Obinutuzumab for Childhood-Onset Nephrotic Syndrome

(INShore Trial)

Not currently recruiting at 84 trial locations

Overseen By Reference Study ID Number: WA43380 https://forpatients.roche.com/

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Oral corticosteroids

Must not be taking: Other immunosuppressives

Disqualifiers: Secondary nephrotic syndrome, Steroid resistance, Genetic defects, 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: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well the drug obinutuzumab works compared to mycophenolate mofetil (MMF) in treating children and young adults with frequently relapsing or steroid-dependent nephrotic syndrome, a kidney condition causing severe swelling and protein loss in urine. The study aims to determine which treatment is safer and more effective. Participants will receive obinutuzumab through an IV or take MMF orally. It suits those diagnosed with this condition before age 18, who are in complete remission (no swelling or protein in urine), and have experienced at least one relapse in the past six months. As a Phase 3 trial, this study 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 taking your current medications, but you cannot have taken certain immunosuppressive medications other than MMF or oral corticosteroids within 2 months before joining the study.

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

Research has shown that obinutuzumab is generally well-tolerated in children with nephrotic syndrome. Studies found its safety profile similar to that in adults, with no new safety concerns, meaning the side effects were expected and manageable.

MMF, another medication used in this trial, is well-known and often prescribed for other conditions, such as in organ transplant patients. It has a well-documented safety record. Most people tolerate it well, though some may experience mild to moderate side effects, like stomach upset or changes in blood counts.

Both treatments have demonstrated considerable safety based on previous research. However, discussing any concerns or specific health conditions with a doctor before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about obinutuzumab for childhood-onset nephrotic syndrome because it offers a new mechanism of action by targeting CD20 proteins on B cells, which are involved in the immune response that can lead to kidney damage. Unlike standard treatments like corticosteroids and calcineurin inhibitors, obinutuzumab is a monoclonal antibody that could provide a more targeted approach to reducing inflammation and protein loss in the urine. Additionally, its administration through IV infusion may offer a convenient dosing schedule compared to daily oral medications, potentially improving adherence and outcomes for young patients.

What evidence suggests that this trial's treatments could be effective for nephrotic syndrome?

Research has shown that obinutuzumab, which participants in Group A of this trial will receive, may effectively treat childhood-onset nephrotic syndrome. One study found that 68% of children remained in remission after receiving obinutuzumab, compared to only 10%-25% with rituximab. Other studies have found that children treated with obinutuzumab experienced longer periods without disease recurrence and required fewer steroids, which can have serious side effects. These findings suggest that obinutuzumab could be a strong option for managing the disease. ^{1 3 5 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 children and young adults aged 2-25 with frequently relapsing or steroid-dependent nephrotic syndrome diagnosed before age 18. Participants must be in remission, have normal kidney function, and not have received certain treatments recently. They should agree to contraception if applicable and cannot join if they've had transplants, intolerances to study drugs, significant other diseases, active infections, immunodeficiencies including HIV, recent major surgery or cancer history within 5 years.

Inclusion Criteria

I am in complete remission with no swelling, low protein in my urine, and recent tests showing minimal to no protein.

I had at least one relapse in the past 6 months despite being on or after stopping steroids or immunosuppressants.

I am a male and agree to either not have sex or use birth control, and not donate sperm for 3 months after my last MMF dose.

Exclusion Criteria

I have a genetic condition known to cause severe kidney issues.

I haven't been in another drug trial within the last 30 days or 5 half-lives of the drug.

I do not have any major health issues 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 in Group A receive obinutuzumab via IV infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26). Participants in Group B receive oral MMF to Week 52.

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MMF
• Obinutuzumab

Trial Overview

The study compares the effectiveness and safety of obinutuzumab versus mycophenolate mofetil (MMF) in managing nephrotic syndrome that often relapses or depends on steroids. It's an open-label trial where everyone knows which treatment they're getting. The participants' response to treatment will also be measured through PK/PD assessments.

How Is the Trial Designed?

Group I: Obinutuzumab (Group A) Experimental Treatment 5 Interventions

Participants in Group A will receive obinutuzumab 1000 milligrams (mg) (or 20 mg/ kilogram \[kg\] for participants \<45 kg) administered by intravenous (IV) infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).

Group II: MMF (Group B) Active Control 2 Interventions

Participants in Group B will receive oral MMF 600 mg/m\^2 twice a day (BID) (target 1200 mg/m2/day in divided doses, maximum 2 g/day) to Week 52.

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

Approved in United States as Cellcept for:

• Prevention of organ rejection in kidney transplant patients
• Prevention of organ rejection in liver transplant patients
• Prevention of organ rejection in heart transplant patients

Approved in European Union as Cellcept for:

• Prevention of acute transplant rejection in adult patients receiving allogeneic kidney, liver or heart transplants

Approved in Canada as Cellcept for:

• Prevention of organ rejection in kidney transplant patients
• Prevention of organ rejection in liver transplant patients
• Prevention of organ rejection in heart transplant patients

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

Mycophenolate mofetil (MMF) combined with prednisone significantly reduced urine protein levels and increased serum albumin in patients with refractory nephrotic syndrome, with all patients having minor lesions achieving clinical remission.

The treatment was generally safe, with manageable side effects; however, one patient had to withdraw due to decreased hemoglobin, while renal function remained stable throughout the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mycophenolate mofetil in the treatment of primary nephrotic syndrome]. Zhao, M., Chen, X., Chen, Y., et al.[2016]

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 study of 11 children with lupus nephritis treated with mycophenolate mofetil (MMF) for an average of 9.8 months, the treatment showed significant effectiveness in reducing disease activity, as indicated by a marked decrease in SLEDAI scores for 10 out of 11 patients.

MMF was particularly effective in normalizing renal function in patients with membranous glomerulonephritis, while its efficacy was limited in those with proliferative glomerulonephritis, highlighting its potential as a steroid-sparing alternative for certain types of lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil treatment of severe renal disease in pediatric onset systemic lupus erythematosus. Buratti, S., Szer, IS., Spencer, CH., et al.[2016]

Citations

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Positive phase III results for Roche's Gazyva/Gazyvaro in ...

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Obinutuzumab Looks Favorable for Childhood-Onset ...

“These results show that Gazyva may achieve robust disease control with a reduced need for corticosteroids, which are associated with serious ...

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Clinical trial for Childhood Nephrotic Syndrome, Childhoo...

The purpose of this clinical trial is to compare the effects, good or bad, of obinutuzumab versus MMF in people with childhood-onset idiopathic nephrotic ...

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pmc.ncbi.nlm.nih.gov/articles/PMC10723921/

Treating Frequently Relapsing and Steroid-Dependent ...

After 2 years, 68% of children remained in remission after obinutuzumab versus only 10%–25% after rituximab in several observational studies.

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trial.medpath.com/news/dbe9cc92ae26dd11/genentech-s-gazyva-shows-significant-efficacy-in-phase-iii-trial-for-pediatric-idiopathic-nephrotic-syndrome

Genentech's Gazyva Shows Significant Efficacy in Phase III ...

Patients receiving Gazyva showed increased overall relapse-free survival, extended median time to relapse or death, significant reduction in ...

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This open-label, randomized multicenter study is to assess the efficacy, safety, and pharmacokinetics (PK)/pharmacodynamics (PD) of obinutuzumab compared ...

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These results identified low-dose obinituzumab as a promising treatment option in children with steroid-dependent or frequently relapsing nephrotic syndrome.