Obinutuzumab for Focal Segmental Glomerulosclerosis

Overseen By Stanton Amber

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Cyclophosphamide

Disqualifiers: Genetic FSGS, Hepatitis, HIV, others

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

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: 2

Duration: 6 months

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called Obinutuzumab to see if it can help reduce protein levels in the urine of patients with kidney problems. The medication works by helping the immune system target and attack harmful cells. The goal is to find out if it is safe and effective for these patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients who are resistant or dependent on certain therapies, like corticosteroids, are eligible, which might suggest you can continue some treatments.

What data supports the effectiveness of the drug Obinutuzumab for Focal Segmental Glomerulosclerosis?

Obinutuzumab has shown effectiveness in treating certain types of blood cancers, like chronic lymphocytic leukemia and follicular lymphoma, by targeting and killing specific immune cells. While it hasn't been directly studied for Focal Segmental Glomerulosclerosis, its ability to deplete key B-cell subsets in patients with end-stage renal disease suggests potential benefits for kidney-related conditions. ^{1 2 3 4 5}

Is Obinutuzumab generally safe for humans?

Obinutuzumab, also known as Gazyva, has been studied for safety in humans, primarily for blood cancers. Common side effects include mild to moderate reactions during infusion, like fever or chills, and low white blood cell counts. Serious allergic reactions are rare in humans, even though they were observed in animal studies. ^{1 2 3 4 6}

How is the drug Obinutuzumab unique for treating Focal Segmental Glomerulosclerosis?

Obinutuzumab is unique because it is a type II anti-CD20 monoclonal antibody that targets B-cells, which are part of the immune system, and it is glycoengineered to enhance its ability to kill these cells. This mechanism is different from other treatments for Focal Segmental Glomerulosclerosis, which may not specifically target B-cells or use this advanced engineering to increase effectiveness. ^{1 2 3 4 6}

Research Team

Fernando Fervenza, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults with FSGS, a kidney disease causing protein loss in urine and low blood albumin levels. Participants must have tried other treatments without success or cannot take high-dose steroids. Excluded are those with genetic FSGS, infections like hepatitis or HIV, pregnant/breastfeeding women, severe anemia or low platelets, and recent recipients of certain drugs.

Inclusion Criteria

My kidney biopsy showed FSGS.

My condition hasn't improved with standard treatments, or I can't take high dose steroids.

I have nephrotic syndrome with high protein in urine and low blood albumin levels.

Exclusion Criteria

Your hemoglobin level is less than 8.0 grams per deciliter.

I agree to use highly effective contraception during and 6 months after treatment.

I have had a kidney transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab 1 gram on day 1 and 1 gram on day 15, given intravenously, with an identical course at 6 months

6 months

2 visits (in-person) for each course

Follow-up

Participants are monitored for safety and effectiveness after treatment, including remission status and proteinuria levels

18 months

Treatment Details

Interventions

• Obinutuzumab

Trial Overview The trial is testing Obinutuzumab's ability to reduce proteinuria (protein in urine) for patients with primary FSGS. It aims to see if the drug can induce complete or partial remission of this condition.

Participant Groups

Group I: Primary Focal Segmental Glomerulosclerosis (FSGS) Experimental Treatment 1 Intervention

Subjects with immunosuppression-dependent or immunosuppression/treatment-resistant primary FSGS or contraindication/patient refusal to take high dose corticosteroids, will receive obinutuzumab 1 gram on day 1 and 1 gram on day 15, given intravenously and then an identical course at 6 months.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

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]

Obinutuzumab, a glycoengineered anti-CD20 monoclonal antibody, shows improved clinical efficacy compared to rituximab in treating non-Hodgkin lymphoma, with a phase I/II study involving patients receiving doses up to 2000 mg.

The study found that a dosing regimen of 1600/800 mg resulted in greater tumor shrinkage without increasing adverse events, leading to the identification of a 1000 mg fixed-dose regimen for further phase III evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma. Cartron, G., Hourcade-Potelleret, F., Morschhauser, F., et al.[2022]

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 (G) combined with chemotherapy (G + Chemo) is shown to be a cost-effective treatment for previously untreated follicular lymphoma (FL) in Japan, with incremental cost-effectiveness ratios (ICERs) below the acceptable threshold of 7.5 million JPY per quality-adjusted life year (QALY).

The study found that the lowest lifetime direct medical costs were associated with the R-bendamustine (R-B) treatment group, primarily due to reduced hospitalization costs, highlighting the impact of treatment settings on overall expenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. Ohno, S., Shoji, A., Hatake, K., et al.[2021]

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]

References

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

Obinutuzumab: first global approval. [2021]

2. France pubmed.ncbi.nlm.nih.gov

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

3. Italy pubmed.ncbi.nlm.nih.gov

Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma. [2022]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. [2021]

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

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