Obinutuzumab + Standard Therapy for Lupus Nephritis

(REGENCY Trial)

Recruiting at 127 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

271 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if adding obinutuzumab to standard treatments is safe and effective for patients with severe kidney inflammation from lupus. It helps the immune system remove harmful cells and has shown better results in kidney health compared to standard treatments alone.

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.

What data supports the effectiveness of the drug Obinutuzumab combined with standard therapy for treating lupus nephritis?

Research shows that Obinutuzumab, when added to standard lupus nephritis treatment, can help preserve kidney function and achieve better kidney remission compared to some other treatments. It was found to be more effective than placebo in achieving overall kidney remission, indicating its potential benefit in treating lupus nephritis. ^{1 2 3 4 5}

Is the combination of Obinutuzumab and standard therapy safe for treating lupus nephritis?

The safety of Obinutuzumab combined with standard therapies for lupus nephritis is generally good, with fewer serious adverse events compared to some other treatments. It showed better safety outcomes in terms of serious infections over two years compared to abatacept. ^{1 3 5 6 7}

What makes the drug Obinutuzumab with Prednisone unique for lupus nephritis?

This treatment is unique because it combines Obinutuzumab, a type of drug that targets and depletes B-cells (a type of immune cell), with standard therapy to potentially preserve kidney function with fewer steroids, which are often used in high doses in other treatments. ^{3 7 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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.

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.

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

Findings from Research

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]

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 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]

References

1. Italy 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. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

New directions in the management of severe lupus nephritis. [2017]

3. United States 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of lupus nephritis: a meta-analysis of clinical trials. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Leflunomide versus cyclophosphamide in the induction treatment of proliferative lupus nephritis in Chinese patients: a randomized trial. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: A multicenter randomized clinical trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Leflunomide for the Treatment of Lupus Nephritis in Chinese Patients: Systematic Review and Meta-Analysis. [2022]

8. China pubmed.ncbi.nlm.nih.gov

[Treatment of proliferative lupus nephritis with leflunomide and steroid: a prospective multi-center controlled clinical trial]. [2018]

9. Italy pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. [2022]