FELZARTAMAB for Late isolated microvascular inflammation in kidney transplant recipients (DSA-negative MVI)

Inclusion criteria

• {"criterion_text":"- At least 18 and younger than 75 years of age at the time of informed consent and is the local age of consent.\n- 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. Live or live-attenuated vaccines must be administrated at least 4 weeks prior to screening.\n- Women of childbearing potential (as defined in Section 11.5HCG pregnancy test at Screening and a negative urine pregnancy test immediately prior to the first dose of study drug.\n- Participants assigned male at birth and participants assigned female at birth and of childbearing potential (as defined in Section 11.5) who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Section 11.5 from Screening, during the treatment period, and through EOS. If a participant withdraws from the study early, then highly effective contraception must be used for 90 days after their last dose of study drug.\n- Male participants must agree to practice a highly effective method of birth control (as described in Section 11.5) 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- Male participants must agree not to donate spermatozoa, and female participants must agree not to donate eggs from beginning at Screening, throughout the study, and for 90 days after the last dose of study drug.\n- . Currently on a stable standard immunosuppression regimen per local site SOC. Any immunosuppression regimen modification during screening will require subject re-evaluation for eligibility.\n- 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- 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- C4d-positive or C4d-negative DSA-negative MVI (biopsy-confirmed) without TCMR per central reading, as defined by the Banff 2022 criteria (Appendix 18.1)\n- Biopsy must be within 3 months (preferably within 1 month) prior to randomization. a. For participants who received any prior treatment for AMR, MVI, or TCMR as outlined in Exclusion Criterion 6, the biopsy must be performed at least 6 weeks after completing (or stopping) prior treatment.\n- Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors).\n- Must have venous access sufficient to allow for blood sampling and IV administration of study drug as per the protocol.\n- DSA: HLA Class I and II antigen-specific DSA-negative (preformed and de novo DSA) as using single-antigen bead-based assays within 3 months prior to randomization. a. For participants who received any prior treatment for AMR, isolated MVI, or TCMR as outlined in Exclusion Criterion 6, DSA must be tested at least 6 weeks after completing (or stopping) prior treatment(s\n- eGFR:≥25mL/min/1.73m2 (eGFR calculated using the CKD-EPI creatinine equation\n- UPCR <3.5 g/g."}

Exclusion criteria

• {"criterion_text":"- Transplant: Blood type (ABO)-incompatible transplant.\n- Women of childbearing potential unwilling to practice adequate contraception, and/or who are pregnant or breastfeeding\n- Active TB as described in Section 10.2.3.\n- Active infection with HBV or HCV. Participants with positive anti-HBc and negative antiHBs will be excluded\n- Known history of HIV or positive HIV serological testing\n- Active, systemic infection that is deemed serious by the Investigator. Participants who have been treated and cleared may be eligible following consultation with medical monitor.\n- Active malignant disease precluding intensified immunosuppressive therapy.\n- 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- Live or live-attenuated vaccine within 4 weeks prior to Screening.\n- History of alcohol or illicit substance abuse, or other serious medical or psychiatric illness likely to interfere with participation in the study.\n- Known hypersensitivity to felzartamab or any of its excipients.\n- History of multiple organ transplants including en bloc and dual kidney transplants.\n- Inadequate hematologic function at Screening\n- CD19+ B cells < 5 cells/ l or below assay-specific lower limit of quantification, whichever is greater, at Screening.\n- Inadequate liver function at Screening\n- Hypogammaglobulinemia: Serum IgG < 400 mg/dL.\n- Active participation in another interventional clinical study.\n- 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- Presence of HLA donor-specific antibodies\n- Biopsy demonstrating any of the following: a. not an exclusion criterion). b. MVI (g+ptc)<1. 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, such as obstructive nephropathies. h. Biopsy material inadequate for Central Pathology Adjudication Committee evaluation\n- Acute, rapid decline in renal function, defined as a participant likely to require renal replacement therapy within the next 30 days as determined by the Investigator\n- Prior AMR or 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 DSA-negative MVI and to determine eligibility: a. Intravenous or subcutaneous immunoglobulin (IVIg or SCIg) or PLEX. b. Complement system inhibitors (e.g., eculizumab). c. Proteasome inhibitors (e.g., bortezomib). d. Tocilizumab. e. Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization.\n- Prior AMR or 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 absence of HLA DSA and to determine eligibility. a. Any B cell-depleting therapy (including anti-CD20 agents [e.g., rituximab]) within 6 months prior to randomization. b. Any T cell-depleting therapy (including anti-CD52 [e.g., alemtuzumab], thymoglobulin) within 6 months prior to randomization. c. Any B cell-targeting therapy (including anti-BLyS/BAFF, e.g., belimumab) within 6 months prior to randomization. d. Anti-IL-6/IL-6R agents (e.g., clazakizumab), with the exception of tocilizumab, within 6 months prior to randomization.\n- Anti-CD38 agents (e.g., daratumumab) at any time in the past.\n- Belatacept maintenance immunosuppressive therapy within 3 months prior to randomization"}

