A Study of Felzartamab in Kidney Transplant Recipients with Late Antibody-Mediated Rejection (AMR)
Zusammenfassung der Studie
In clinical research, better treatment options are being sought for kidney transplant recipients who experience late antibody-mediated rejection (AMR). A kidney transplant is a medical procedure for people with long-term kidney failure. In this procedure, a healthy kidney is removed from a person (the donor) and implanted into another person with kidney failure (the recipient). Sometimes kidney transplants can fail because the recipient develops antibodies against the donor kidney. Antibodies are proteins of the immune system that fight substances not recognized by the body. These antibodies can lead to rejection of the kidney, meaning it does not function properly in the body. Rejection can occur soon after the transplantation procedure. However, in late AMR, this happens more than 6 months later. This is due to inflammation over time and the body producing specific antibodies against the transplanted kidney, known as donor-specific antibodies (DSA). Currently, there are no standard treatments to prevent late AMR. There are certain treatment options, but these do not work well for all affected individuals, especially when rejection occurs months after transplantation. Therefore, there is an unmet, urgent medical need for people with late AMR.
(BASEC)
Untersuchte Intervention
Participants with active AMR or chronically active AMR, whose kidney transplantation was at least 6 months ago, will be included in the study 299AR301. The study consists of 2 parts; Part A is randomized, meaning participants will receive either the investigational drug Felzartamab or the corresponding placebo (a dummy drug without active substance) in a 2:1 ratio randomly. This also means that neither the participant nor the investigator will know which of these groups the participant has been assigned to (Felzartamab or placebo). Part B is open-label (i.e., all participants receive Felzartamab). The administered dose of Felzartamab is based on body weight, as described in the dosing and administration section.
• In Part A (6 months), participants will receive either 9 doses of Felzartamab (Arm 1) or the corresponding placebo (Arm 2) in a 2:1 ratio randomly.
For Part A:
o Participants assigned to Arm 1 will receive treatment with 9 doses of Felzartamab, administered intravenously in weeks 0, 1, 2, 3, 4, 8, 12, 16, and 20.
o Participants assigned to Arm 2 will receive corresponding doses of placebo (dummy drug).
• In Part B, all participants will receive Felzartamab.
o Participants in Arm 1 will receive 3 intravenous doses of Felzartamab in weeks 28, 36, and 44, and
o participants in Arm 2 will receive 9 intravenous doses of Felzartamab in weeks 24, 25, 26, 27, 28, 32, 36, 40, and 44.
A histological evaluation of the kidney transplant based on a tissue sample, as well as an assessment of certain genetic information from it, will be conducted for participants in both Arms 1 and 2 before the first administration of the investigational drug, in week 24 and week 52. The overall study design is presented in the main part of the study protocol, section 5. After completion of this study, participants (from both arms) may be offered participation in a separate open-label extension study with continued Felzartamab treatment.
(BASEC)
Untersuchte Krankheit(en)
late antibody-mediated rejection (AMR) in kidney transplant recipients
(BASEC)
1. Age of at least 18 and less than 75 years at the time of informed consent 2. Able and willing to sign the informed consent; participants must sign and date an information and consent form before undergoing study-specific screening procedures. 3. Active or chronically active AMR (antibody-mediated rejection), confirmed by biopsy, without TCMR (rejection by specific immune cells (T-cells) according to central findings, as defined by the Banff 2022 criteria (The Banff classification is an international standard used to assess the histological changes in the transplanted kidney). (BASEC)
Ausschlusskriterien
