Clinical trial NCT06685757: A Trial of Felzartamab in Kidney Transplant Recipients With Late Antibody-Mediated Rejection (AMR)
Official title: A Double-Blind, Placebo-Controlled, Multicenter, Randomized Phase 3 Trial Evaluating the Efficacy and Safety of Felzartamab in Kidney Transplant Recipients With Late Antibody-Mediated Rejection (AMR)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Antibody-mediated Rejection
Keywords: AMR
Felzartamab
Kidney Transplant
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2024-11-12
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main goal of this trial is to evaluate the efficacy of felzartamab compared to placebo in kidney transplant recipients diagnosed with late active or chronic active AMR.

Detailed description: NOTE: Biogen is the Sponsor of study 299AR301.

Eligibility criteria: Key Inclusion Criteria:

* Active or chronic active AMR (biopsy-confirmed) without TCMR per central reading, as defined by the Banff 2022 criteria.
* Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors).
* Donor-specific antibody (DSA): Human leukocyte antigen (HLA) Class I and/or II antigen-specific DSA-positive (preformed and/or de novo DSA) as determined by the local laboratory's definition of positivity using singleantigen bead-based assays within 3 months prior to randomization.

Key Exclusion Criteria:

* Transplant: Blood type (ABO)-incompatible transplant.
* History of multiple organ transplants including en bloc and dual kidney transplants.
* Acute, rapid decline in renal function, defined as a participant likely to require renal replacement therapy within the subsequent 30 days as determined by the Investigator.
* Treatment: Prior AMR/TCMR treatment (with the exception of corticosteroids) within 3 months prior to randomization is excluded as listed below. Participants who received any of these treatments between 3 and 6 months prior to randomization must have both a renal biopsy (IC3) and DSA testing at least 6 weeks after completing (or stopping) treatment in order to confirm continuing AMR and to determine eligibility:

  1. Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or PLEX.
  2. Complement system inhibitors (e.g., eculizumab).
  3. Proteasome inhibitors (e.g., bortezomib).
  4. Tocilizumab. e. Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization.

Other protocol-defined inclusion/exclusion criteria apply.

Primary outcomes:
measure: Part A: Percentage of Participants Who Achieve Biopsy-proven Histologic Resolution (BPHR)
timeFrame: Week 24
Secondary outcomes:
measure: Part A: Microvascular Inflammation (MVI) Score
timeFrame: Week 24
measure: Part A: Percentage of Participants Who Achieve an MVI Score of 0
timeFrame: Week 24
measure: Part A: Change from Baseline in Donor-derived Cell-free DNA (dd-cfDNA)
timeFrame: Baseline, Week 24
measure: Part A: Change from Baseline in Biopsy-based Transcript Composite Score for AMR/MVI
timeFrame: Baseline, Week 24
measure: Part A: Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline, Week 24
measure: Part B: Percentage of Participants Who Achieve BPHR
timeFrame: Weeks 24 and 52
measure: Part B: MVI Score
timeFrame: Weeks 24 and 52
measure: Part B: Percentage of Participants Who Achieve an MVI Score of 0
timeFrame: Weeks 24 and 52
measure: Part B: Change from Baseline in dd-cfDNA
timeFrame: Baseline, Weeks 24 and 52
measure: Part B: Change from Baseline in Biopsy-based Transcript Composite Score for AMR/MVI
timeFrame: Baseline, Weeks 24 and 52
measure: Part B: Change from Baseline in eGFR
timeFrame: Baseline, Weeks 24 and 52
measure: Part B: Time to All-cause Allograft Loss
timeFrame: Up to Week 52
measure: Parts A and B: Number of Participants with Adverse Events
timeFrame: From time of first dose to end of trial visit (Up to Week 52)
measure: Parts A and B: Number of Participants with Clinically Significant Laboratory Abnormalities
timeFrame: From time of first dose to end of trial visit (Up to Week 52)
measure: Parts A and B: Number of Participants with Clinically Significant Vital Signs Abnormalities
timeFrame: From time of first dose to end of trial visit (Up to Week 52)
measure: Parts A and B: Number of Participants with Clinically Significant ECG Abnormalities
timeFrame: From time of first dose to end of trial visit (Up to Week 52)
measure: Parts A and B: Percentage of Participants with T Cell-mediated Rejection (TCMR) by Biopsy
timeFrame: Weeks 24 and 52
measure: Parts A and B: Felzartamab Serum Concentration
timeFrame: Up to Week 52
measure: Parts A and B: Number of Participants with Anti-drug Antibodies (ADAs) against Felzartamab
timeFrame: Baseline, up to Week 52
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Orange
country: United States
facility: Providence Healthcare
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: West Orange
country: United States
facility: Cooperman Barnabas Medical Center
state: New Jersey
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine - Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: