Obinutuzumab for Childhood-Onset Nephrotic Syndrome

(INShore Trial)

Recruiting at 61 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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This open-label, randomized multicenter study is to assess the efficacy, safety, and pharmacokinetics (PK)/pharmacodynamics (PD) of obinutuzumab compared with mycophenolate mofetil (MMF) in children and young adults (aged \>= 2-25 years) with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).

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.

What data supports the effectiveness of the drug Obinutuzumab for Childhood-Onset Nephrotic Syndrome?

Research shows that Mycophenolate Mofetil (MMF), a component of the treatment, has been effective in treating children with nephrotic syndrome, helping to reduce relapses and manage symptoms. ^{1 2 3 4 5}

Is Obinutuzumab safe for use in humans?

Obinutuzumab has been used in treating certain types of blood cancers and has shown a generally manageable safety profile, with mild to moderate infusion-related reactions (like fever or chills) being common, and low white blood cell counts (neutropenia) as a more serious side effect. ^{1 2 5 6 7}

How is the drug Obinutuzumab different from other drugs for childhood-onset nephrotic syndrome?

Obinutuzumab, combined with Mycophenolate Mofetil (MMF), offers a unique approach by targeting specific immune cells, potentially providing an alternative for children who do not respond well to standard treatments like steroids. This combination may offer a new option for managing difficult cases of nephrotic syndrome in children. ^{2 3 4 5 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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 had two or more relapses in 6 months while on MMF for at least 6 months.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A single-centre retrospective study of the safety and efficacy of mycophenolate mofetil in children and adolescents with nephrotic syndrome. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[A prospective multicenter clinical control trial on treatment of refractory nephrotic syndrome with mycophenolate mofetil in children]. [2016]

3. Canada pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil treatment of severe renal disease in pediatric onset systemic lupus erythematosus. [2016]

4. China pubmed.ncbi.nlm.nih.gov

Assessment of mycophenolate mofetil for treatment of frequently relapsing nephrotic syndrome in children. [2016]

5. China pubmed.ncbi.nlm.nih.gov

[Mycophenolate mofetil in the treatment of primary nephrotic syndrome]. [2016]

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

Obinutuzumab: first global approval. [2021]

7. France pubmed.ncbi.nlm.nih.gov

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

8. Germany pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome. [2018]