Obinutuzumab for Lupus

(ALLEGORY Trial)

Not currently recruiting at 147 trial locations

Overseen By Reference Study ID Number: CA42750 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Oral corticosteroids, antimalarials

Must not be taking: Anti-CD20, anti-CD19

Disqualifiers: Pregnancy, Renal disease, Infection, 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

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: 4

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests obinutuzumab, a new treatment for people with active systemic lupus erythematosus (SLE), a condition where the immune system attacks the body. The researchers aim to determine if obinutuzumab is more effective and safe than a placebo (a dummy treatment) when used alongside standard lupus treatments. Participants should have SLE with high disease activity and be on one or more standard treatments, such as steroids or antimalarials. 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 your current medications, but it mentions that participants should be on stable doses of standard therapies for lupus, like oral corticosteroids, antimalarials, or conventional immunosuppressants. It's best to discuss your specific medications with the trial team.

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, yielding promising safety results. In one study, patients experienced noticeable symptom improvements, and the treatment was generally well-tolerated.

Another report found that by 76 weeks, 46.4% of patients taking obinutuzumab experienced significant benefits, compared to only 33.1% in the placebo group. This suggests that obinutuzumab could be a safe and effective option for treating lupus, as it seems to help more people without causing many serious side effects.

Overall, the evidence so far supports the idea that obinutuzumab is safe for use in people with lupus. ^{1 2 3 4 5}

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

Unlike the standard treatments for lupus, which typically involve corticosteroids and immunosuppressants, Obinutuzumab is a monoclonal antibody that targets the CD20 protein on B cells. This action helps reduce the number of B cells, which play a role in the autoimmune response seen in lupus. Researchers are excited because this targeted approach could offer a more precise way to manage lupus, potentially leading to fewer side effects and better disease control compared to current therapies.

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

Research has shown that obinutuzumab offers promising results for treating systemic lupus erythematosus (SLE). In a previous study, patients who received obinutuzumab experienced significant improvements, with many achieving complete recovery of kidney function by week 52. The treatment also removed certain immune cells called B cells, which play a role in lupus. Another study found that all patients treated with obinutuzumab showed improvements in symptoms, such as reduced protein in their urine and better scores on a test measuring lupus activity. In this trial, participants will receive either obinutuzumab or a placebo. These findings suggest that obinutuzumab could effectively manage lupus symptoms. ^{1 2 3 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 people with active, autoantibody-positive systemic lupus erythematosus (SLE) who have high disease activity despite standard treatments. Participants must meet specific criteria including low complement levels and positive ANA or anti-dsDNA/anti-Sm antibodies. They should not have severe kidney issues related to lupus, be pregnant or breastfeeding, or have used certain excluded therapies recently.

Inclusion Criteria

My lupus is highly active, with a SLEDAI score of 8 or more and a PGA score of 1 or more.

I am currently taking medication for lupus at a stable dose.

The Medical Monitor may be consulted if there are any questions related to eligibility criteria

Exclusion Criteria

I haven't taken specific immune therapies or certain medications in the months before my screening.

Pregnancy or breastfeeding

Other exclusion criteria may apply

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 Day 1 and at Weeks 2, 24, and 26

52 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab

Trial Overview The study tests the effectiveness and safety of Obinutuzumab compared to a placebo in SLE patients on standard care. It's a parallel-group, double-blind trial meaning neither participants nor researchers know who gets the real drug versus placebo during the study.

How Is the Trial Designed?

Group I: Obinutuzumab Experimental Treatment 4 Interventions

Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.

Group II: Placebo Placebo Group 4 Interventions

Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.

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

Published Research Related to This Trial

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 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]

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 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]

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]

Citations

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

Efficacy and Safety of Obinutuzumab in Active Lupus ... In that trial, obinutuzumab led to clinically meaningful improvements in the percentage of patients with a complete renal response at weeks 52, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35266512/

Efficacy and safety of obinutuzumab in systemic lupus ... After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays.

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

FDA approves Roche's Gazyva/Gazyvaro for the treatment ... A study to evaluate the efficacy and safety of obinutuzumab in participants with systemic lupus erythematosus (ALLEGORY). [Internet; cited ...

4. academic.oup.com academic.oup.com/rheumatology/article/64/Supplement_3/keaf142.189/8114984

P149 Evaluating outcomes for patients with systemic lupus ... All the patients in our study had clinical and biochemical benefit from obinutuzumab, evidenced by improvement in SLEDAI scores, proteinuria and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04963296

NCT04963296 | A Study to Evaluate the Efficacy and ... This parallel-group, double-blind, placebo-controlled study will evaluate the efficacy and safety of obinutuzumab versus placebo in participants with active ...

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

RESULTS FROM THE REGENCY TRIAL ASSESSING ... At Week 76, 46.4% of patients in the obinutuzumab group and 33.1% in the placebo group achieved CRR (adjusted difference, 13.4%; 95% CI, 2.0% to ...

7. england.nhs.uk england.nhs.uk/wp-content/uploads/2023/11/2121-evidence-review-obinutuzumab.pdf

Evidence review Obinutuzumab for systemic lupus ... This evidence review aims to examine the clinical effectiveness, safety and cost effectiveness of obinutuzumab compared with immunosuppressant therapies in ...