A Study to Learn How Safe and Tolerable Vonsetamig is in Adult Patients With Chronic Kidney Disease (CKD) Who Need Kidney Transplantation and Are Highly Sensitized to Human Leukocyte Antigen (HLA)
- Registration Number
- NCT05092347
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The purpose of this study is to determine whether vonsetamig will safely decrease anti-HLA antibodies to allow for kidney transplantation.
Vonsetamig is being studied for treatment of patients in need of kidney transplantation who are highly sensitized to HLA.
The study is looking at several other research questions, including:
* Side effects that may be experienced from taking vonsetamig
* How vonsetamig works in the body
* How much vonsetamig is present in the blood
* If vonsetamig works to lower levels of antibodies to HLA
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 56
- 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, as defined in the protocol
- Adequate hematologic and adequate hepatic function as defined in the protocol
- Willing and able to comply with clinic visits and study-related procedures
Key
- Current or active malignancy not in remission for at least 1 year
- Central nervous system (CNS) pathology or history of CNS neurodegenerative or movement disorders
- Patients who have had their spleen removed, including patients with functional asplenia
- Patients who have received a stem cell transplantation within 5 years
- Use of investigational agents within 8 weeks or 5 half-lives of study drug administration (whichever is larger)
- Total plasma IgG <300 mg/dL at screening
- 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
- Received a calcineurin inhibitor (eg, tacrolimus, cyclosporine) within 30 days of study drug administration
- Received cyclophosphamide, rituximab, obinutuzumab, other anti-CD20 or B cell-depleting agents, or proteasome inhibitors or anti-CD38 therapies (eg, isatuximab, daratumumab) within 12 months of study drug administration
- Prior treatment with any anti-BCMA antibody (including antibody drug conjugate or bsAb) or BCMA-directed CAR-T cell therapy, as described in the protocol
- Has received a COVID-19 vaccination, as described in the protocol
Note: Other protocol defined inclusion / exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Vonsetamig Vonsetamig -
- Primary Outcome Measures
Name Time Method Incidence of adverse event(s) of interest (AEI) from the first dose through end of the safety observation period Up to approximately 6 weeks Incidence and severity of treatment-emergent adverse events (TEAE)s from the first study drug dose up to the end of the study Up to 78 weeks TEAEs include adverse events of special interest (AESI) and serious adverse events (SAEs)
- Secondary Outcome Measures
Name Time Method Percent change from baseline in the peak (immunodominant) MFI Up to 78 weeks Time to first clinically meaningful reduction in anti-HLA alloantibody levels by SAB assay Up to 78 weeks Defined as peak anti-HLA alloantibody MFI \<5,000 or ≥50% reduction
Duration of maximal reduction in anti-HLA alloantibody MFI by SAB assay Up to 78 weeks Time to maximal reduction in cPRA from baseline Up to 78 weeks Percent change from baseline in the sum of MFI of anti-HLA alloantibodies using the SAB assay Up to 78 weeks Maximum reduction in cPRA from baseline Up to 78 weeks Duration of a reduction in peak anti-HLA alloantibody to MFI <5,000 or by ≥50% by SAB assay Up to 78 weeks Duration of maximal reduction in cPRA by SAB assay Up to 78 weeks Serum concentration of Immunoglobulin (Ig) classes over time Up to 78 weeks Percent change from baseline of serum concentration of Ig classes Up to 78 weeks Concentration of vonsetamig in serum over time Up to 78 weeks Incidence of treatment-emergent anti-drug antibodies (ADAs) to vonsetamig over time Up to 78 weeks Proportion of Participants with a clinically meaningful reduction in anti-HLA alloantibodies Up to 78 weeks 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) assayMaximum reduction in the peak (immunodominant) MFI of anti-HLA alloantibodies from baseline Up to 78 weeks Time to maximal reduction in anti-HLA alloantibody levels by SAB assay Up to 78 weeks Defined as peak anti-HLA alloantibody MFI \<5,000 or ≥50% reduction
Time to first clinically meaningful reduction in cPRA Up to 78 weeks
Trial Locations
- Locations (10)
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California Irvine
🇺🇸Orange, California, United States
Connie Frank Transplant Center at UCSF
🇺🇸San Francisco, California, United States
Yale University of Medicine
🇺🇸New Haven, Connecticut, United States
Medstar Georgetown Transplant Institute - 2-PHC
🇺🇸Washington, District of Columbia, United States
Comprehensive Transplant Center
🇺🇸Chicago, Illinois, United States
John Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
New York University Langone Health
🇺🇸New York, New York, United States
Penn Transplant Institute
🇺🇸Philadelphia, Pennsylvania, United States