Obinutuzumab for Lupus Nephritis

(POSTERITY Trial)

Recruiting at 69 trial locations

Overseen By Reference Study ID Number: WA42985 http://www.roche.com/about_roche/roche_worldwide.htm

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must be taking: IV methylprednisolone

Disqualifiers: CNS SLE, Cancer, Immunodeficiency, others

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: 5

Duration: 52 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests obinutuzumab, a drug targeting lupus nephritis, a kidney inflammation caused by lupus. The goal is to assess the drug's safety and effectiveness, particularly in children with a confirmed diagnosis of active lupus nephritis. Participants are divided into groups, with some receiving the drug and others a placebo (a non-active substance). This trial may suit children with a recent lupus nephritis diagnosis confirmed by a doctor's test. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that obinutuzumab has been tested in people with lupus nephritis, a kidney condition. In these studies, nearly half of the patients who received obinutuzumab showed a noticeable improvement in kidney function, outperforming those who received a placebo, which contains no active medicine.

Regarding safety, clinical trials have generally found obinutuzumab to be well-tolerated, with no major safety issues reported. However, as with any treatment, some individuals might experience side effects. Prospective participants should discuss any concerns with their healthcare provider before joining a trial. ^{1 2 3 4 5}

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

Obinutuzumab is unique because it targets CD20, a protein on the surface of certain immune cells, and depletes these cells, which are thought to contribute to the inflammation and kidney damage seen in lupus nephritis. Unlike standard treatments for lupus nephritis, such as corticosteroids or immunosuppressants like mycophenolate mofetil, obinutuzumab is a monoclonal antibody that offers a more targeted approach. Researchers are excited about obinutuzumab because it has the potential to reduce disease activity more effectively and with fewer side effects than current therapies. Additionally, its administration through intravenous infusions allows for precise dosing and potentially improved patient adherence.

What evidence suggests that obinutuzumab might be an effective treatment for lupus nephritis?

Research has shown that obinutuzumab can help treat lupus nephritis, a kidney condition. In previous studies, about 46.4% of patients who took obinutuzumab experienced full kidney improvement by week 76, compared to 33.1% of those who received a placebo, a treatment with no active medicine. In this trial, participants will receive either open-label or blinded obinutuzumab, or a placebo. Previous studies used obinutuzumab alongside standard therapy, enhancing its effectiveness. These results suggest that obinutuzumab could significantly improve kidney health in people with lupus nephritis. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adolescents aged 12-17 with active Class III or IV Lupus Nephritis (LN) and children aged 5-11 for safety assessment can join this trial. They must have a biopsy confirming LN, meet specific criteria for protein in urine, and have received certain treatments for LN within the last year. Those with isolated Class V disease, severe other diseases, recent cancers, uncontrolled CNS SLE symptoms, drug abuse history or current infections cannot participate.

Inclusion Criteria

My kidney biopsy shows I have Class III or IV lupus nephritis.

I am between 12 and 17 years old.

I am between 5 and 11 years old.

Exclusion Criteria

I do not have severe brain-related lupus symptoms like vision loss, uncontrolled seizures, confusion, or difficulty moving.

I have not had a serious infection or been treated with IV or oral anti-infectives recently.

You have a history of weak immune system or severe blood disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab or placebo infusions on Days 1, 14, Week 24, Week 26, and Week 52

52 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Open-label extension

Evaluation of open label safety and pharmacokinetics in pediatric participants aged 5 to <12

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab

Trial Overview The study is testing Obinutuzumab's effectiveness and safety in treating Lupus Nephritis in adolescents compared to a placebo. It includes medications like Prednisone and Mycophenolate Mofetil as part of treatment regimens. The trial also assesses how the body processes Obinutuzumab in younger children.

How Is the Trial Designed?

Group I: Open-Label Obinutuzumab Experimental Treatment 6 Interventions

Younger participants aged 5 to \<12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.

Group II: Blinded Obinutuzumab Experimental Treatment 6 Interventions

Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).

Group III: Placebo Placebo Group 6 Interventions

Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.

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

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 (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]

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 a meta-analysis of 10 clinical trials involving 2148 subjects, belimumab and obinutuzumab were found to be the most effective biologics for achieving complete remission in lupus nephritis, significantly outperforming placebo and other treatments.

The safety profile of these new biologics is generally good, with belimumab and obinutuzumab showing fewer serious adverse events compared to other treatments, indicating they are safe options for patients when combined with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of novel biologics in the treatment of lupus nephritis based on registered clinical trials: a systematic review and network meta-analysis. Li, F., Cui, W., Huang, G., et al.[2023]

In a study of 9 systemic lupus erythematosus (SLE) patients who did not respond to rituximab, obinutuzumab treatment led to significant reductions in disease activity scores after 6 months, indicating its efficacy in this challenging patient population.

Obinutuzumab also allowed for a reduction in steroid use for many patients, suggesting it may be a safer, steroid-sparing option for managing SLE in those with secondary non-response to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab. Arnold, J., Dass, S., Twigg, S., et al.[2023]

In a study involving 125 patients with proliferative lupus nephritis, obinutuzumab showed a significant improvement in complete renal response at week 104 compared to placebo, with 41% of patients achieving this response versus 23% for the placebo group.

Obinutuzumab was well tolerated, with no increase in serious adverse events or deaths, although non-serious infusion-related reactions were more common, indicating it is a safe option for enhancing renal responses in lupus nephritis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Furie, RA., Aroca, G., Cascino, MD., et al.[2022]

Adding obinutuzumab to standard lupus nephritis therapy significantly reduced the risk of unfavorable kidney outcomes by 60% and LN flares by 57%, based on post hoc analyses of the phase II NOBILITY trial involving 125 patients.

Patients receiving obinutuzumab experienced a slower decline in kidney function, with a notable 4.1 ml/min/1.73 m²/year advantage in eGFR slope, and 38% achieved complete renal response with lower glucocorticoid use compared to 16% in the placebo group at week 76.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kidney Outcomes and Preservation of Kidney Function With Obinutuzumab in Patients With Lupus Nephritis: A Post Hoc Analysis of the NOBILITY Trial. Rovin, BH., Furie, RA., Ross Terres, JA., 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2410965

Efficacy and Safety of Obinutuzumab in Active Lupus ... A complete renal response at week 76 was observed in 46.4% of the patients in the obinutuzumab group and 33.1% of those in the placebo group ( ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39927615/

Efficacy and Safety of Obinutuzumab in Active Lupus ... A complete renal response at week 76 was observed in 46.4% of the patients in the obinutuzumab group and 33.1% of those in the placebo group ( ...

3. roche.com roche.com/media/releases/med-cor-2025-10-20

FDA approves Roche's Gazyva/Gazyvaro for the treatment ... In REGENCY, data showed that nearly half of the participants (46.4%) on Gazyva/Gazyvaro in combination with standard therapy achieved a complete ...

4. lupusresearch.org lupusresearch.org/obinutuzumab-showed-significantly-positive-results-in-published-phase-3-lupus-nephritis-study/

Obinutuzumab Showed Significantly Positive Results in ... Gazyva (obinutuzumab) plus standard therapy demonstrated statistically significant and clinically meaningful improvement in the primary endpoint of complete ...

5. jrheum.org jrheum.org/content/52/Suppl_1/24.1

RESULTS FROM THE REGENCY TRIAL ASSESSING ... Conclusions Obinutuzumab plus standard therapy was more effective than placebo plus standard therapy for achieving CRR, a clinically meaningful ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2468024924033825

WCN25-3676 RESULTS FROM THE REGENCY TRIAL ... Obinutuzumab plus standard therapy was more effective than placebo plus standard therapy for achieving CRR, a clinically meaningful surrogate of kidney function ...