Felzartamab in Late Antibody-Mediated Rejection

NCT05021484 | Completed Phase 2 DMC

• 2 other identifiers: EK1161/20212021-000545-40
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 2

Brief Summary

This prospective trial will assess the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics and efficacy of the fully human CD38 monoclonal antibody felzartamab in kidney transplant recipients with late active or chronic-active ABMR. The study is designed as a randomized, controlled, double-blind pilot phase 2 trial. Participants will be randomized to receive either felzartamab or placebo for a period of six months, and then followed for another six months. After six and twelve months, study participants will be subjected to follow-up allograft biopsies.

Conditions

Antibody-mediated Rejection

Keywords

CD38; Kidney transplantation

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events

  (Serious) adverse events will be classified using the Medical Dictionary for Regulatory Activities (MedDRA). Documentation of an AE will include the assessment of its relationship with the study drug (unrelated, related) and the severity of AE will be graded on a three-point scale (mild, moderate, severe).

  12 months

Secondary Outcomes (17)

• Felzartamab serum concentration

  At day 0, week 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 44, 48 and 52

• Anti-Felzartamab antibodies

  At day 0, week 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 44, 48 and 52

• Morphologic ABMR categories

  At week 24 and at week 52

• Serum donor-specific antibody (DSA) levels

  Week 0, 12, 24, and 52

• Serum immunoglobulin levels

  Week 0, 12, 24, and 52

Study Arms (2)

Felzartamab

ACTIVE COMPARATOR

9 doses of felzartamab as an intravenous infusion over 6 treatment cycles at 28 days each. Dosing occurs every week in cycle 1 and every four weeks in cycles 2-6.

Drug: Felzartamab

Placebo

PLACEBO COMPARATOR

9 doses of placebo as an intravenous infusion over 6 treatment cycles at 28 days each. Dosing occurs every week in cycle 1 and every four weeks in cycles 2-6.

Drug: Placebo

Interventions

Felzartamab DRUG

Intravenous infusion in regular intervals over 6 months

Also known as: MOR202, CD38 monoclonal antibody

Felzartamab

Placebo DRUG

Intravenous infusion in regular intervals over 6 months

Also known as: 0.9% Saline

Placebo

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written informed consent
• Age \>18 years (maximum: 80 years)
• Functioning living or deceased donor allograft after ≥180 days post-transplantation
• eGFR ≥20 ml/min/1.73 m2 (CKD-EPI formula)
• HLA class I and/or II antigen-specific antibodies (preformed and/or de novo DSA).
• Active or chronic/active ABMR (±C4d in PTC) according to the Banff 2019 classification
• Molecular ABMR score (MMDx) ≥0.2

You may not qualify if:

• Patients actively participating in another clinical trial
• Age ≤18 years
• Female subject is pregnant or lactating or not on adequate contraceptive therapy
• ABO-incompatible transplant
• Index biopsy results:
• T-cell-mediated rejection classified Banff grade ≥I
• De novo or recurrent severe thrombotic microangiopathy
• Polyoma virus nephropathy
• De novo or recurrent glomerulonephritis
• Acute rejection treatment ≤3 month before screening
• Previous treatment with other CD38 monoclonal antibodies (e.g. daratumumab)
• Previous treatment with other immunomodulatory monoclonal/polyclonal antibodies (e.g. CD20 Ab rituximab, IL-6/IL-6R Ab) ≤3 months before study treatment
• Total bilirubin \>2×the upper limit of normal \[ULN\], alanine transaminase and aspartate aminotransferase \>2·5×ULN
• Haemoglobin \<8 g/dL
• Thrombocytopenia: Platelets \<100 G/L

Sponsors & Collaborators

• Farsad Eskandary: lead
• Charite University, Berlin, Germany: collaborator
• University of Alberta: collaborator
• Biogen: collaborator

Study Sites (2)

Medical University of Vienna

Vienna, 1090, Austria

Location

Charité University

Berlin, 10117, Germany

Location

Related Publications (6)

• Doberer K, Klager J, Gualdoni GA, Mayer KA, Eskandary F, Farkash EA, Agis H, Reiter T, Reindl-Schwaighofer R, Wahrmann M, Cohen G, Haslacher H, Bond G, Simonitsch-Klupp I, Halloran PF, Bohmig GA. CD38 Antibody Daratumumab for the Treatment of Chronic Active Antibody-mediated Kidney Allograft Rejection. Transplantation. 2021 Feb 1;105(2):451-457. doi: 10.1097/TP.0000000000003247.

  PMID: 32235256 BACKGROUND

• Raab MS, Engelhardt M, Blank A, Goldschmidt H, Agis H, Blau IW, Einsele H, Ferstl B, Schub N, Rollig C, Weisel K, Winderlich M, Griese J, Hartle S, Weirather J, Jarutat T, Peschel C, Chatterjee M. MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1-2a trial. Lancet Haematol. 2020 May;7(5):e381-e394. doi: 10.1016/S2352-3026(19)30249-2. Epub 2020 Mar 11.

  PMID: 32171061 BACKGROUND

• Mayer KA, Doberer K, Eskandary F, Halloran PF, Bohmig GA. New concepts in chronic antibody-mediated kidney allograft rejection: prevention and treatment. Curr Opin Organ Transplant. 2021 Feb 1;26(1):97-105. doi: 10.1097/MOT.0000000000000832.

  PMID: 33315763 BACKGROUND

• Madill-Thomsen KS, Gauthier PT, Abouljoud M, Bhati C, Bruno D, Ciszek M, Durlik M, Feng S, Foroncewicz B, Grat M, Jurczyk K, Levitsky J, McCaughan G, Maluf D, Montano-Loza A, Moonka D, Mucha K, Myslak M, Perkowska-Ptasinska A, Piecha G, Reichman T, Tronina O, Wawrzynowicz-Syczewska M, Zeair S, Halloran PF. Defining an NK Cell-enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study. Transplantation. 2025 Aug 1;109(8):1367-1382. doi: 10.1097/TP.0000000000005269. Epub 2025 Jan 9.

  PMID: 39780312 DERIVED

• Mayer KA, Schrezenmeier E, Diebold M, Halloran PF, Schatzl M, Schranz S, Haindl S, Kasbohm S, Kainz A, Eskandary F, Doberer K, Patel UD, Dudani JS, Regele H, Kozakowski N, Klager J, Boxhammer R, Amann K, Puchhammer-Stockl E, Vietzen H, Beck J, Schutz E, Akifova A, Firbas C, Gilbert HN, Osmanodja B, Halleck F, Jilma B, Budde K, Bohmig GA. A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection. N Engl J Med. 2024 Jul 11;391(2):122-132. doi: 10.1056/NEJMoa2400763. Epub 2024 May 25.

  PMID: 38804514 DERIVED

• Mayer KA, Budde K, Halloran PF, Doberer K, Rostaing L, Eskandary F, Christamentl A, Wahrmann M, Regele H, Schranz S, Ely S, Firbas C, Schorgenhofer C, Kainz A, Loupy A, Hartle S, Boxhammer R, Jilma B, Bohmig GA. Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol for a phase 2 trial. Trials. 2022 Apr 8;23(1):270. doi: 10.1186/s13063-022-06198-9.

  PMID: 35395951 DERIVED

MeSH Terms

Interventions

felzartamab; Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Georg A Böhmig, MD

  Department of Internal Medicine III, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Ass. Prof. Dr.

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 25, 2021
• Study Start: October 6, 2021
• Primary Completion: March 7, 2024
• Study Completion: March 7, 2024
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); DE (1)