1. Transplant: Blood group-incompatible transplant. 2. Multiple organ transplants in medical history, including transplantation of both kidneys along with major blood vessels (‘En bloc’) and so-called dual kidney transplants (both kidneys transplanted into a single recipient). 3. Tissue sample (biopsy) showing any of the following criteria: a. Rejection by specific immune cells (T-cells) classified as Banff grade ≥ Ia (The Banff classification is an international standard used to assess the histological changes in the transplanted kidney) b. MVI (g+ptc) = 0. (Indicates the degree of inflammation of the smallest kidney blood vessels. The value (g+ptc) = 0 means that no inflammation was detected) c. Banff lesion score v (intimal arteritis) > 0 (indicates the degree of inflammation of the inner layer of the arteries of the transplant) d. Newly developed or recurrent thrombotic microangiopathy (a condition where small blood clots form in the smallest blood vessels (arterioles and venules)). e. Polyomavirus or adenovirus nephropathy (a kidney disease caused by certain viruses). f. Newly developed or recurrent glomerular (relating to a specific part of the kidney) diseases g. Pyelonephritis (inflammation of the renal pelvis) or other kidney diseases not caused by rejection, e.g., obstructive nephropathy (kidney disorder caused by chronic urinary obstruction). h. Insufficient tissue material for examination and independent assessment by a central pathology committee. (BASEC)
Studienstandort
Basel, Zürich
(BASEC)
Sponsor
Dr. Katharina Bruppacher Biogen Switzerland AG Neuhofstrasse 30 6340 Baar
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Stacy Rangel
+14088025901
stacy.rangel@clutterbiogen.comBiogen Idec Research Limited 5 Foundation Park Roxborough Way SL6 3UD Maidenhead, Berkshire
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Nordwest- und Zentralschweiz EKNZ
(BASEC)
Datum der Bewilligung durch die Ethikkommission
24.07.2025
(BASEC)
ICTRP Studien-ID
NCT06685757 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Eine doppelblinde, placebokontrollierte, multizentrische, randomisierte Phase-III-Studie zur Beurteilung der Wirksamkeit und Sicherheit von Felzartamab bei Empfängern von Nierentransplantaten mit später Antikörper-vermittelter Abstossung (AMR) (TRANSCEND) (BASEC)
Wissenschaftlicher Titel
A Double-Blind, Placebo-Controlled, Multicenter, Randomized Phase 3 Trial Evaluating the Efficacy and Safety of Felzartamab in Kidney Transplant Recipients With Late Antibody-Mediated Rejection (AMR) (ICTRP)
Öffentlicher Titel
A Study to Learn More About the Effects and Safety of Felzartamab Infusions in Adults With Kidney Transplants Who Have Antibody-Mediated Rejection (AMR) (ICTRP)
Untersuchte Krankheit(en)
Antibody-mediated Rejection (ICTRP)
Untersuchte Intervention
Drug: FelzartamabDrug: Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
Key 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.
5. Any B cell-depleting therapy (including anti-Cluster of Differentiation 20
[CD20] agents [e.g., rituximab]) within 3 months prior to randomization.
6. Any other investigational agent within 3 months or 5 half-lives (whichever is
longer) of randomization.
Note: Other protocol-defined inclusion/exclusion criteria apply. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Part A: Percentage of Participants Who Achieve Biopsy-proven Histologic Resolution (BPHR) (ICTRP)
Part A: Microvascular Inflammation (MVI) Score;Part A: Percentage of Participants Who Achieve an MVI Score of 0;Part A: Change from Baseline in Donor-derived Cell-free DNA (dd-cfDNA);Part A: Biopsy-based Transcript Composite Score for AMR/MVI;Part A: Change from Baseline in Estimated Glomerular Filtration Rate (eGFR);Part B: Percentage of Participants Who Achieve BPHR;Part B: MVI Score;Part B: Percentage of Participants Who Achieve an MVI Score of 0;Part B: Change from Baseline in dd-cfDNA;Part B: Biopsy-based Transcript Composite Score for AMR/MVI;Part B: Change from Baseline in eGFR;Part B: Time to All-cause Allograft Loss;Parts A and B: Number of Participants with Adverse Events;Parts A and B: Number of Participants with Clinically Significant Laboratory Abnormalities;Parts A and B: Number of Participants with Clinically Significant Vital Signs Abnormalities;Parts A and B: Number of Participants with Clinically Significant ECG Abnormalities;Parts A and B: Percentage of Participants with T Cell-mediated Rejection (TCMR) by Biopsy;Parts A and B: Felzartamab Serum Concentration;Parts A and B: Number of Participants with Anti-drug Antibodies (ADAs) against Felzartamab (ICTRP)
Registrierungsdatum
11.11.2024 (ICTRP)
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Medical DirectorUS Biogen Clinical Trial Center, clinicaltrials@biogen.com, 1-866-633-4636, Biogen (ICTRP)
Sekundäre IDs
2024-519095-66-00, 299AR301 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT06685757 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar