Litifilimab for Lupus

(TOPAZ-1 Trial)

Not currently recruiting at 258 trial locations

Overseen By Global Biogen Clinical Trial Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Biogen

Must be taking: Antimalarials, Steroids, Immunosuppressants

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

Compensation: Varies

Number of Visits: 26

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called litifilimab for individuals with systemic lupus erythematosus (SLE), a condition where the immune system attacks healthy tissues. Researchers aim to determine if litifilimab can reduce disease activity in those who continue to experience active symptoms despite taking standard medications like steroids and antimalarials. Participants will receive either a high or low dose of litifilimab or a placebo every four weeks for 52 weeks, while continuing their usual treatments. Individuals diagnosed with SLE for at least 24 weeks, who are on stable treatment but still experiencing active symptoms, may be suitable for this study. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

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.

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

Research has shown that litifilimab has been tested for safety in people with systemic lupus erythematosus (SLE). In one study, participants who took litifilimab had fewer swollen joints than those who did not, suggesting the treatment is well-tolerated.

Some participants experienced side effects, but these were usually mild, allowing most to continue the treatment without interruption. This study is in Phase 3, indicating that litifilimab has already passed earlier safety tests in previous studies.

Overall, litifilimab appears safe for people based on the research conducted so far. However, ongoing studies will provide more information about its safety. ^{1 2 3 4 5}

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

Researchers are excited about litifilimab for lupus because it targets a specific protein called BDCA2, which is found on certain immune cells involved in inflammation. This is different from most current lupus treatments, like corticosteroids and immunosuppressants, which broadly suppress the immune system. Litifilimab's targeted approach could mean fewer side effects and better management of lupus symptoms by directly tackling the inflammation at its source. Plus, the treatment is administered subcutaneously, which might offer more convenience compared to some existing therapies that require more frequent or complex dosing.

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

Research shows that litifilimab may help treat systemic lupus erythematosus (SLE), a disease where the immune system mistakenly attacks the body. An earlier study found that people with SLE who took litifilimab had fewer swollen and tender joints than those who took a placebo. This suggests that litifilimab might help reduce joint inflammation, a common problem in SLE. In this trial, participants will receive either a high dose or a low dose of litifilimab, or a placebo. Additionally, litifilimab has been effective in reducing skin problems in related lupus conditions. These findings offer hope that litifilimab could help manage symptoms in people with active SLE. ^{1 2 3 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• BIIB059 (litifilimab)
• Placebo

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37148249/

Litifilimab (BIIB059), a promising investigational drug for ... Litifilimab demonstrated efficacy in a randomized phase II clinical trial as a standalone CLE trial using validated skin-specific outcome ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2118025

Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus ... In a phase 2 trial involving participants with SLE, litifilimab was associated with a greater reduction from baseline in the number of swollen ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04895241

A Study to Learn About the Safety of Litifilimab (BIIB059) ... In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with systemic lupus erythematosus (SLE).

4. lupustherapeutics.org lupustherapeutics.org/new-england-journal-of-medicine-publishes-positive-data-of-litifilimab-in-cutaneous-lupus-erythematosus/

New England Journal of Medicine Publishes Positive Data ... Data showed that the study met its primary endpoint, meaning that litifilimab was more effective than placebo in reducing skin disease activity.

5. investors.biogen.com investors.biogen.com/news-releases/news-release-details/biogen-announces-first-patient-dosed-pivotal-study-litifilimab

Biogen Announces First Patient Dosed in Pivotal Study of ... Global Phase 2/3 AMETHYST study will evaluate the efficacy and safety of litifilimab (BIIB059), as compared to placebo in cutaneous lupus ...

6. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT04895241

Learn About the Safety of Litifilimab (BIIB059) Injections and ... In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with systemic lupus erythematosus ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02847598

NCT02847598 | Study to Evaluate BIIB059 (Litifilimab) in ... The primary purpose of the study is to evaluate the efficacy of BIIB059 (litifilimab) in reducing disease activity in participants with systemic lupus ...