Back to resultsSafety, Pharmacokinetics, and Preliminary Efficacy of Isatuximab in Patients Awaiting Kidney Transplantation
Primary Purpose
Immune System Disorder
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Isatuximab SAR650984
Acetaminophen (paracetamol) or equivalent
Ranitidine or equivalent
Diphenhydramine or equivalent
Methylprednisolone or equivalent
Montelukast or equivalent
Sponsored by
About this trial
This is an interventional treatment trial for Immune System Disorder focused on measuring Anti-CD38 monoclonal antibody
Eligibility Criteria
Inclusion criteria :
- Diagnosis of chronic kidney disease (CKD) and active candidate on the kidney donor waitlist at the time of screening.
- Body mass index (BMI) ≤40 kg/m2.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Capable of giving signed informed consent.
For Participants in Cohort A: active candidates on the kidney waitlist with living donor.
For participants in Cohort B: active candidates on the kidney waitlist with no living donor cleared for donation.
Exclusion criteria:
- Significant cardiac dysfunction
- Known active, recurrent, or chronic infection
- Active lupus or uncontrolled diabetes
- Prior treatment with rituximab within 6 months from SAR650984 administration
- Inadequate organ and bone marrow function at screening
- Pregnant or breastfeeding women or women who intend to become pregnant during participation in the study
- Known intolerance or hypersensitivity to any component of SAR650984 or premedications
- Participants who are not suitable for participation as judged by the Investigator
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number :8400003
- Investigational Site Number :8400001
- Investigational Site Number :8400002
- Investigational Site Number :8400004
- Investigational Site Number :7240002
- Investigational Site Number :7240001
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A: Participants with cPRA >=99.90%
Cohort B: Participants with cPRA 80.00% to 99.89%
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)
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).
Number of Participants With Hematological Abnormalities
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.
Number of Participants With Renal Function Abnormalities
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).
Number of Participants With Abnormal Electrolytes Parameters
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.
Number of Participants With Abnormal Metabolism Parameters
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%.
Number of Participants With Liver Function Abnormalities
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.
Percentage of Participants With Response
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.
Secondary Outcome Measures
Pharmacokinetics (PK) Parameters: Concentration Observed at the End of First Intravenous Infusion (Ceoi) of Isatuximab
Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.
PK Parameters: Maximum Concentration Observed (Cmax) After the First Infusion of Isatuximab
Cmax was defined as the maximum concentration observed after the first administration calculated using the noncompartmental analysis after the intravenous infusion of isatuximab.
PK Parameters: Time Taken to Reach Cmax (Tmax) After the First Infusion of Isatuximab
Tmax was defined as the time to reach Cmax, calculated using the non-compartmental analysis after the intravenous infusion of isatuximab.
PK Parameters: Last Concentration Observed Above the Lower Limit of Quantification (Clast) After the First Infusion of Isatuximab
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.
PK Parameters: Time of Clast (Tlast) After First Infusion of Isatuximab
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.
PK Parameters: Trough Plasma Concentrations (Ctrough) of Isatuximab
Ctrough was the plasma concentration of isatuximab observed just before (pre-dose) treatment administration.
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
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.
Number of Participants With Anti-drug Antibodies (ADA) Against Isatuximab
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.
Duration of Response (DOR)
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.
Number of Participants Achieving Target cPRA
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.
Duration for Achieving Target cPRA
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.
Number of Participants With Anti-Human Leukocyte Antigen (HLA)-Antibody Reduction
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.
Time to First Transplant Offer
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.
Time to Transplant
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.
Number of Kidney Transplant Offers
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.
Time to First Antibody Mediated Rejection (AMR) Episode
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.
Percentage of Participants Who Experienced Any Antibody Mediated Rejection (AMR)
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.
Number of Participants With Graft Survival at 6 Months Post-Transplant
Number of participants with graft survival status as functioning at 6-months post-transplant was reported in this outcome measure.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04294459
Brief Title
Safety, Pharmacokinetics, and Preliminary Efficacy of Isatuximab in Patients Awaiting Kidney Transplantation
Official Title
A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of Isatuximab (SAR650984) in Patients Awaiting Kidney Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to non-safety reasons
Study Start Date
June 18, 2020 (Actual)
Primary Completion Date
May 2, 2022 (Actual)
Study Completion Date
May 2, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary Objectives:
Phase 1: To characterize the safety and tolerability of isatuximab in kidney transplant candidates.
Phase 2: To evaluate the efficacy of isatuximab in desensitization of participants awaiting kidney transplantation.
Secondary Objectives:
Phase 2: To characterize the safety profile of isatuximab in kidney transplant candidates.
To characterize the pharmacokinetic (PK) profile of isatuximab in kidney transplant candidates.
To evaluate the immunogenicity of isatuximab.
To assess the overall efficacy of isatuximab in desensitization of participants awaiting kidney transplantation.
Detailed Description
The study had a screening period of up to 28 days, a treatment period of up to 12 weeks, a site visit FUP of up to 26 weeks, and an extended follow-up (FUP) until study cut-off.
