A Double-Blind, Placebo-Controlled, Multicenter, Randomized Phase 2 Trial Evaluating the Efficacy and Safety of Felzartamab in Recipients of Kidney Transplants with Late Isolated Microvascular Inflammation (MVI)- (299AR201-TRANSPIRE)
Date de révision : 22/04/2026
8 participants
Homme Femme
A partir de 18 ans
Critères :
Critères d'inclusion :
- At least 18 and younger than 75 years of age at the time of informed consent and is the local age of consent.
- 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.
- 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.
- 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.
- 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.
- 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.
- . Currently on a stable standard immunosuppression regimen per local site SOC. Any immunosuppression regimen modification during screening will require subject re-evaluation for eligibility.
- 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.
- Capable of and willing to provide signed informed consent; participants must sign and date an ICF before any study-specific screening procedure is performed.
- 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)
- 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.
- Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors).
- Must have venous access sufficient to allow for blood sampling and IV administration of study drug as per the protocol.
- 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
- eGFR:≥25mL/min/1.73m2 (eGFR calculated using the CKD-EPI creatinine equation
- UPCR <3.5 g/g.
Critères d'exclusion :
- Transplant: Blood type (ABO)-incompatible transplant.
- Women of childbearing potential unwilling to practice adequate contraception, and/or who are pregnant or breastfeeding
- Active TB as described in Section 10.2.3.
- Active infection with HBV or HCV. Participants with positive anti-HBc and negative antiHBs will be excluded
- Known history of HIV or positive HIV serological testing
- 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.
- Active malignant disease precluding intensified immunosuppressive therapy.
- 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.
- Live or live-attenuated vaccine within 4 weeks prior to Screening.
- History of alcohol or illicit substance abuse, or other serious medical or psychiatric illness likely to interfere with participation in the study.
- Known hypersensitivity to felzartamab or any of its excipients.
- History of multiple organ transplants including en bloc and dual kidney transplants.
- Inadequate hematologic function at Screening
- CD19+ B cells < 5 cells/ l or below assay-specific lower limit of quantification, whichever is greater, at Screening.
- Inadequate liver function at Screening
- Hypogammaglobulinemia: Serum IgG < 400 mg/dL.
- Active participation in another interventional clinical study.
- 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.
- Presence of HLA donor-specific antibodies
- 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
- 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
- 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.
- 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.
- Anti-CD38 agents (e.g., daratumumab) at any time in the past.
- Belatacept maintenance immunosuppressive therapy within 3 months prior to randomization
Lieux et contacts
Informations pratiques pour participer à cet essai.
Contacts
Sites des essais
Adresse
Centre Hospitalier Universitaire De Toulouse
31059 Toulouse Cedex 9 France
Centre Hospitalier Universitaire De Bordeaux
33000 Bordeaux France
Centre Hospitalier Universitaire Grenoble Alpes
38043 Grenoble Cedex 9 France
Comment postuler ?
Pour participer à cet essai clinique, veuillez contacter la personne responsable de l'étude. Vous trouverez ses coordonnées dans la section "Lieux et contacts", puis "Contacts".