A Study to Learn More About the Effects and Safety of Felzartamab Infusions in Adults With Kidney Transplants Who Have Antibody-Mediated Rejection (AMR)
In this study, researchers will learn more about the use of felzartamab in kidney transplant patients who have antibody-mediated rejection, also known as AMR. Kidney transplants can save lives for people with kidney failure. But even after a successful transplant, the body's immune system can sometimes attack the new kidney.
Antibody-mediated rejection (AMR) is when a person's immune system attacks a transplanted organ, like a new kidney. In the person receiving the transplant, their immune system creates specific antibodies. Antibodies are proteins that help the body fight infections.
In people with AMR, these antibodies mistakenly see the new organ as a threat and damage its blood vessels. This can cause the new organ to fail. In this study, researchers will learn more about how a study drug called felzartamab affects people with AMR.
Felzartamab is a monoclonal antibody, which means it is an antibody made in a laboratory. Felzartamab can target immune cells that produce antibodies, helping to lower their buildup in the kidneys. The main goal of this study is to compare how felzartamab works in participants with kidney transplants who experience AMR compared to a placebo.
A placebo is something that looks like the study drug but does not contain any medicine. A placebo is also given in the same way as the study drug. All participants in this study will have active AMR or AMR that has lasted for at least 6 months after their kidney transplant.
The main question that researchers want to answer is: • How many participants have biopsy results showing that their transplanted kidney tissue looks normal or near normal after 24 weeks of treatment? Researchers will also learn about: * How long it takes before the participants' disease gets worse * How long the participants' urine protein levels stay low * Kidney biopsy scores to check for blood vessel inflammation at 6 months and 1 year * How many people have no blood vessel inflammation at these times * Changes in donor deoxyribonucleic acid (DNA) levels in blood from the start of treatment * Biopsy test scores for signs of rejection and inflammation at 6 months and 1 year * Changes in kidney function from the start of treatment * How many people have biopsy results showing their kidney tissue looks normal again * How long the transplanted kidney keeps working * How many participants have medical problems during the study * How many participants show signs of another type of kidney transplant rejection called T-cell-mediated rejection (TCMR) at Week 24 and Week 52 * How do results from vital signs, electrocardiograms (ECGs), and blood and urine tests change over time * How felzartamab is processed by the body * How many participants develop antibodies against felzartamab in the blood The study will be done as follows: * Participants will be screened to check if they can join the study. This will take up to 42 days. * There will be 2 parts in this study.
* Part A of the study is "double blind. " This means that neither the participants, study doctor, or site staff know if the participants received the study drug or a placebo. During Part A, participants will be randomized to receive up to 9 doses of either felzartamab or placebo.
* Part B of the study is "open label. " This means that the participants, study doctor, and site staff know which study drug the participant is receiving. During Part B, all participants from Part A will receive up to 9 doses of felzartamab.
* All doses will be given through an "intravenous" infusion. This means it will be given into a vein. The dose the participants receive will depend on their body weight.
* Part A will last up to 24 weeks. Part B will last up to 28 weeks. In total, participants will have up to 21 study visits and will be in the study for about 1 year.
Study details:
The primary objective of this study is to evaluate the efficacy of felzartamab compared to placebo in kidney transplant recipients diagnosed with active or chronic active AMR. The secondary objectives of this study are: Part A: To evaluate the efficacy of felzartamab compared to placebo through additional clinical endpoints; Part B: To summarize felzartamab efficacy at Week 52 in kidney transplant recipients diagnosed with active or chronic active AMR; Parts A and B: To evaluate the safety of felzartamab in kidney transplant recipients diagnosed with active or chronic AMR and to assess the pharmacokinetic (PK) profile and immunogenicity of felzartamab.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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.
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.
- e. Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06685757
Intervention or treatment
DRUG: Felzartamab
DRUG: Placebo
Conditions
- Antibody-mediated Rejection
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Westmead Hospital
Select from list below to view details:
Westmead Hospital
Sydney, New South Wales, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia
Princess Alexandra Hospital
Woolloongabba, Australia
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Who is running the clinical trial?
Biogen
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Felzartamab
| Drug: Felzartamab |
PLACEBO_COMPARATOR: Placebo
| Drug: Placebo |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Percentage of Participants Who Achieve Biopsy-proven Histologic Resolution (BPHR) | Not Specified | Week 24 |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Microvascular Inflammation (MVI) Score | Not Specified | Week 24 |
| Part A: Percentage of Participants Who Achieve an MVI Score of 0 | Not Specified | Week 24 |
| Part A: Change from Baseline in Donor-derived Cell-free DNA (dd-cfDNA) | Not Specified | Baseline, Week 24 |
| Part A: Change from Baseline in Biopsy-based Transcript Composite Score for AMR/MVI | Not Specified | Baseline, Week 24 |
| Part A: Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) | Not Specified | Baseline, Week 24 |
| Part B: Percentage of Participants Who Achieve BPHR | Not Specified | Weeks 24 and 52 |
| Part B: MVI Score | Not Specified | Weeks 24 and 52 |
| Part B: Percentage of Participants Who Achieve an MVI Score of 0 | Not Specified | Weeks 24 and 52 |
| Part B: Change from Baseline in dd-cfDNA | Not Specified | Baseline, Weeks 24 and 52 |
| Part B: Change from Baseline in Biopsy-based Transcript Composite Score for AMR/MVI | Not Specified | Baseline, Weeks 24 and 52 |
| Part B: Change from Baseline in eGFR | Not Specified | Baseline, Weeks 24 and 52 |
| Part B: Time to All-cause Allograft Loss | Not Specified | Up to Week 52 |
| Parts A and B: Number of Participants with Adverse Events | Not Specified | From time of first dose to end of trial visit (Up to Week 52) |
| Parts A and B: Number of Participants with Clinically Significant Laboratory Abnormalities | Not Specified | From time of first dose to end of trial visit (Up to Week 52) |
| Parts A and B: Number of Participants with Clinically Significant Vital Signs Abnormalities | Not Specified | From time of first dose to end of trial visit (Up to Week 52) |
| Parts A and B: Number of Participants with Clinically Significant ECG Abnormalities | Not Specified | From time of first dose to end of trial visit (Up to Week 52) |
| Parts A and B: Percentage of Participants with T Cell-mediated Rejection (TCMR) by Biopsy | Not Specified | Weeks 24 and 52 |
| Parts A and B: Felzartamab Serum Concentration | Not Specified | Up to Week 52 |
| Parts A and B: Number of Participants with Anti-drug Antibodies (ADAs) against Felzartamab | Not Specified | Baseline, up to Week 52 |
References
Clinical Trials Gov: A Study to Learn More About the Effects and Safety of Felzartamab Infusions in Adults With Kidney Transplants Who Have Antibody-Mediated Rejection (AMR)Other trials to consider
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