Felzartamab for Membranous Nephropathy

(PROMINENT Trial)

Recruiting at 19 trial locations

Overseen By US Biogen Clinical Trial Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Biogen

Must be taking: ACEI or ARB

Disqualifiers: Secondary MN, Severe renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 35

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how felzartamab can help individuals with primary membranous nephropathy (PMN), a kidney condition where the immune system mistakenly attacks the kidney's filters, causing damage. Researchers seek to determine if felzartamab can reduce protein leakage into urine and maintain kidney function, comparing it to the existing treatment, tacrolimus. Participants will receive either felzartamab through IV infusions or tacrolimus tablets orally. This trial may suit those diagnosed with PMN who experience symptoms like swelling or tiredness and require immune-suppressing treatment. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, you must be on a stable dose of certain blood pressure medications (ACEI or ARB) for at least 3 months before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In previous studies, patients have generally tolerated felzartamab well. Research shows that its safety profile remains consistent, behaving predictably in the body. Specifically, an earlier study in patients with antibody-related kidney conditions found that felzartamab did not cause unexpected side effects. Common side effects reported were minor, including tiredness or mild reactions at the infusion site.

Felzartamab is a monoclonal antibody, a lab-made protein that targets and reduces certain immune cells. This is crucial for conditions like PMN, where the immune system mistakenly attacks the kidneys. Although felzartamab is still under study and not yet approved by health authorities, early safety data suggests it is generally safe for use. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for membranous nephropathy?

Felzartamab is unique because it targets CD38, a protein found on the surface of certain immune cells, which is not a focus of current standard treatments like corticosteroids or calcineurin inhibitors such as tacrolimus. By aiming directly at CD38, felzartamab potentially offers a more precise mechanism to reduce kidney inflammation associated with membranous nephropathy. Researchers are excited about felzartamab because this targeted approach might improve symptoms with fewer side effects compared to broader immunosuppressive therapies.

What evidence suggests that felzartamab might be an effective treatment for membranous nephropathy?

Studies have shown that felzartamab can quickly lower protein levels in the urine of patients with primary membranous nephropathy (PMN). Research indicates that this drug can partially improve proteinuria, reducing protein leakage into the urine. In some cases, felzartamab has led to significant improvements in patients' conditions. Specifically, previous studies found that nearly half of the patients taking felzartamab experienced partial remission, with reduced protein levels in their urine. This trial will evaluate felzartamab as a potential treatment for reducing kidney damage caused by PMN, with participants receiving either felzartamab or oral tacrolimus in the Open-Label Treatment Phase. ^{1 3 4 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

Adults with primary membranous nephropathy (PMN) who have high levels of protein in their urine despite receiving supportive care for at least 3 months. This includes those newly diagnosed or those who relapsed after treatment. Participants must be on the highest dose they can tolerate of specific blood pressure medications and need immune system therapy as judged by a doctor.

Inclusion Criteria

I have PMN, need treatment, and my diagnosis was confirmed by a kidney biopsy or positive anti-PLA2R antibodies.

I have positive anti-PLA2R antibodies and haven't had a kidney biopsy in the last 5 years.

I have never received immune system therapy for my newly diagnosed condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Open-Label Treatment

Participants receive either felzartamab as intravenous infusions or tacrolimus orally

104 weeks

Up to 23 visits

Non-Responder Treatment

Participants who meet rescue criteria may receive regional standard of care immunosuppressive therapy or additional doses of felzartamab

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 52 weeks

Follow-up visits every 12 weeks until Week 104

What Are the Treatments Tested in This Trial?

Interventions

• Felzartamab

Trial Overview The study is testing felzartamab, a lab-made antibody designed to target immune cells causing kidney damage in PMN, against tacrolimus, an existing drug for PMN. Researchers will compare effects on urine protein levels and kidney function over 104 weeks, with some participants potentially followed up to 156 weeks if needed.

How Is the Trial Designed?

Group I: Open-Label Treatment Phase Experimental Treatment 2 Interventions

Participants will receive several intravenous (IV) doses of felzartamab or oral tacrolimus in the Open-Label Treatment Phase.

Group II: Non-Responder Treatment Phase Experimental Treatment 2 Interventions

Participants initially randomized to felzartamab or tacrolimus who meet rescue criteria may receive regional standard of care immunosuppressive therapy (IST) per Investigator discretion or several IV doses of felzartamab, respectively, in the Non-Responder Treatment Phase.

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Citations

1. kidney-international.org kidney-international.org/article/S0085-2538(25)00488-0/fulltext

Randomized, double-blind, placebo-controlled phase 2a ... Treatment with felzartamab versus placebo led to rapid (within 3–6 months) reduction in least-squares mean UPCR sustained at nine months (placebo, –5.7%; 2-dose ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11403052/

Phase 1b/2a Study Assessing the Safety and Efficacy of ... Felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some ...

3. investors.biogen.com investors.biogen.com/news-releases/news-release-details/biogen-initiates-phase-3-study-felzartamab-treatment-primary

Biogen Initiates Phase 3 Study of Felzartamab for the ... The Phase 3 study will evaluate the efficacy and safety of the investigational drug felzartamab compared to tacrolimus in adults diagnosed with primary ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06962800

NCT06962800 | A Study to Learn More About the Effects ... The primary objective of the study is to assess the efficacy of felzartamab compared to tacrolimus in participants with PMN in achieving complete remission (CR) ...

5. journals.lww.com journals.lww.com/jasn/fulltext/2023/11001/safety_and_efficacy_of_felzartamab_in_primary.28.aspx

Safety and Efficacy of Felzartamab in Primary Membranous... 1). Of the patients who received >5 Felza doses and no other IST, 7/15 (47%) patients in C1 and 2/11 (18%) patients in C2 achieved partial remission (UPCR ...

6. kireports.org kireports.org/article/S2468-0249(24)01794-7/fulltext

Phase 1b/2a Study Assessing the Safety and Efficacy of ... An open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ ...