Obinutuzumab for Kidney Disease

(MAJESTY Trial)

Not currently recruiting at 124 trial locations

Overseen By Reference Study ID Number: WA41937 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Anti-CD20, Cyclophosphamide, Tacrolimus, Cyclosporin

Disqualifiers: Secondary MN, Diabetes, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a medication called obinutuzumab for individuals with primary membranous nephropathy (pMN), a kidney disease. The study compares obinutuzumab to tacrolimus to determine which is more effective and safe. Participants will be randomly assigned to receive either obinutuzumab or tacrolimus, and researchers will monitor the effects on the kidneys. Suitable candidates have been diagnosed with pMN and exhibit high protein levels in their urine despite receiving optimal care for several months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity 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 taking your current medications, but you cannot have taken certain therapies like anti-CD20, cyclophosphamide, tacrolimus, or cyclosporin within 6 to 9 months before screening.

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

Research has shown that obinutuzumab has been tested for safety in treating kidney-related diseases. In one study, 83.6% of patients experienced clinical remission, significantly improving their symptoms. The same study found that obinutuzumab helped lower protein levels in urine, a positive indicator for kidney health.

Another study focused on obinutuzumab in patients with lupus, a disease that can affect the kidneys. It found that 46.4% of patients experienced complete improvement in kidney health, compared to a 33.1% improvement in the placebo group.

Obinutuzumab has FDA approval for other conditions, indicating a known safety record. However, like any treatment, it may have side effects. Prospective participants should discuss any concerns with the trial team before joining. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney disease?

Most treatments for kidney disease, like tacrolimus, work by broadly suppressing immune activity to reduce inflammation. However, obinutuzumab works differently by specifically targeting and depleting B-cells, a key player in the immune response that can contribute to kidney damage. This targeted action could potentially offer a more precise approach to managing the condition with fewer side effects. Researchers are excited about obinutuzumab because its unique mechanism may lead to more effective and safer treatment outcomes for patients with kidney disease.

What evidence suggests that this trial's treatments could be effective for primary membranous nephropathy?

Research has shown that obinutuzumab, which participants in this trial may receive, can help treat kidney-related diseases. Studies have found that it lowers the risk of kidney function decline by 60% and helps maintain kidney health. In patients with lupus nephritis, obinutuzumab significantly improved kidney health, with 46.4% of patients experiencing a complete recovery of kidney function, compared to 33.1% of those who received a placebo. The treatment reduces harmful B cells, preventing further kidney damage. This suggests that obinutuzumab might also benefit people with primary membranous nephropathy (pMN), another kidney condition. Another group in this trial will receive tacrolimus, studied as an active comparator. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with primary membranous nephropathy, a kidney condition diagnosed by biopsy. Participants must have significant protein in their urine despite supportive care and adequate kidney function. Exclusions include pregnancy, recent major surgery, intolerance to study drugs, severe renal impairment or dialysis need, diabetes, certain prior treatments including anti-CD20 therapy or immunosuppressants within specified time frames before screening.

Inclusion Criteria

My kidney function is adequate based on tests.

Other inclusion criteria may apply

My kidney biopsy confirmed I have primary membranous nephropathy.

Exclusion Criteria

I have type 1 or type 2 diabetes.

I have not had major surgery in the last 4 weeks.

I do not have any severe illnesses that would stop me from joining the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label treatment with either obinutuzumab or tacrolimus based on randomization

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab

Trial Overview The trial tests the effectiveness and safety of Obinutuzumab against Tacrolimus in treating primary membranous nephropathy. It also examines how the body processes these drugs (pharmacodynamics) and their movement through the body (pharmacokinetics). Patients will receive additional medications like Methylprednisolone, Diphenhydramine, and Acetaminophen to manage reactions.

How Is the Trial Designed?

Group I: Open Label Treatment: Obinutuzumab Experimental Treatment 4 Interventions

Participants will be randomized at a 1:1 ratio to receive open-label treatment with obinutuzumab according to region and anti-phospholipase A2 receptor (PLA2R) autoantibody titer (using Euroimmun ELISA).

Group II: Open Label Treatment: Tacrolimus Active Control 1 Intervention

Participants will be randomized at a 1:1 ratio to receive open-label treatment with tacrolimus according to region and anti-PLA2R autoantibody titer (using Euroimmun ELISA).

Obinutuzumab is already approved in United States, European Union for the following indications:

Approved in United States as Gazyva for:

• Chronic Lymphocytic Leukemia (CLL)
• Follicular Lymphoma

Approved in European Union as Gazyva for:

• Chronic Lymphocytic Leukemia (CLL)
• Follicular Lymphoma

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

In preclinical studies involving cynomolgus monkeys, obinutuzumab caused expected B-cell depletion but also led to hypersensitivity reactions, indicating potential safety concerns that were observed at all doses.

