Chronic Kidney Disease (CKD)
Conditions
Keywords
Kidney Transplant, Hemodialysis, Desensitization, Human Leukocyte Antigen (HLA)
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
Interventions
DRUGVonsetamig
Administered by intravenous (IV) infusion
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion 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, as defined in the protocol 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. 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 12 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, as described in the protocol 11. Has received a COVID-19 vaccination, as described in the protocol Note: Other protocol defined inclusion /
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) assay |
| Maximum reduction in the peak (immunodominant) MFI of anti-HLA alloantibodies from baseline | Up to 78 weeks | — |
| Percent change from baseline in the peak (immunodominant) MFI | 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 | — |
| 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 |
| 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 |
| Maximum reduction in cPRA from baseline | Up to 78 weeks | — |
| Time to first clinically meaningful reduction in cPRA | Up to 78 weeks | — |
| Time to maximal 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 anti-HLA alloantibody MFI 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 | — |
Countries
United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed