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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Obinutuzumab (also known as Gazyva) to determine its effectiveness in reducing protein in the urine for individuals with Focal Segmental Glomerulosclerosis (FSGS), a kidney condition that can lead to nephrotic syndrome (characterized by high protein in urine and low blood protein). It targets patients whose condition has not improved with other treatments, such as steroids or rituximab, or those unable to take high-dose steroids. Suitable candidates for this trial have been diagnosed with FSGS, continue to have significant protein in their urine despite treatment, and are willing to try an intravenous drug. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants, offering a chance to contribute to potential advancements in FSGS treatment.

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.

Is there any evidence suggesting that Obinutuzumab is likely to be safe for humans?

Research has shown that obinutuzumab might be a safe treatment for certain kidney conditions. It helps reduce proteinuria, which occurs when there is too much protein in the urine—a sign of kidney issues. In some cases, obinutuzumab has helped patients achieve remission, significantly improving their symptoms.

Reports indicate that patients with treatment-resistant FSGS, a type of kidney disease, responded well to obinutuzumab. Specifically, one report noted that one patient experienced complete remission, while three others had partial remission, meaning their symptoms improved but did not completely disappear.

These findings suggest that obinutuzumab is generally well-tolerated and safe for these patients. However, like any treatment, side effects may occur, so discussing any concerns with the trial team is important. ^{1 2 3 4 5}

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

Unlike the standard treatments for focal segmental glomerulosclerosis (FSGS), which often include high-dose corticosteroids and other immunosuppressive drugs, obinutuzumab offers a novel approach. Obinutuzumab is a monoclonal antibody that specifically targets and depletes B-cells, which are part of the immune system that may play a role in this kidney condition. This targeted action could potentially reduce the need for broad immunosuppression and its associated side effects. Researchers are excited about obinutuzumab because it may provide a more effective and safer alternative for patients who are resistant to current treatments or cannot tolerate them.

What evidence suggests that Obinutuzumab might be an effective treatment for FSGS?

Research has shown that Obinutuzumab, which participants in this trial will receive, might be a promising treatment for people with Focal Segmental Glomerulosclerosis (FSGS). One study found that Obinutuzumab significantly reduced protein in the urine, a major issue in FSGS, especially for patients unresponsive to two or three other treatments. Another report highlighted successful results in treatment-resistant FSGS cases, with one patient achieving complete remission and three others showing improvement. These findings suggest that Obinutuzumab could effectively manage this condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Fernando Fervenza, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 (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]

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]

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, 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39396511/

Obinutuzumab May Be an Effective and Safe Option for ... Conclusion: Obinutuzumab may be an efficient and safe option for inducing remission in adult MCD and FSGS patients who presented with nephrotic ...

2. journals.lww.com journals.lww.com/jasn/fulltext/2023/11001/obinutuzumab_in_treatment_resistant_primary_focal.3461.aspx

Obinutuzumab in Treatment-Resistant Primary Focal ... Conclusions: We report 4 cases of treatment-resistant primary FSGS that were treated successfully with obinutuzumab infusions with 1 complete remission and 3 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04983888

NCT04983888 | Obinutuzumab in Primary FSGS The purpose of this study is to evaluate the safety and efficacy of Obinutuzumab in inducing complete or partial remission of proteinuria. Official Title. A ...

4. docwirenews.com docwirenews.com/post/obinutuzumab-efficacy-safety-for-fsgs-treatment

Obinutuzumab Efficacy, Safety for FSGS Treatment Overall, obinutuzumab significantly reduced proteinuria in patients with primary FSGS for whom two to three previous therapies had failed.

5. mayo.edu mayo.edu/research/clinical-trials/cls-20516467

A Study to Evaluate Obinutuzumab to Treat ... The purpose of this study is to enroll 12 patients with immunosuppression-dependent or immunosuppression/treatment-resistant primary FSGS.

6. asn-online.org asn-online.org/education/kidneyweek/2023/program-abstract.aspx?controlId=3940465

Kidney Week We report 4 cases of treatment-resistant primary FSGS that were treated successfully with obinutuzumab infusions with 1 complete remission and 3 partial ...