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

NCT ID: NCT04294459

Last Updated: 2025-09-17

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-18

Study Completion Date

2022-05-02

Brief Summary

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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

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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).

Conditions

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Immune System Disorder

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

Isatuximab SAR650984

Intervention Type DRUG

Pharmaceutical form: Solution for infusion

Route of administration: Intravenous

Acetaminophen (paracetamol) or equivalent

Intervention Type DRUG

Pharmaceutical form: Tablets

Route of administration: Oral

Ranitidine or equivalent

Intervention Type DRUG

Pharmaceutical form: Solution

Route of administration: Intravenous

Diphenhydramine or equivalent

Intervention Type DRUG

Pharmaceutical form: Solution

Route of administration: Intravenous

Methylprednisolone or equivalent

Intervention Type DRUG

Pharmaceutical form: Solution

Route of administration: Intravenous

Montelukast or equivalent

Intervention Type DRUG

Pharmaceutical form: Tablets

Route of administration: Oral

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).

Group Type EXPERIMENTAL

Isatuximab SAR650984

Intervention Type DRUG

Pharmaceutical form: Solution for infusion

Route of administration: Intravenous

Acetaminophen (paracetamol) or equivalent

Intervention Type DRUG

Pharmaceutical form: Tablets

Route of administration: Oral

Ranitidine or equivalent

Intervention Type DRUG

Pharmaceutical form: Solution

Route of administration: Intravenous

Diphenhydramine or equivalent

Intervention Type DRUG

Pharmaceutical form: Solution

Route of administration: Intravenous

Methylprednisolone or equivalent

Intervention Type DRUG

Pharmaceutical form: Solution

Route of administration: Intravenous

Montelukast or equivalent

Intervention Type DRUG

Pharmaceutical form: Tablets

Route of administration: Oral

Interventions

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Isatuximab SAR650984

Pharmaceutical form: Solution for infusion

Route of administration: Intravenous

Intervention Type DRUG

Acetaminophen (paracetamol) or equivalent

Pharmaceutical form: Tablets

Route of administration: Oral

Intervention Type DRUG

Ranitidine or equivalent

Pharmaceutical form: Solution

Route of administration: Intravenous

Intervention Type DRUG

Diphenhydramine or equivalent

Pharmaceutical form: Solution

Route of administration: Intravenous

Intervention Type DRUG

Methylprednisolone or equivalent

Pharmaceutical form: Solution

Route of administration: Intravenous

Intervention Type DRUG

Montelukast or equivalent

Pharmaceutical form: Tablets

Route of administration: Oral

Intervention Type DRUG

Other Intervention Names

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Sarclisa

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number :8400003

San Francisco, California, United States

Site Status

Investigational Site Number :8400001

Rochester, Minnesota, United States

Site Status

Investigational Site Number :8400002

New York, New York, United States

Site Status

Investigational Site Number :8400004

Houston, Texas, United States

Site Status

Investigational Site Number :7240002

Barcelona, Barcelona [Barcelona], Spain

Site Status

Investigational Site Number :7240001

L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain

Site Status

Countries

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United States Spain

References

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Mannon RB, Vincenti FG. Poised for Innovation: Considerations for End Points for New Drug Development in Kidney Transplantation. J Am Soc Nephrol. 2024 Nov 1;35(11):1603-1606. doi: 10.1681/ASN.0000000000000475. Epub 2024 Aug 5. No abstract available.

Reference Type DERIVED
PMID: 39102302 (View on PubMed)

Vincenti F, Bestard O, Brar A, Cruzado JM, Seron D, Gaber AO, Ali N, Tambur AR, Lee H, Abbadessa G, Paul JA, Dudek M, Siegel RJ, Torija A, Semiond D, Lepine L, Ternes N, Montgomery RA, Stegall M. Isatuximab Monotherapy for Desensitization in Highly Sensitized Patients Awaiting Kidney Transplant. J Am Soc Nephrol. 2024 Mar 1;35(3):347-360. doi: 10.1681/ASN.0000000000000287. Epub 2023 Dec 26.

Reference Type DERIVED
PMID: 38147137 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2019-004154-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1238-9716

Identifier Type: OTHER

Identifier Source: secondary_id

TED16414

Identifier Type: -

Identifier Source: org_study_id

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