Obinutuzumab + Standard Therapy for Lupus Nephritis

(REGENCY Trial)

Not currently recruiting at 151 trial locations

Overseen By Reference Study ID Number: CA41705 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Mycophenolate mofetil, Corticosteroids

Must not be taking: Anti-CD20, Cyclophosphamide

Disqualifiers: Pregnancy, Severe renal impairment, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether adding a drug called obinutuzumab to standard lupus nephritis treatment is safe and effective compared to a placebo. Lupus nephritis, a kidney condition caused by lupus, involves specific types of kidney inflammation. Participants will receive either obinutuzumab or a placebo alongside typical lupus treatments like MMF and prednisone (a corticosteroid). Individuals with active lupus nephritis and a urine protein level indicating kidney issues might be suitable for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you have not taken certain medications like anti-CD20 therapy in the last 9 months or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin in the last 2 months before screening.

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

Research has shown that obinutuzumab has been tested in patients with lupus nephritis, a kidney issue related to lupus. One study found that nearly half (46.4%) of the patients receiving obinutuzumab with standard treatment experienced a full kidney response, meaning improved kidney function. This compared to 33.1% of those who received a placebo, which contains no active medicine.

Regarding safety, studies indicate that obinutuzumab is generally well-tolerated. Common side effects may include infusion site reactions, such as redness or swelling, and some individuals might experience flu-like symptoms. Serious side effects are less common but can occur. Testing obinutuzumab in this setting suggests it has a reasonable safety profile for those considering joining the trial. ^{1 2 3 4 5}

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

Researchers are excited about obinutuzumab for lupus nephritis because it offers a fresh approach to tackling the condition. Most treatments for lupus nephritis, like corticosteroids and immunosuppressive drugs, aim to dampen the immune system broadly. However, obinutuzumab is a monoclonal antibody that specifically targets CD20 proteins on B cells, potentially reducing inflammation more precisely and effectively. This targeted action could mean fewer side effects and a better response for patients compared to standard treatments.

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

Research has shown that adding obinutuzumab, a treatment in this trial, to the usual regimen for lupus nephritis is promising. In one study, 46.4% of patients receiving obinutuzumab experienced complete improvement in kidney function, compared to 33.1% of those receiving a placebo. This suggests that obinutuzumab may be more effective than a placebo in improving kidney health for patients with lupus nephritis. The treatment, known as Gazyva, demonstrated significant and meaningful improvements in clinical trials. These findings offer hope for those facing this challenging condition. ^{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?

This trial is for patients with Class III or IV lupus nephritis, as confirmed by a biopsy within the last 6 months. Participants must have significant protein in their urine and can't be pregnant, breastfeeding, or have received certain other treatments recently. They also shouldn't have severe kidney issues requiring dialysis or transplant.

Inclusion Criteria

My kidney biopsy shows I have a specific type of advanced lupus nephritis.

The amount of protein in your urine is equal to or greater than 1 when measured over a 24-hour period.

Other inclusion criteria may apply

Exclusion Criteria

I do not have any severe illnesses that would stop me from joining the trial.

I currently have an active infection or had a major one recently.

I haven't taken specific immune therapies or certain medications in the last 9 months.

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 at baseline and Weeks 2, 24, 26, 50, and 52, along with standard-of-care therapy consisting of MMF and oral prednisone

52 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Open-label extension (optional)

Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Methylprednisolone
• Obinutuzumab
• Prednisone

Trial Overview The study tests Obinutuzumab's effectiveness and safety against a placebo in patients with specific types of lupus nephritis. All participants will receive standard care including MMF and corticosteroids alongside the test drug or placebo.

How Is the Trial Designed?

Group I: Obinutuzumab Experimental Treatment 6 Interventions

Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.

Group II: Placebo Placebo Group 7 Interventions

Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.

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

Approved in United States as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in European Union as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in Canada as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

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

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 clinical trial involving 51 patients with proliferative lupus nephritis, leflunomide (LEF) showed an 80% total response rate and a 40% complete remission rate, comparable to 75% and 25% respectively for IV cyclophosphamide, indicating LEF's efficacy as an induction therapy.

LEF was generally well-tolerated, though some patients experienced adverse events like infections and alopecia, highlighting the need for further research on its long-term safety and effectiveness in maintenance therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of proliferative lupus nephritis with leflunomide and steroid: a prospective multi-center controlled clinical trial]. Cui, TG., Hou, FF., Ni, ZH., et al.[2018]

Over half of patients with Systemic Lupus Erythematosus develop lupus nephritis, which is diagnosed through clinical signs and confirmed by renal biopsy, highlighting the importance of early detection and treatment.

Recent studies suggest that new treatments, such as Obinutuzumab and Belimumab, which target B lymphocytes, along with the calcineurin inhibitor Voclosporin, can improve renal responses in lupus nephritis when used alongside standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The treatment of lupus nephritis, between consolidated strategies and new therapeutic options: a narrative review]. Fontana, F., Alfano, G., Cappelli, G.[2021]

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]

Citations

1. 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 ( ...

2. nejm.org nejm.org/doi/abs/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 ( ...

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 ...