Despite these reactions in monkeys, clinical evidence suggests that hypersensitivity to obinutuzumab is rare in humans, highlighting that animal studies may not always predict human responses to immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Obinutuzumab in Cynomolgus Monkeys and Relevance to Humans. Husar, E., Solonets, M., Kuhlmann, O., et al.[2018]

Obinutuzumab, an anti-CD20 antibody, effectively induces a rapid loss of various B-cell subsets in patients with end-stage renal disease, demonstrating its potential to target B cells in the immune system.

The treatment was associated with increased levels of B cell-activating factor and decreased CXCL13, suggesting a significant impact on B-cell activity that could enhance its efficacy in conditions like lupus, where traditional B-cell therapies face challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab Effectively Depletes Key B-cell Subsets in Blood and Tissue in End-stage Renal Disease Patients. Looney, CM., Schroeder, A., Tavares, E., et al.[2023]

Obinutuzumab (OBZ) was used to treat a patient with refractory cryoglobulinaemic vasculitis (CV) who was immunized against rituximab (RTX), and no cross-reactivity between anti-RTX antibodies and OBZ was found, suggesting OBZ can be a viable alternative.

The patient experienced a flare of CV after OBZ infusion, which may be linked to the release of immune complexes due to B cell lysis, indicating that the use of OBZ in patients with mixed CV should be approached with caution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flare of a mixed cryoglobulinaemic vasculitis after obinutuzumab infusion. Martin de Fremont, G., Chiron, A., Krzysiek, R., et al.[2022]

Obinutuzumab, combined with bendamustine, significantly prolonged progression-free survival (PFS) in patients with indolent non-Hodgkin's lymphoma, particularly benefiting those with follicular lymphoma, as shown in the phase III GADOLIN study.

The treatment was generally well-tolerated, with mild to moderate infusion-related reactions being the most common side effects, while neutropenia was the most frequent severe adverse event, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. Dhillon, S.[2018]

In a multinational phase III study, obinutuzumab combined with chlorambucil significantly improved progression-free survival and event-free survival in adults with previously untreated chronic lymphocytic leukaemia (CLL) compared to chlorambucil alone and rituximab plus chlorambucil.

Obinutuzumab plus chlorambucil had a manageable safety profile, with neutropenia and infusion-related reactions being the most common serious side effects, primarily occurring during the first infusion and generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia. Hoy, SM.[2018]

Obinutuzumab is an effective treatment for B-cell malignancies, specifically approved in the US for chronic lymphocytic leukaemia (CLL) in combination with chlorambucil, showcasing its efficacy in targeting cancer cells.

Utilizing GlycoMAb® technology, obinutuzumab enhances immune-mediated cell death through increased antibody-dependent cellular cytotoxicity, making it a promising option in ongoing phase III trials for various B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: first global approval. Cameron, F., McCormack, PL.[2021]

Citations

1. roche.com roche.com/media/releases/med-cor-2025-10-20

FDA approves Roche's Gazyva/Gazyvaro for the treatment ... Data suggests that Gazyva/Gazyvaro depletes disease-causing B cells, helping to limit further damage to the kidneys and potentially preventing ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2410965

Efficacy and Safety of Obinutuzumab in Active Lupus ... A complete renal response at week 76 was observed in 46.4% of the patients in the obinutuzumab group and 33.1% of those in the placebo group ( ...

3. gene.com gene.com/media/press-releases/15086/2025-10-27/positive-phase-iii-results-for-genentech

Genentech: Press Releases | Monday, Oct 27, 2025 “These results show that Gazyva may achieve robust disease control with a reduced need for corticosteroids, which are associated with serious ...

4. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42734

Kidney Outcomes and Preservation of Kidney Function With ... Obinutuzumab reduced the risk of developing the composite kidney outcome by 60%, LN flare by 57%, and first eGFR decline of 30% or 40% by 80% ...

5. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/gazyva-gazyvaro-complete-renal-response-patients-lupus-nephritis

Gazyva/Gazyvaro Shows Improved Complete Renal ... “Gazyva/Gazyvaro achieved a robust complete renal response rate in lupus nephritis, which is associated with long-term preservation of kidney ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40918120/

Efficacy and safety of obinutuzumab in primary ... 46/55(83.6%) patients achieved clinical remission (including 40.0% of PR and 43.6% of CR), with significantly reduced proteinuria and increased ...

7. gene.com gene.com/media/press-releases/15085/2025-10-19/fda-approves-genentechs-gazyva-for-the-t

Genentech: Press Releases | Sunday, Oct 19, 2025 Data suggests that Gazyva depletes disease-causing B cells, helping to limit further damage to the kidneys and potentially preventing or ...