FELZARTAMAB for Antibody-mediated rejection (kidney transplant) | Kidney transplant rejection

Inclusion criteria

• {"criterion_text":"- 1. At least 18 and younger than 75 years of age at the time of informed consent and is the local age of consent.\n- 10. Within 4 weeks of randomization, participants should be current on all vaccines per local country or regional public health authority (e.g., COVID-19 vaccination/boosters, pneumococcus) as determined by the Investigator.\n- 11. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test at Screening and a negative urine pregnancy test immediately prior to the first dose of study drug and they must agree to either abstain from sexual intercourse or use a highly effective method of contraception (e.g., oral or injectable hormonal contraceptives or intrauterine device) from Screening, during the study, and until 90 days after their last dose of study drug. Method of contraception must be approved by the Investigator, and monitoring and documentation in the medical record and CRF will be performed by the site. a. Female participants not of childbearing potential must not have reproductive potential, i.e., are postmenopausal (defined below) OR history of hysterectomy, OR history of bilateral salpingectomy/tubal ligation, OR history of bilateral oophorectomy. b. Females will be considered postmenopausal if no vaginal bleeding or spotting for at least 12 months and: i. If less than 55 years old, follicle stimulating hormone (FSH) must be within the laboratory’s reference range for postmenopausal females. ii. If 55 to 59 years old and there is uncertainty regarding menopausal status, FSH must be within the laboratory’s reference range for postmenopausal females. iii. If 60 years old or older, evaluation of FSH is not needed to confirm postmenopausal status.\n- 12. Male participants must agree to practice a highly effective method of birth control (e.g., abstinence from heterosexual intercourse, vasectomy, a partner who is of non-childbearing potential, or a condom with spermicide in combination with the following methods used by the female partner: hormonal birth control or intrauterine device) from Screening, during the study, and until 90 days after their last dose of study drug. Method of contraception must be approved by the Investigator, and monitoring and documentation in the medical record and CRF will be performed by the site.\n- 13. Male participants must agree not to donate sperm and females must agree not to donate ova from Screening, during the study, and for 90 days after the last dose of study drug.\n- 14. Currently on a stable standard immunosuppression regimen per local site standard of care.\n- 15. Willing and able to comply with the visits, treatments, procedures, laboratory tests, and other requirements according to the current protocol, with a high probability for compliance with and completion of the study.\n- 2. Capable of and willing to provide signed informed consent; participants must sign and date an ICF before any study-specific screening procedure is performed.\n- 3. Active or chronic active AMR (biopsy-confirmed) without TCMR per central reading, as defined by the Banff 2022 criteria\n- 4. Kidney transplant biopsy must be within 3 months (preferably within 1 month) prior to randomization. a. For participants who received any prior treatment(s) for AMR or TCMR as outlined in Exclusion Criterion 5, the kidney transplant biopsy must be performed at least 6 weeks after completing (or stopping) the prior AMR/TCMR treatment(s).\n- 5. Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors).\n- 6. Must have venous access sufficient to allow for blood sampling and IV administration of study drug as per the protocol.\n- 7. DSA: 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 single-antigen bead-based assays within 3 months prior to randomization.a. For participants who received any prior treatment(s) for AMR or TCMR as outlined in Exclusion Criterion 5, DSA must be tested at least 6 weeks after completing (or stopping) the prior AMR/TCMR treatment(s).\n- 8. eGFR: ≥25 mL/min/1.73m2 (eGFR estimated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation [KDIGO Glomerular Disease Work Group, 2021]).\n- 9. Urine protein-creatinine ratio (UPCR) <3.5 g/g."}

Exclusion criteria

• {"criterion_text":"- 1. Transplant: Blood type (ABO)-incompatible transplant.\n- 20. CD19+ B cells < 5 cells/μl or below assay-specific lower limit of quantification, whichever is greater, at Screening.\n- 21. Inadequate liver function at Screening: a. Total bilirubin > 2 × the upper limit of normal (ULN). An isolated increase in bilirubin in participants with known Gilbert’s syndrome is not a reason for exclusion. b. Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) > 2.5 × ULN.\n- 2. History of multiple organ transplants including en bloc and dual kidney transplants.\n- 22. Hypogammaglobulinemia: Serum IgG < 400 mg/dL\n- 23. Active participation in another interventional clinical study\n- 24. Any clinically significant underlying illness that, in the opinion of the Investigator, may compromise study participation, present a safety risk to the participant, or may confound the interpretation of the study results, including general non-adherence to medication therapy\n- 3. Kidney transplant biopsy demonstrating any of the following: a. TCMR classified Banff grade ≥Ia (concomitant Banff 2022 borderline TCMR cases are not an exclusion criteria). b. MVI (g+ptc)=0. c. Banff Lesion Score v (Intimal Arteritis) >0. d. De novo or recurrent thrombotic microangiopathy. e. Polyoma virus or adenovirus nephropathy. f. De novo or recurrent glomerular diseases. g. Pyelonephritis and other non-rejection induced nephropathies, e.g., obstructive nephropathies. h. Biopsy material inadequate for Central Pathology Adjudication Committee evaluation and adjudication.\n- 4. 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\n- 5. Treatment: Prior AMR/TCMR treatment (with the exception of corticosteroids) within 3 months prior to randomization is excluded as listed below. Patients 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: a. Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin [SCIg]) or PLEX. b. Complement system inhibitors (e.g., eculizumab). c. Proteasome inhibitors (e.g., bortezomib). d. Tocilizumab. e. e. Any B cell-depleting therapy (including anti-CD20 agents [e.g., rituximab]) within 3 months prior to randomization. f. Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization.\n- 6. Treatment: Prior AMR/TCMR treatment (with the exception of steroids) is excluded as listed below. Patients who received these treatments between 6 and 12 months prior to randomization must have DSA testing at least 6 weeks after completing (or stopping) treatment in order to confirm presence of HLA DSA and to determine eligibility. a. Any T cell-depleting therapy (including anti-CD52 [e.g., alemtuzumab], thymoglobulin) within 6 months prior to randomization. b. Any B cell-targeting therapy (including anti-B lymphocyte stimulator [BLyS]/B cell activating factor [BAFF], e.g., belimumab) within 6 months prior to randomization. c. Anti-interleukin (IL)-6/IL-6R agents (e.g., clazakizumab), with the exception of tocilizumab, within 6 months prior to randomization.\n- 10. Untreated active or latent tuberculosis (TB) (if not taking prophylaxis with isoniazid) based on a positive QuantiFERON-TB Gold Plus test or equivalent test, medical history, examination, and chest X-ray. a. Participants with evidence of latent TB based on QuantiFERON-TB Gold test or equivalent test without evidence of active infection (e.g., negative X-ray) should initiate treatment at least 2 weeks (or per country specific standards, whichever is longest) prior to the first dose of study drug.and then continue and complete a full course of treatment per local guidelines for latent TB. b. Participants with evidence of latent TB based on QuantiFERON-TB Gold test or equivalent test without evidence of active infection (e.g., negative X-ray) who have been previously treated for latent TB successfully and cleared by a local infectious disease physician (or physician with equivalent expertise) do not require an additional course of treatment. Documentation in the participant’s medical record is required.\n- 7. Anti-CD38 agents (e.g., daratumumab) at any time in the past.\n- 8. Belatacept maintenance immunosuppressive therapy within 3 months prior to randomization\n- 9. Women of childbearing potential: Pregnant, breastfeeding, unwilling to practice adequate contraception.\n- 12. Known history of human immunodeficiency virus (HIV) or positive HIV serological testing.\n- 13. Any active infection (viral, fungal, bacterial) precluding intensified/optimized immunosuppression.\n- 11. Active infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). Participants with positive anti-HBc (hepatitis B core antibody) will be excluded\n- 14. Active malignant disease precluding intensified immunosuppressive therapy.\n- 15. History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases; exceptions are basal cell carcinoma and squamous cell carcinoma of the skin or in situ carcinoma of the uterine cervix, if adequately treated in the opinion of the Investigator.\n- 16. Live or live-attenuatedvaccine within 4 weeks prior to Screening\n- 17. History of alcohol or illicit substance abuse, or other serious medical or psychiatric illness likely to interfere with participation in the study.\n- 18. Known hypersensitivity to felzartamab or any of its excipients (histidine, sucrose, and Tween 20).\n- 19. Inadequate hematologic function at Screening: a. Hemoglobin < 8 g/dL. b. Platelets < 100,000 cells/μL. c. White blood cell (WBC) count < 2000 cells/μL. d. Absolute neutrophil count < 1500 cells/μL."}

Primary endpoints

• {"endpoint_text":"- Percentage of participants who achieve BPHR at Week 24 (Month 6) (Banff 2022 criteria)","definition_or_measurement_approach":"Assessed at Week 24 (Month 6) using Banff 2022 criteria (as stated)."}

Secondary endpoints

• {"endpoint_text":"- Part A: • MVI score at Week 24 (Month 6) (Banff 2022 criteria) • Percentage of participants who achieve an MVI score of 0 at Week 24 (Banff 2022 criteria) • Change in dd-cfDNA from Baseline to Week 24 • Change in biopsy-based transcript composite score for AMR/MVI from Baseline to Week 24 • Change in eGFR from Baseline to Week 24","definition_or_measurement_approach":"Part A endpoints measured at Week 24 using Banff 2022 criteria for MVI; dd-cfDNA change from Baseline to Week 24; biopsy-based transcript composite score change from Baseline to Week 24; eGFR change from Baseline to Week 24."}
• {"endpoint_text":"- Part B Arm 1: • Percentage of participants who achieve BPHR (Banff 2022 criteria) • MVI score (Banff 2022 criteria) • Percentage of participants who achieve an MVI score of 0 (Banff 2022 criteria) • Change in dd-cfDNA from Baseline • Change in biopsy-based transcript composite score for AMR/MVI from Baseline • Change in eGFR from Baseline • Time to all-cause allograft loss","definition_or_measurement_approach":"Measured using Banff 2022 criteria for BPHR and MVI; biomarker changes (dd-cfDNA, biopsy transcript composite) and eGFR change from Baseline; time-to-event analysis for all-cause allograft loss."}
• {"endpoint_text":"- Part B Arm 2: • Percentage of participants who achieve BPHR (Banff 2022 criteria) • MVI score (Banff 2022 criteria) • Percentage of participants who achieve an MVI score of 0 (Banff 2022 criteria) • Change in dd-cfDNA from Week 24 • Change in biopsy-based transcript composite score for AMR/MVI from Week 24 • Change in eGFR from Week 24 • Time to all-cause allograft loss","definition_or_measurement_approach":"Measured using Banff 2022 criteria for BPHR and MVI; changes in dd-cfDNA, biopsy transcript composite score and eGFR from Week 24; time-to-event for all-cause allograft loss."}
• {"endpoint_text":"- Parts A and B: • Incidence and severity of AEs (TEAEs, SAEs, and AESIs) • Percentage of participants with TCMR on biopsy at Week 24 and Week 52 (Banff 2022 criteria) • Laboratory assessments, vital sign measurements, and ECG","definition_or_measurement_approach":"Safety endpoints include incidence/severity of TEAEs, SAEs, AESIs; TCMR assessed on biopsy at Week 24 and Week 52 per Banff 2022; routine labs, vitals and ECG monitoring as specified in protocol."}
• {"endpoint_text":"- Parts A and B: • Felzartamab serum concentrations over time • Baseline prevalence and post-Baseline incidence of ADAs against felzartamab in serum over time","definition_or_measurement_approach":"Pharmacokinetic assessment of felzartamab serum concentrations over time; immunogenicity measured as baseline prevalence and post-baseline incidence of anti-drug antibodies (ADAs) in serum over time."}

Methods

• Patient Recruitment Website (country-specific patient recruitment websites documented: e.g., K2 patient recruitment website documents listed for Czechia, Spain, Germany, Austria).
• Pre-ICF telephone contact / Pre-ICF Tel Data Consent (documents: L2 Pre-ICF Tel Data Consent / Travel vendor Pre-ICF telephone) to screen and obtain pre-consent data.
• Patient information platform services to host participant information and facilitate recruitment (third parties with role: Advarra Inc.; Longboat Clinical Limited listed with 'Patient information platform').
• Travel vendor support to assist participant travel and logistics (Scout Clinical listed with role 'Travel vendor').
• Country-specific recruitment arrangements and materials (K1 recruitment arrangements documents present for France, Czechia, Spain, Austria, Germany).

France

Earliest CTIS Part Ii Submission Date

02-06-2025

Latest Decision Or Authorization Date

23-02-2026

Processing Time Days

266

Number Of Sites

4

Number Of Participants

12

Czechia

Earliest CTIS Part Ii Submission Date

31-10-2025

Latest Decision Or Authorization Date

23-02-2026

Processing Time Days

115

Number Of Sites

1

Number Of Participants

7

Spain

Earliest CTIS Part Ii Submission Date

16-05-2025

Latest Decision Or Authorization Date

26-02-2026

Processing Time Days

286

Number Of Sites

5

Number Of Participants

15

Austria

Earliest CTIS Part Ii Submission Date

26-05-2025

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

291

Number Of Sites

1

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

02-06-2025

Latest Decision Or Authorization Date

23-02-2026

Processing Time Days

266

Number Of Sites

4

Number Of Participants

12

Primary sponsor

Full Name

Biogen Idec Research Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Advarra Inc.

Responsibilities

Patient information platform

Name

Longboat Clinical Limited

Responsibilities

Patient information platform

Name

CTI Clinical Trial and Consulting Services Europe GmbH

Responsibilities

Codes 1,12,2,5 (as listed in sponsor duties)

Name

CTI Laboratory Services Spain S.L.

Responsibilities

Code 4 (as listed in sponsor duties)

Name

Primevigilance USA Inc.

Responsibilities

code 8

Name

Scout Clinical

Responsibilities

Travel vendor

Third parties

• {"country":"United States","full_name":"Advarra Inc.","duties_or_roles":"Patient information platform","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Primevigilance USA Inc.","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Longboat Clinical Limited","duties_or_roles":"Patient information platform","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Travel vendor","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"CTI Clinical Trial and Consulting Services Europe GmbH","duties_or_roles":"codes 1,12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"CTI Laboratory Services Spain S.L.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}