Study for Desensitization of Chronic Kidney Disease in Adult Patients in Need of a Kidney Transplant Who Are Highly Sensitized to Human Leukocyte Antigen

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Chronic Kidney Disease (CKD)

Treatments: Drug: REGN5458; Drug: REGN5459

Study type: Interventional

Funder types: Industry

Identifiers

NCT05092347

R5459-RT-1944

Details and patient eligibility

About

The primary objective of the study is to assess the safety and tolerability of REGN5459 (Part A) or REGN5458 (Part B) as monotherapy in patients with chronic kidney disease (CKD) who need kidney transplantation and are highly sensitized to human leukocyte antigen (HLA).

The secondary objectives of the study are to determine/assess the following for REGN5459 (Part A) or REGN5458 (Part B):

• Dose regimen(s) that result in a clinically meaningful reduction of anti-HLA alloantibody levels
• Effect on calculated panel-reactive antibody (cPRA) levels
• Time to maximal and clinically meaningful reduction in anti-HLA alloantibody levels
• Duration of the effect of study drug on the reduction of anti-HLA alloantibodies
• Effect on circulating immunoglobulin (Ig) classes (isotypes)
• Pharmacokinetics (PK) properties
• Immunogenicity

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Has Chronic Kidney Disease (CKD) requiring hemodialysis, and awaiting kidney transplant on the United Network for Organ Sharing (UNOS), with a cPRA ≥99.9%, or those with a cPRA >98% (98.1% to 99.8%) who have spent 5 years or longer on the waitlist
2. Adequate hematologic and adequate hepatic function as defined in the protocol
3. Willing and able to comply with clinic visits and study-related procedures

Key Exclusion Criteria:

1. Current or active malignancy not in remission for at least 1 year
2. Central nervous system (CNS) pathology or history of CNS neurodegenerative or movement disorders
3. Patients who have had their spleen removed, including patients with functional asplenia
4. Patients who have received a stem cell transplantation within 5 years
5. Use of investigational agents within 8 weeks or 5 half-lives of study drug administration (whichever is larger)
6. Hypogammaglobulinemia, defined as total plasma IgG <300 mg/dL at screening
7. Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone (or anti-inflammatory equivalent) within 72 hours of start of study drug administration
8. Received a calcineurin inhibitor (eg, tacrolimus, cyclosporine) within 30 days of study drug administration
9. Received cyclophosphamide, rituximab, obinutuzumab, other anti-CD20 or B cell-depleting agents, or proteasome inhibitors or anti-CD38 therapies (eg, isatuximab, daratumumab) within 6 months of study drug administration
10. Prior treatment with any anti-BCMA antibody (including antibody drug conjugate or bsAb) or BCMA-directed CAR-T cell therapy
11. Has received a COVID-19 vaccination within 1 week of planned start of study drug, or for which the planned COVID-19 vaccination would not be completed 1 week before start of study drug

Note: Other protocol defined inclusion / exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

REGN5459

Experimental group

Description:

REGN5459 escalating dose

Treatment:

Drug: REGN5459

REGN5458

Experimental group

Description:

REGN5458 escalating dose

Treatment:

Drug: REGN5458