Obinutuzumab for Lupus

(ALLEGORY Trial)

Recruiting at 131 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

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called obinutuzumab in people with active lupus who have specific antibodies in their blood. These patients are already on standard treatments but need more help. The medication works by reducing harmful immune cells that cause inflammation and damage.

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.

What data supports the effectiveness of the drug Obinutuzumab for treating lupus?

Obinutuzumab has shown promise in treating lupus by effectively depleting B cells, which are involved in the disease, and it has been more effective than rituximab in a lupus model. Additionally, it has been used successfully in patients with lupus nephritis to help preserve kidney function. ^{1 2 3 4 5}

Is Obinutuzumab generally safe for humans?

Obinutuzumab has been used in treating certain blood cancers and has shown a manageable safety profile, with common side effects including low white blood cell counts and infusion-related reactions, which are usually mild to moderate. In studies with monkeys, hypersensitivity reactions were noted, but these are rare in humans. ^{1 4 5 6 7}

How is the drug Obinutuzumab unique for treating lupus?

Obinutuzumab is a unique treatment for lupus because it is a type II anti-CD20 monoclonal antibody that targets and depletes B cells, which are involved in the disease process. It is more effective than similar treatments like rituximab in depleting B cells in lupus, potentially leading to better disease management. ^{1 2 3 5 7}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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 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]

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]

References

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

Obinutuzumab: first global approval. [2021]

2. 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]

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

The Type II Anti-CD20 Antibody Obinutuzumab (GA101) Is More Effective Than Rituximab at Depleting B Cells and Treating Disease in a Murine Lupus Model. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab. [2023]

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

Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia. [2018]

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

Hypersensitivity Reactions to Obinutuzumab in Cynomolgus Monkeys and Relevance to Humans. [2018]

7. Italy pubmed.ncbi.nlm.nih.gov

Flare of a mixed cryoglobulinaemic vasculitis after obinutuzumab infusion. [2022]