Primary endpoints

• {"endpoint_text":"- Percentage of participants who achieve BPHR at Week 24 (Month 6) (Banff 2022 criteria)","definition_or_measurement_approach":"BPHR assessed by biopsy at Week 24 according to Banff 2022 criteria (histological resolution as defined by Banff 2022)."}

Secondary endpoints

• {"endpoint_text":"- Part A : • MVI score at Week 24 (Month 6) (Banff 2022 criteria) • Percentage of participants who achieve MVI score of 0 at Week 24 (Banff 2022 criteria) • Change in eGFR from Baseline to Week 24 • Percentage of participants in the C4d-positive cohort who achieve BPHR at Week 24 (Month 6) (Banff 2022 criteria)","definition_or_measurement_approach":"MVI score and MVI=0 assessed by biopsy using Banff 2022 criteria; eGFR change measured from Baseline to Week 24 (eGFR method described elsewhere in protocol). C4d-positive cohort analysis per Banff 2022-defined BPHR at 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 the MVI score of 0 (Banff 2022 criteria) • Change in estimated glomerular filtration rate (eGFR) from Baseline • Time to all-cause allograft loss","definition_or_measurement_approach":"Endpoints assessed by biopsy per Banff 2022 criteria for BPHR and MVI; 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 MVI score of 0 (Banff 2022 criteria) • Change in eGFR from Week 24 • Time to all-cause allograft loss","definition_or_measurement_approach":"Endpoints assessed by biopsy per Banff 2022 criteria for BPHR and MVI; eGFR change measured from Week 24; time-to-event analysis for all-cause allograft loss."}
• {"endpoint_text":"- Parts A and B: • Incidence and severity of adverse events (AEs) [treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)] • Percentage of participants with TCMR on biopsy at Week 24 and at Week 52 (Banff 2022 criteria) • Laboratory assessments, vital sign measurements, and ECG","definition_or_measurement_approach":"Safety endpoints collected as standard AE reporting (TEAEs, SAEs, AESIs); TCMR assessed by biopsy at Week 24 and Week 52 per Banff 2022 criteria; routine labs, vital signs and ECG per protocol schedule."}

Methods

• Country-specific recruitment arrangements documents available (Recruitment arrangements files for Austria, France, Germany, Spain, Czechia).
• Email communications to potential participants (Scout/other vendor materials: 'Other subject information material_Email Comm').
• Telephone contact and telephone consent procedures ('Other subject information material_Telephone Consent').
• Study brochure / site brochures (Scout Study Brochure and Other subject information material_Scout_Study Brochure).
• Reloadable ScoutPass mailer (digital/mail-based outreach) referenced in country materials (Germany list).
• Travel assistance vendor support to participants (Scout Clinical listed as travel vendor).

Austria

Earliest CTIS Part Ii Submission Date

04-02-2026

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

5

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

12-12-2025

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

66

Number Of Sites

4

Number Of Participants

8

Germany

Earliest CTIS Part Ii Submission Date

25-11-2025

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

77

Number Of Sites

4

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

15-01-2026

Latest Decision Or Authorization Date

12-02-2026

Processing Time Days

28

Number Of Sites

5

Number Of Participants

10

Czechia

Earliest CTIS Part Ii Submission Date

08-01-2026

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

33

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Biogen Idec Research Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

CTI Clinical Trial and Consulting Services Europe GmbH

Responsibilities

sponsorDuties codes: 1,12,2,5; contact regulatoryeurope@ctifacts.com; phone +4973140008412

Name

CTI Laboratory Services Spain S.L.

Responsibilities

sponsorDuties code: 4; laboratory services; contact nleal@ctifacts.com; phone +34944045504

Third parties

• {"country":"Spain","full_name":"CTI Laboratory Services Spain S.L.","duties_or_roles":"sponsorDuties codes: 4; contact nleal@ctifacts.com; phone +34944045504","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"CTI Clinical Trial and Consulting Services Europe GmbH","duties_or_roles":"sponsorDuties codes: 1, 12, 2, 5; contact regulatoryeurope@ctifacts.com; phone +4973140008412","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"sponsorDuties code: 15 (Travel vendor); contact clientcompliance@scoutclinical.com; phone +19725036119","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Primevigilance USA Inc.","duties_or_roles":"sponsorDuties code: 8 (pharmacovigilance); contact india.romero@primevigilance.com; phone 9199499959","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties code: 15 (IRT and eCOA); contact support@suvoda.com; phone +18557886321","organisation_type":"Non-Pharmaceutical company"}