 1 dose of isatuximab, with at least 1 available ADA result post-treatment. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

ADA responses were categorized as treatment boosted ADA and treatment-induced ADA. Treatment boosted ADA was defined as pre-existing ADAs with a significant increase in the ADA titer during the study compared to the Baseline titer. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without pre-existing ADA.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Anti-drug Antibodies (ADA) Against Isatuximab Treatment-induced ADA	0 Participants	0 Participants
Number of Participants With Anti-drug Antibodies (ADA) Against Isatuximab Treatment boosted ADA	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)

Population: Analysis was performed on responder population which included all participants who received at least 1 dose of isatuximab, with an evaluable Baseline and at least 1 evaluable post-baseline efficacy assessment and received \>=75% of planned cumulative doses. Here, "overall number of participants analyzed" signifies participants with available data for this outcome measure. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Duration of response (DOR) was defined as time (in weeks) from laboratory sample collection date used in determining a participant to be a responder (defined as participants meeting at least one of the predefined desensitization efficacy criteria: reduction in cPRA resulting in at least 100% increase of likelihood of finding a compatible donor; reduction in antibody titer \[\>=75% reduction from Baseline\] to achieve target cPRA; elimination of \>=1 anti-HLA antibody i.e. MFI reduced to \<2000 as measured by a SAB assay, for antibodies with Baseline MFI \>=3000) up to the laboratory sample collection date when participant was confirmed as no longer meeting any response criterion (i.e., non-responder) or the date of death due to any cause, whichever occurs first. DOR was analyzed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=10 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=9 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Duration of Response (DOR)	NA weeks Interval 4.857 to Due to insufficient number of participants with events, median DOR and upper limit of confidence interval (CI) was not reached.	NA weeks Interval 4.143 to Due to insufficient number of participants with events, median DOR and upper limit of CI was not reached.

SECONDARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on efficacy evaluable population. Here, "overall number of participants analyzed" signifies participants with available data for this outcome measure. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Target calculated panel reactive antibodies (cPRA) was defined as the reduction of cPRA required to achieve at least 100% increase of likelihood of compatible donor (LCD). Number of participants who achieved target cPRA was assessed using the Organ Procurement and Transplantation Network (OPTN) calculator during the specified timepoint were reported in this outcome measure. Participants who retained their target cPRA values were censored at the date of the last available laboratory assessment achieving their target cPRA.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=7 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=6 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants Achieving Target cPRA	4 Participants	2 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Duration of achieving target cPRA was defined as the time (in weeks) from laboratory sample collection date of achieving target cPRA (defined as the reduction of cPRA required to achieve at least 100% increase of LCD) the first time up to the laboratory sample collection date when no longer achieving target cPRA calculated using OPTN calculator or the date of death due to any cause, whichever occurs first. The duration of achieving target cPRA was assessed using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=4 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=2 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Duration for Achieving Target cPRA	NA weeks Interval 3.429 to Due to insufficient number of participants with events, median and upper limit of CI was not reached.	7.29 weeks Due to insufficient number of participants with events, upper and lower limit of CI was not reached.

SECONDARY outcome

Timeframe: From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)

Population: Analysis was performed on efficacy evaluable population. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Number of participants with anti-HLA-antibody (Baseline MFI \>=3000) reduced to \<2000 as measured using a SAB assay per central laboratory assessment was reported in this outcome measure. Participants were categorized in various categories of number of antibodies which were reduced as: none, 1-5, \>5-10, \>10-15, and \>15. If multiple visits had the same number of total anti-HLA antibody reduction, the last visit data was summarized.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Anti-Human Leukocyte Antigen (HLA)-Antibody Reduction None	2 Participants	2 Participants
Number of Participants With Anti-Human Leukocyte Antigen (HLA)-Antibody Reduction 1-5 antibodies	4 Participants	4 Participants
Number of Participants With Anti-Human Leukocyte Antigen (HLA)-Antibody Reduction >5-10 antibodies	4 Participants	4 Participants
Number of Participants With Anti-Human Leukocyte Antigen (HLA)-Antibody Reduction >10-15 antibodies	1 Participants	0 Participants
Number of Participants With Anti-Human Leukocyte Antigen (HLA)-Antibody Reduction >15 antibodies	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on efficacy-evaluable population. Here, "overall number of participants analyzed" signifies participants with available data for this outcome measure. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Time to first transplant offer was defined as time (in days) from date of first study treatment dose up to date of first kidney transplant offer. Data on transplant status were collected and followed up until study cut-off date.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=3 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=3 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Time to First Transplant Offer	373 days Interval 248.0 to 517.0	156 days Interval 117.0 to 402.0

SECONDARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on efficacy evaluable population. Here, "overall number of participants analyzed" signifies participants with available data for this outcome measure and included only participants who accepted transplant offer. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Time to transplant was defined as time (in days) from date of first study treatment dose up to date of kidney transplant. Data on transplant status were collected and followed up until study cut-off date.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=2 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=2 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Time to Transplant	445 days Interval 373.0 to 517.0	259.5 days Interval 117.0 to 402.0

SECONDARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Analysis was performed on efficacy-evaluable population. Data was planned to be collected and analyzed for the combined Phase 1 and 2 population.

Number of kidney transplants offers received for each participant was reported in the outcome measure. Data on transplant offers were collected and followed up until study cut-off date.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=12 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Kidney Transplant Offers	3 transplant offers	3 transplant offers

SECONDARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Data for this outcome measure was not collected and analyzed as no participants experienced a kidney transplant graft loss due to an AMR episode as of study terminated date.

Time to first AMR was defined as time from date of first study treatment dose up to date of biopsy with first AMR (defined as the graft rejection due to generation of antibodies against the graft). Transplanted participants without any AMR were censored at the participant's last assessment or contact date collected in the study or at the analysis cut-off date, whichever was earlier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)

Population: Data for this outcome measure was not collected and analyzed as no participants experienced a kidney transplant graft loss due to an AMR episode, as of study terminated date.

Antibody mediated rejection was defined as the graft rejection due to generation of antibodies against the graft. The number of participants with AMR field checked as 'yes' based on the graft rejection biopsy in the electronic case report form was considered.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 6 Months post-transplant

Population: Analysis was performed on efficacy evaluable population. Here, "overall number of participants analyzed" signifies participants with evaluable data for this outcome measure.

Number of participants with graft survival status as functioning at 6-months post-transplant was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort A: Participants With cPRA >=99.90% n=1 Participants Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=1 Participants Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Number of Participants With Graft Survival at 6 Months Post-Transplant	1 Participants	0 Participants

Adverse Events

Cohort A: Participants With cPRA >=99.90%

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Cohort B: Participants With cPRA 80.00% to 99.89%

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cohort A: Participants With cPRA >=99.90% n=12 participants at risk Participants with cPRA \>=99.90% (indicating active candidates on kidney transplant waitlist) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).	Cohort B: Participants With cPRA 80.00% to 99.89% n=11 participants at risk Participants with cPRA between 80.00% to 99.89% (indicating active candidates on kidney transplant waitlist with no living donor cleared for donation) received isatuximab 10 mg/kg, IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1) and then Q2W for subsequent treatment cycles (each cycle of 28 days) until unacceptable AEs or participant's decision to stop the treatment (maximum treatment duration: 13 weeks).
Infections and infestations Covid-19	0.00% 0/12 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	9.1% 1/11 • Number of events 1 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
Infections and infestations Nasopharyngitis	8.3% 1/12 • Number of events 1 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	0.00% 0/11 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
Nervous system disorders Headache	8.3% 1/12 • Number of events 1 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	0.00% 0/11 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
Cardiac disorders Tachycardia	8.3% 1/12 • Number of events 1 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	0.00% 0/11 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	8.3% 1/12 • Number of events 1 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	0.00% 0/11 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
Gastrointestinal disorders Nausea	8.3% 1/12 • Number of events 1 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	0.00% 0/11 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Number of events 2 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	0.00% 0/11 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
Musculoskeletal and connective tissue disorders Temporomandibular Joint Syndrome	8.3% 1/12 • Number of events 1 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	0.00% 0/11 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
General disorders Chills	8.3% 1/12 • Number of events 1 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	0.00% 0/11 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.
Injury, poisoning and procedural complications Infusion Related Reaction	16.7% 2/12 • Number of events 3 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.	27.3% 3/11 • Number of events 3 • From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks) Analysis was performed on all treated population.

Additional Information

Trial Transparency Team

Sanofi Aventis Recherche & Développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
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