Antibody-mediated Rejection
Conditions
Keywords
AMR, Felzartamab, Kidney Transplant
Brief summary
In this study, researchers will learn more about a drug called felzartamab in people who have received a kidney transplant and then developed a condition called antibody-mediated rejection (AMR). AMR happens when the body's immune system creates antibodies that attack the transplanted kidney. In late AMR, this happens more than 6 months after the kidney transplant. It can lead to serious kidney problems over time. An earlier study called 299AR301 (TRANSCEND) began in 2024 and is investigating felzartamab in participants with AMR. It includes a treatment period of about 1 year. It first compares treatment with felzartamab to placebo for about 6 months and then all participants are given felzartamab to complete the study. This study, 299AR301 LTE, is a long-term extension of the parent study 299AR301. Participants who join this study will have the opportunity to receive felzartamab for up to 4 more years. The goals of this study are to learn more about the long-term safety and effects of felzartamab in people with AMR. This study is part of a group of studies looking at long-term felzartamab use in people with organ transplants. This study is a substudy of the main study 299AR302. The main question researchers will answer relate to safety. Namely, how many participants have adverse events during the study and how lab test results change over time. Adverse events are health problems that may or may not be caused by the study drug. Researchers will perform kidney biopsies to track kidney health. Researchers will also study how felzartamab affects kidney inflammation, kidney function, immune activity, and overall health. The study will be done as follows: * Participants who complete the final visit of the treatment period in the parent study can enroll in this study. This includes participants who stopped receiving felzartamab early but still attended their final visits. * Participants who did not stop receiving felzartamab in the parent study will continue to receive felzartamab for up to 4 more years in this study. Participants may also stop felzartamab during this study at any time. * Participants who stopped receiving felzartamab in the parent study will only attend study visits for health monitoring- they will not receive felzartamab. * Felzartamab will be given as an intravenous (IV) infusion, which is a slow injection into a vein using a needle. * Participants receiving felzartamab may have up to 27 study visits over 200 weeks with an additional safety follow-up visit 4 weeks after their final dose. * Participants who are not receiving felzartamab may have up to 9 study visits over 200 weeks.
Detailed description
The primary objective of this study is to evaluate the long-term safety of felzartamab. The secondary objectives of this study are to describe the ongoing efficacy of felzartamab on biopsy-proven histologic response (BPHR), microvascular inflammation (MVI) and graft function; to evaluate the ongoing efficacy of felzartamab by monitoring circulating donor-derived cell-free DNA (dd-cfDNA) and to evaluate pharmacokinetics (PK) and immunogenicity of felzartamab.
Interventions
DRUGFelzartamab
Administered IV
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Have met all eligibility criteria for the Master Protocol. * Have completed the parent study Week 52 visit or will be completing all Week 52 visit procedures (for participants who sign consent before reaching the Week 52 visit). * Have received at least one dose of felzartamab in the parent study. Participants who discontinued study treatment prior to receiving any doses of felzartamab in the parent study (i.e., those in the placebo group who discontinued before receiving felzartamab) are not eligible for enrollment in this substudy. * For participants enrolling into this study who have not discontinued felzartamab treatment in the parent study only: The Investigator has determined that the participant could benefit from continued felzartamab treatment. Key
Exclusion criteria
* Met a treatment discontinuation criterion in the parent study but treatment was not discontinued (for example, because the criterion was met after the last dose of felzartamab in the parent study). Note: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | From first dose of study drug up to end of study follow-up (Up to Week 204) |
| Number of Participants who Discontinue Treatment due to an AE | From first dose of study drug up to end of study follow-up (Up to Week 204) |
| Number of Participants with Clinically Significant Laboratory, Vital Signs and Electrocardiograms (ECGs) Abnormalities | From first dose of study drug up to end of trial visit (up to Week 200) |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants Achieving Biopsy-proven Histologic Resolution (BPHR) | Up to Week 200 |
| Microvascular Inflammation (MVI) Score | Up to Week 200 |
| Percentage of Participants Achieving an MVI Score of 0 | Up to Week 200 |
| Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) | Baseline, Week 200 |
| Time to All-cause Allograft Loss | Up to Week 200 |
| Time to Death Censored Allograft Loss | Up to Week 204 |
| Change From Baseline in Absolute and Fraction Levels of Donor-derived Cell-free DNA (dd-cfDNA) | Up to Week 200 |
| Felzartamab Serum Concentration | At Week 200 |
| Number of Participants with Anti-drug Antibodies (ADAs) Against Felzartamab | At Week 200 |
Contacts
CONTACTUS Biogen Clinical Trial Center
CONTACTGlobal Biogen Clinical Trial Center
STUDY_DIRECTORMedical Director
Biogen
Outcome results
None listed