Clinical trial NCT04294459: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Immune System Disorder
Keywords: Anti-CD38 monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-03-04
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Number of Participants With Hematological Abnormalities
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Number of Participants With Renal Function Abnormalities
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Number of Participants With Abnormal Electrolytes Parameters
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Number of Participants With Abnormal Metabolism Parameters
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Number of Participants With Liver Function Abnormalities
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Percentage of Participants With Response
timeFrame: From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)
Secondary outcomes:
measure: Pharmacokinetics (PK) Parameters: Concentration Observed at the End of First Intravenous Infusion (Ceoi) of Isatuximab
timeFrame: At End of infusion on Cycle 1 Day 1
measure: PK Parameters: Maximum Concentration Observed (Cmax) After the First Infusion of Isatuximab
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
measure: PK Parameters: Time Taken to Reach Cmax (Tmax) After the First Infusion of Isatuximab
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
measure: PK Parameters: Last Concentration Observed Above the Lower Limit of Quantification (Clast) After the First Infusion of Isatuximab
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
measure: PK Parameters: Time of Clast (Tlast) After First Infusion of Isatuximab
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
measure: PK Parameters: Trough Plasma Concentrations (Ctrough) of Isatuximab
timeFrame: Cycle 2 Day 1
measure: 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
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
measure: Number of Participants With Anti-drug Antibodies (ADA) Against Isatuximab
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Duration of Response (DOR)
timeFrame: From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)
measure: Number of Participants Achieving Target cPRA
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Duration for Achieving Target cPRA
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Number of Participants With Anti-Human Leukocyte Antigen (HLA)-Antibody Reduction
timeFrame: From first dose of study drug until end of follow-up period (maximum duration: up to 39.1 weeks)
measure: Time to First Transplant Offer
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Time to Transplant
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Number of Kidney Transplant Offers
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Time to First Antibody Mediated Rejection (AMR) Episode
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Percentage of Participants Who Experienced Any Antibody Mediated Rejection (AMR)
timeFrame: From first dose of study drug until study cut-off date (maximum duration: up to 97.7 weeks)
measure: Number of Participants With Graft Survival at 6 Months Post-Transplant
timeFrame: At 6 Months post-transplant
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Investigational Site Number :8400003
state: California
city: Rochester
country: United States
facility: Investigational Site Number :8400001
state: Minnesota
city: New York
country: United States
facility: Investigational Site Number :8400002
state: New York
city: Houston
country: United States
facility: Investigational Site Number :8400004
state: Texas
city: Barcelona
country: Spain
facility: Investigational Site Number :7240002
state: Barcelona [Barcelona]
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number :7240001
state: Catalunya [Cataluña]
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: