Litifilimab for Lupus

(TOPAZ-1 Trial)

Recruiting at 209 trial locations

Overseen By Global Biogen Clinical Trial Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Biogen

Must be taking: Antimalarials, Steroids, Immunosuppressants

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with systemic lupus erythematosus (SLE). The study will focus on participants who have active disease and are already taking standard of care medications. These may include antimalarials, steroids, and immunosuppressants. The main objective of the study is to learn about the effect litifilimab has on lowering the activity of the disease. The main question researchers want to answer is: - How many participants have an improvement in their symptoms after 52 weeks of treatment? Researchers will answer this and other questions by measuring the symptoms of SLE over time using a variety of scoring tools. These include the SLE Responder Index (SRI), the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), and the Patient Global Assessment - Visual Analog Scale (PGA-VAS). Researchers will also learn more about the safety of litifilimab. They will study how participants' immune systems respond to litifilimab. Additionally, they will measure the effect litifilimab and SLE have on the quality of life of participants using a group of questionnaires. The study will be done as follows: * After screening, participants will be randomized to receive either a high or low dose of litifilimab, or placebo. A placebo looks like the study drug but contains no real medicine. * All participants will receive either litifilimab or placebo as injections under the skin once every 4 weeks. The treatment period will last 52 weeks. Participants will continue to take their standard of care medications. * Neither the researchers nor the participants will know if the participants are receiving litifilimab or placebo. * There will be a follow-up safety period that lasts up to 24 weeks. * In total, participants will have up to 22 study visits. The total study duration for participants will be up to 80 weeks.

Do I need to stop my current medications for the trial?

No, you will not need to stop your current medications. Participants will continue taking their standard of care medications, such as antimalarials, steroids, and immunosuppressants, during the trial.

What data supports the effectiveness of the drug litifilimab (BIIB059) for treating lupus?

Research shows that litifilimab (BIIB059) targets specific cells involved in lupus, reducing harmful proteins that cause inflammation. Early trials have shown positive results in patients with lupus, suggesting it may help manage the condition. ^{1 2 3 4 5}

What makes the drug litifilimab unique for treating lupus?

Litifilimab is unique because it targets a specific protein on plasmacytoid dendritic cells, which are key players in lupus, to reduce the production of inflammatory substances. This approach is different from other treatments and is particularly promising for cutaneous lupus erythematosus, for which there are no FDA-approved therapies. ^{1 2 6 7 8}

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

Adults diagnosed with systemic lupus erythematosus (SLE) for at least 24 weeks, meeting specific criteria and having active disease despite standard treatments. They must not be on high-dose steroids or have severe kidney issues, uncontrolled heart failure, certain infections like HIV or hepatitis, other skin conditions that could affect assessments, or a history of severe herpes infection.

Inclusion Criteria

I have been on a stable lupus treatment for at least 4 weeks.

I was diagnosed with lupus more than 24 weeks ago and meet the 2019 lupus criteria.

Participant has a modified clinical SLEDAI-2K score ≥ 4 (excluding anti-dsDNA, low complement component 3 (C3) and/or complement component 4 (C4), alopecia, fever, lupus-related headache, and organic brain syndrome) at Screening (adjudicated) and randomization

Exclusion Criteria

I have severe heart failure that is not under control.

I have severe lupus affecting my kidneys or very poor kidney function.

History of severe herpes infection

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a high or low dose of litifilimab or placebo as injections under the skin once every 4 weeks for 52 weeks, while continuing their standard of care medications.

52 weeks

Injections every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Up to 22 study visits in total

Treatment Details

Interventions

• BIIB059 (litifilimab) (Monoclonal Antibodies)
• Placebo (Other)

Trial Overview The trial is testing the effectiveness and safety of BIIB059 (litifilimab) versus placebo in reducing SLE activity while participants continue their usual lupus medications. It aims to show benefits in overall disease control, organ-specific outcomes like joint and skin health, reduced need for steroids, and improved quality of life.

Participant Groups

Group I: Litifilimab Low Dose Experimental Treatment 1 Intervention

Participants who are receiving background nonbiologic lupus SOC therapy will receive low dose of litifilimab, SC Q4W, up to Week 48 with an additional dose at Week 2.

Group II: Litifilimab High Dose Experimental Treatment 1 Intervention

Participants who are receiving background nonbiologic lupus SOC therapy will receive high dose of litifilimab, subcutaneously (SC) every 4 weeks (Q4W), up to Week 48 with an additional dose at Week 2.

