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

Chronic Kidney Disease (CKD) Clinical Trial

Official title:

A Dose Escalation and Proof-of-Concept Study of REGN5459 or REGN5458 (BCMA × CD3 Bispecific Antibodies) for Desensitization of Chronic Kidney Disease Patients in Need of Kidney Transplantation Who Are Highly Sensitized to Human Leukocyte Antigen

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05092347
• Other study ID #: R5459-RT-1944
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 2, 2022
• Est. completion date: October 21, 2025

Study information

• Verified date: August 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 21, 2025
• Est. primary completion date: October 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease (CKD)
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• REGN5459
Administered by intravenous (IV) infusion
• REGN5458
Administered by intravenous (IV) infusion

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Northwestern University Comprehensive Transplant Center	Chicago	Illinois
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Yale University School of Medicine Transplant Surgery	New Haven	Connecticut
United States	New York University Langone Health - Transplant Institute	New York	New York
United States	University of California, Irvine	Orange	California
United States	University of Pennsylvania-Penn Transplant Institute	Philadelphia	Pennsylvania
United States	University of California at San Francisco (UCSF) Connie Frank Transplant Center at UCSF	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse event(s) of interest (AEI) from the first dose through end of the safety observation period		Up to approximately 4 weeks
Primary	Incidence and severity of treatment-emergent adverse events (TEAE)s from the first study drug dose up to the end of the study	TEAEs include adverse events of special interest (AESI) and serious adverse events (SAEs)	Up to 30 weeks
Secondary	Proportion of Participants with a clinically meaningful reduction in anti-HLA alloantibodies	Clinically meaningful reduction in anti-HLA alloantibodies are defined as either: Reduction in Calculated panel-reactive antibody (cPRA) from baseline, or; Reduction in the peak (immunodominant) anti-HLA mean fluorescence intensity (MFI) to <5,000, or by =50% by Single antigen bead (SAB) assay	Up to 30 weeks
Secondary	Maximum reduction in the peak (immunodominant) MFI of anti-HLA alloantibodies from baseline		Up to 30 weeks
Secondary	Percent change from baseline in the peak (immunodominant) MFI		Up to 30 weeks
Secondary	Percent change from baseline in the sum of MFI of anti-HLA alloantibodies using the SAB assay		Up to 30 weeks
Secondary	Time to first clinically meaningful reduction in anti-HLA alloantibody levels by SAB assay	Defined as peak anti-HLA alloantibody MFI <5,000 or =50% reduction	Up to 30 weeks
Secondary	Time to maximal reduction in anti-HLA alloantibody levels by SAB assay	Defined as peak anti-HLA alloantibody MFI <5,000 or =50% reduction	Up to 30 weeks
Secondary	Maximum reduction in cPRA from baseline		Up to 30 weeks
Secondary	Time to first clinically meaningful reduction in cPRA		Up to 30 weeks
Secondary	Time to maximal reduction in cPRA from baseline		Up to 30 weeks
Secondary	Duration of a reduction in peak anti-HLA alloantibody to MFI <5,000 or by =50% by SAB assay		Up to 30 weeks
Secondary	Duration of maximal reduction in anti-HLA alloantibody MFI by SAB assay		Up to 30 weeks
Secondary	Duration of maximal reduction in cPRA by SAB assay		Up to 30 weeks
Secondary	Serum concentration of Immunoglobulin(Ig) classes over time		Up to 30 weeks
Secondary	Percent change from baseline of serum concentration of Ig classes		Up to 30 weeks
Secondary	Concentration of REGN5458 in serum over time		Up to 30 weeks
Secondary	Concentration of REGN5459 in serum over time		Up to 30 weeks
Secondary	Incidence of treatment-emergent REGN5458 anti-drug antibodies (ADA) over time		Up to 30 weeks
Secondary	Incidence of treatment-emergent REGN5459 ADA over time		Up to 30 weeks