A Trial of Felzartamab in Kidney Transplant Recipients With Late Antibody-Mediated Rejection (AMR)

Phase 3

Recruiting

• Conditions: Antibody-mediated Rejection
• Interventions: Drug: Felzartamab; Drug: Placebo

• Registration Number: NCT06685757
• Lead Sponsor: Biogen

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.

Study Timeline

• Study First Submitted: 2024-11-11
• Study First Submitted QC: 2024-11-11
• Study First Posted: 2024-11-12
• Study Start: 2024-12-03
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-05
• Last Update Posted: 2025-05-06
• Primary Completion: 2026-12-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Felzartamab	Felzartamab	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Part A: Percentage of Participants Who Achieve Biopsy-proven Histologic Resolution (BPHR)	Week 24

Secondary Outcome Measures

Name	Time	Method
Parts A and B: Percentage of Participants with T Cell-mediated Rejection (TCMR) by Biopsy	Weeks 24 and 52
Parts A and B: Felzartamab Serum Concentration	Up to Week 52
Parts A and B: Number of Participants with Anti-drug Antibodies (ADAs) against Felzartamab	Baseline, up to Week 52
Part A: Microvascular Inflammation (MVI) Score	Week 24
Part A: Percentage of Participants Who Achieve an MVI Score of 0	Week 24
Part A: Change from Baseline in Donor-derived Cell-free DNA (dd-cfDNA)	Baseline, Week 24
Part A: Change from Baseline in Biopsy-based Transcript Composite Score for AMR/MVI	Baseline, Week 24
Part A: Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)	Baseline, Week 24
Part B: Percentage of Participants Who Achieve BPHR	Weeks 24 and 52
Part B: MVI Score	Weeks 24 and 52
Part B: Percentage of Participants Who Achieve an MVI Score of 0	Weeks 24 and 52
Part B: Change from Baseline in dd-cfDNA	Baseline, Weeks 24 and 52
Part B: Change from Baseline in Biopsy-based Transcript Composite Score for AMR/MVI	Baseline, Weeks 24 and 52
Part B: Change from Baseline in eGFR	Baseline, Weeks 24 and 52
Part B: Time to All-cause Allograft Loss	Up to Week 52
Parts A and B: Number of Participants with Adverse Events	From time of first dose to end of trial visit (Up to Week 52)
Parts A and B: Number of Participants with Clinically Significant Laboratory Abnormalities	From time of first dose to end of trial visit (Up to Week 52)
Parts A and B: Number of Participants with Clinically Significant Vital Signs Abnormalities	From time of first dose to end of trial visit (Up to Week 52)
Parts A and B: Number of Participants with Clinically Significant ECG Abnormalities	From time of first dose to end of trial visit (Up to Week 52)

Trial Locations

Locations (14)

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

UCLA; 🇺🇸 Los Angeles, California, United States

Providence Healthcare; 🇺🇸 Orange, California, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

University of Nebraska; 🇺🇸 Omaha, Nebraska, United States

Cooperman Barnabas Medical Center; 🇺🇸 West Orange, New Jersey, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Penn Medicine - Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Biogen West Investigational Site; 🇺🇸 Nashville, Tennessee, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States