Group III: Placebo Placebo Group 1 Intervention

Participants who are receiving background nonbiologic lupus SOC therapy will receive litifilimab-matching placebo, SC Q4W, up to Week 48 with an additional dose at Week 2.

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Findings from Research

Litifilimab (BIIB 059) is a humanized monoclonal antibody that targets BDCA2 on plasmacytoid dendritic cells, effectively inhibiting the production of type I and type III interferons, which are crucial in the pathogenesis of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).

Phase I and II trials (LILAC parts A and B) demonstrated that litifilimab met its primary endpoints in patients with SLE and CLE, and it is now being tested in phase III trials, highlighting its potential as a therapeutic option for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development of litifilimab (BIIB 059) for cutaneous and systemic lupus erythematosus. Cho, YM., Furie, R.[2023]

In a clinical trial involving 54 healthy volunteers and 12 patients with systemic lupus erythematosus (SLE), single doses of BIIB059 demonstrated a favorable safety profile and effective pharmacokinetics, indicating it is safe for use.

BIIB059 effectively reduced inflammatory markers and skin disease activity in SLE patients by targeting plasmacytoid dendritic cells (pDCs), suggesting it could be a promising treatment for SLE, particularly for those with skin symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. Furie, R., Werth, VP., Merola, JF., et al.[2020]

In a comparison of belimumab and anifrolumab for treating systemic lupus erythematosus (SLE), both treatments showed similar efficacy based on the SLE Responder Index (SRI-4) response after 52 weeks, with a slight favor towards belimumab.

The analysis included data from eight trials with a robust methodology, but the uncertainty in the results indicates that further research is needed to identify which specific patient groups might benefit more from either treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab versus anifrolumab in adults with systemic lupus erythematosus: an indirect comparison of clinical response at 52 weeks. Neupane, B., Shukla, P., Slim, M., et al.[2023]

In a Phase 2b clinical trial involving 547 patients with systemic lupus erythematosus (SLE), the highest dose of blisibimod (200 mg once-weekly) showed statistically significant improvements in disease response rates compared to placebo, particularly in patients with severe disease.

Blisibimod was found to be safe, with no significant differences in serious adverse events or infections compared to placebo, indicating it could be a viable treatment option for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study. Furie, RA., Leon, G., Thomas, M., et al.[2022]

In a phase III trial with 819 patients, belimumab at 10 mg/kg significantly improved the SLE Responder Index response rate at week 52 compared to placebo (43.2% vs. 33.5%), indicating its efficacy in reducing disease activity in systemic lupus erythematosus (SLE).

Belimumab was generally well tolerated, with serious adverse events being comparable across treatment groups, suggesting that it is a safe addition to standard therapy for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Furie, R., Petri, M., Zamani, O., et al.[2022]

Litifilimab, a monoclonal antibody targeting BDCA2, showed significant efficacy in treating cutaneous lupus erythematosus (CLE) in a phase II randomized controlled trial, marking it as the first successful targeted therapy for this condition.

If approved by the FDA, litifilimab could transform the management of severe and refractory CLE, addressing a critical gap in available treatments for this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Litifilimab (BIIB059), a promising investigational drug for cutaneous lupus erythematosus. Cho, SK., Vazquez, T., Werth, VP.[2023]

In a phase IIb study involving 431 adults with moderate to severe systemic lupus erythematosus (SLE), sifalimumab showed significant efficacy, with higher response rates compared to placebo (up to 59.8% for the highest dose) at week 52.

While sifalimumab demonstrated promising improvements in various measures of disease activity, it was associated with a slightly higher incidence of serious adverse events and more frequent herpes zoster infections compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Khamashta, M., Merrill, JT., Werth, VP., et al.[2022]

In a post hoc analysis of a phase IIb trial involving patients with moderate to severe systemic lupus erythematosus (SLE), anifrolumab 300 mg every 4 weeks significantly improved rash and arthritis symptoms compared to placebo, with notable improvements in various assessment scales.

The treatment was particularly effective in patients with a high type I interferon gene signature, showing substantial resolution of rash and improvement in arthritis, while results in patients with a low gene signature were less pronounced, indicating a need for further research in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus. Merrill, JT., Furie, R., Werth, VP., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

The development of litifilimab (BIIB 059) for cutaneous and systemic lupus erythematosus. [2023]

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

Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Belimumab versus anifrolumab in adults with systemic lupus erythematosus: an indirect comparison of clinical response at 52 weeks. [2023]

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

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study. [2022]

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

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Litifilimab (BIIB059), a promising investigational drug for cutaneous lupus erythematosus. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus. [2022]