Obinutuzumab for Kidney Disease

(MAJESTY Trial)

Recruiting at 104 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

142 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics (PK) of obinutuzumab compared with tacrolimus in participants with primary membranous nephropathy (pMN).

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 Obinutuzumab generally safe for humans?

Obinutuzumab has been studied for various conditions, and while it can cause mild to moderate infusion-related reactions (like reactions during or after the drug is given) and low white blood cell counts, these side effects are generally manageable. Hypersensitivity reactions (allergic-type reactions) are rare in humans, even though they were observed in animal studies. ^{1 2 3 4 5}

How is the drug Obinutuzumab unique for treating kidney disease?

Obinutuzumab is unique because it is a type II anti-CD20 monoclonal antibody that targets B-cells, leading to their depletion, which is not a common approach in treating kidney disease. It is designed to enhance immune-mediated cell death, making it potentially effective for conditions where B-cell activity contributes to the disease. ^{1 3 4 5 6}

What data supports the effectiveness of the drug Obinutuzumab for kidney disease?

Research shows that Obinutuzumab effectively depletes certain immune cells in patients with end-stage kidney disease, and it has been effective in treating other conditions like chronic lymphocytic leukemia and follicular lymphoma by prolonging survival and managing symptoms. ^{1 3 4 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

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 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]

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]

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 (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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Obinutuzumab Effectively Depletes Key B-cell Subsets in Blood and Tissue in End-stage Renal Disease Patients. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Obinutuzumab: first global approval. [2021]

3. France pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Obinutuzumab in Cynomolgus Monkeys and Relevance to Humans. [2018]

7. Italy pubmed.ncbi.nlm.nih.gov

Flare of a mixed cryoglobulinaemic vasculitis after obinutuzumab infusion. [2022]