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

Sanofi

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Immune System Disorder

Treatments: Drug: Isatuximab SAR650984; Drug: Methylprednisolone or equivalent; Drug: Montelukast or equivalent; Drug: Acetaminophen (paracetamol) or equivalent; Drug: Diphenhydramine or equivalent; Drug: Ranitidine or equivalent

Study type: Interventional

Funder types: Industry

Identifiers

NCT04294459

2019-004154-28 (EudraCT Number)

U1111-1238-9716 (Other Identifier)

TED16414

Details and patient eligibility

About

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.

Full 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).

Enrollment: 23 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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23 participants in 2 patient groups

Cohort A: Participants with cPRA >=99.90%

Experimental group

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).

Treatment:

Drug: Diphenhydramine or equivalent

Drug: Ranitidine or equivalent

Drug: Acetaminophen (paracetamol) or equivalent

Drug: Montelukast or equivalent

Drug: Methylprednisolone or equivalent

Drug: Isatuximab SAR650984

Cohort B: Participants with cPRA 80.00% to 99.89%

Experimental group

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).

Treatment:

Drug: Diphenhydramine or equivalent

Drug: Ranitidine or equivalent

Drug: Acetaminophen (paracetamol) or equivalent

Drug: Montelukast or equivalent

Drug: Methylprednisolone or equivalent

Drug: Isatuximab SAR650984