The study duration involved site visit per participant (i.e., screening, treatment, site visit FUP was approximately 42 weeks.
The study duration included extended FUP per participant was approximately 97.7 weeks (depending on when the participant was enrolled).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune System Disorder
Keywords
Anti-CD38 monoclonal antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A: Participants with cPRA >=99.90%
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort B: Participants with cPRA 80.00% to 99.89%
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Isatuximab SAR650984
Other Intervention Name(s)
Sarclisa
Intervention Description
Pharmaceutical form: Solution for infusion
Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Acetaminophen (paracetamol) or equivalent
Intervention Description
Pharmaceutical form: Tablets
Route of administration: Oral
Intervention Type
Drug
Intervention Name(s)
Ranitidine or equivalent
Intervention Description
Pharmaceutical form: Solution
Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Diphenhydramine or equivalent
Intervention Description
Pharmaceutical form: Solution
Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone or equivalent
Intervention Description
Pharmaceutical form: Solution
Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Montelukast or equivalent
Intervention Description
Pharmaceutical form: Tablets
Route of administration: Oral
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)
Description
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).
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Number of Participants With Hematological Abnormalities
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Number of Participants With Renal Function Abnormalities
Description
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).
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Number of Participants With Abnormal Electrolytes Parameters
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Number of Participants With Abnormal Metabolism Parameters
Description
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%.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Number of Participants With Liver Function Abnormalities
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Percentage of Participants With Response
Description
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.
Time Frame
From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) Parameters: Concentration Observed at the End of First Intravenous Infusion (Ceoi) of Isatuximab
Description
Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.
Time Frame
At End of infusion on Cycle 1 Day 1
Title
PK Parameters: Maximum Concentration Observed (Cmax) After the First Infusion of Isatuximab
Description
Cmax was defined as the maximum concentration observed after the first administration calculated using the noncompartmental analysis after the intravenous infusion of isatuximab.
Time Frame
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
Title
PK Parameters: Time Taken to Reach Cmax (Tmax) After the First Infusion of Isatuximab
Description
Tmax was defined as the time to reach Cmax, calculated using the non-compartmental analysis after the intravenous infusion of isatuximab.
Time Frame
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
Title
PK Parameters: Last Concentration Observed Above the Lower Limit of Quantification (Clast) After the First Infusion of Isatuximab
Description
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.
Time Frame
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
Title
PK Parameters: Time of Clast (Tlast) After First Infusion of Isatuximab
Description
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.
Time Frame
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
Title
PK Parameters: Trough Plasma Concentrations (Ctrough) of Isatuximab
Description
Ctrough was the plasma concentration of isatuximab observed just before (pre-dose) treatment administration.
Time Frame
Cycle 2 Day 1
Title
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
Description
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.
Time Frame
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
Title
Number of Participants With Anti-drug Antibodies (ADA) Against Isatuximab
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Duration of Response (DOR)
Description
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.
Time Frame
From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)
Title
Number of Participants Achieving Target cPRA
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Duration for Achieving Target cPRA
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Number of Participants With Anti-Human Leukocyte Antigen (HLA)-Antibody Reduction
Description
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.
Time Frame
From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)
Title
Time to First Transplant Offer
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Time to Transplant
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Number of Kidney Transplant Offers
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Time to First Antibody Mediated Rejection (AMR) Episode
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Percentage of Participants Who Experienced Any Antibody Mediated Rejection (AMR)
Description
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.
Time Frame
From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
Title
Number of Participants With Graft Survival at 6 Months Post-Transplant
Description
Number of participants with graft survival status as functioning at 6-months post-transplant was reported in this outcome measure.
Time Frame
At 6 Months post-transplant
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Diagnosis of chronic kidney disease (CKD) and active candidate on the kidney donor waitlist at the time of screening.
Body mass index (BMI) </=40 kg/m^2.
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Capable of giving signed informed consent.
For Participants in Cohort A: active candidates on the kidney waitlist with living donor.
For Participants in Cohort B: active candidates on the kidney waitlist with no living donor cleared for donation.
Exclusion criteria:
Significant cardiac dysfunction.
Known active, recurrent, or chronic infection.
Active lupus or uncontrolled diabetes.
Prior treatment with rituximab within 6 months from SAR650984 administration.
Inadequate organ and bone marrow function at screening.
Pregnant or breastfeeding women or women who intend to become pregnant during participation in the study.
Known intolerance or hypersensitivity to any component of SAR650984 or pre-medications.
Participants who were not suitable for participation as judged by the Investigator.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :8400003
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Investigational Site Number :8400001
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Investigational Site Number :8400002
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Investigational Site Number :8400004
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Investigational Site Number :7240002
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08035
Country
Spain
Facility Name
Investigational Site Number :7240001
City
Hospitalet de Llobregat
State/Province
Catalunya [Cataluña]
ZIP/Postal Code
08907
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Learn more about this trial
Safety, Pharmacokinetics, and Preliminary Efficacy of Isatuximab in Patients Awaiting Kidney Transplantation
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