Clinical trial NCT05092347: 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)
Official title: A Dose Escalation and Proof-of-Concept Study of Vonsetamig (BCMA × CD3 Bispecific Antibody) for Desensitization of Chronic Kidney Disease Patients in Need of Kidney Transplantation Who Are Highly Sensitized to Human Leukocyte Antigen
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Kidney Disease (CKD)
Keywords: Kidney Transplant
Hemodialysis
Desensitization
Human Leukocyte Antigen (HLA)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-10-25
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility 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 / exclusion criteria apply

Primary outcomes:
measure: Incidence of adverse event(s) of interest (AEI) from the first dose through end of the safety observation period
timeFrame: Up to approximately 6 weeks
measure: Incidence and severity of treatment-emergent adverse events (TEAE)s from the first study drug dose up to the end of the study
timeFrame: Up to 78 weeks
Secondary outcomes:
measure: Proportion of Participants with a clinically meaningful reduction in anti-HLA alloantibodies
timeFrame: Up to 78 weeks
measure: Maximum reduction in the peak (immunodominant) MFI of anti-HLA alloantibodies from baseline
timeFrame: Up to 78 weeks
measure: Percent change from baseline in the peak (immunodominant) MFI
timeFrame: Up to 78 weeks
measure: Percent change from baseline in the sum of MFI of anti-HLA alloantibodies using the SAB assay
timeFrame: Up to 78 weeks
measure: Time to first clinically meaningful reduction in anti-HLA alloantibody levels by SAB assay
timeFrame: Up to 78 weeks
measure: Time to maximal reduction in anti-HLA alloantibody levels by SAB assay
timeFrame: Up to 78 weeks
measure: Maximum reduction in cPRA from baseline
timeFrame: Up to 78 weeks
measure: Time to first clinically meaningful reduction in cPRA
timeFrame: Up to 78 weeks
measure: Time to maximal reduction in cPRA from baseline
timeFrame: Up to 78 weeks
measure: Duration of a reduction in peak anti-HLA alloantibody to MFI <5,000 or by ≥50% by SAB assay
timeFrame: Up to 78 weeks
measure: Duration of maximal reduction in anti-HLA alloantibody MFI by SAB assay
timeFrame: Up to 78 weeks
measure: Duration of maximal reduction in cPRA by SAB assay
timeFrame: Up to 78 weeks
measure: Serum concentration of Immunoglobulin (Ig) classes over time
timeFrame: Up to 78 weeks
measure: Percent change from baseline of serum concentration of Ig classes
timeFrame: Up to 78 weeks
measure: Concentration of vonsetamig in serum over time
timeFrame: Up to 78 weeks
measure: Incidence of treatment-emergent anti-drug antibodies (ADAs) to vonsetamig over time
timeFrame: Up to 78 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: San Francisco
country: United States
facility: Connie Frank Transplant Center at UCSF
state: California
city: New Haven
country: United States
facility: Yale University of Medicine
state: Connecticut
city: Washington
country: United States
facility: Medstar Georgetown Transplant Institute - 2-PHC
state: District of Columbia
city: Chicago
country: United States
facility: Comprehensive Transplant Center
state: Illinois
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: Philadelphia
country: United States
facility: Penn Transplant Institute
state: Pennsylvania
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: