Litifilimab for Systemic Lupus Erythematosus

(AMETHYST LTE Trial)

Enrolling by invitation at 92 trial locations

Overseen By Global Biogen Clinical Trial Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Biogen

Must be taking: Litifilimab

Disqualifiers: Early terminators, Other medical conditions

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 33

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety of a drug called litifilimab (also known as BIIB059) for individuals with cutaneous lupus erythematosus (CLE), a skin condition that can occur with systemic lupus erythematosus (SLE). Researchers focus on participants with active or chronic CLE that has not improved with antimalarial treatment. Participants should have completed treatment in a previous study with litifilimab. The trial aims to monitor any unwanted side effects and assess how the drug affects CLE symptoms and overall quality of life over time. Participants will receive the drug through regular injections, with the study lasting up to 128 weeks. 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 information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that litifilimab is likely to be safe for humans?

Research shows that litifilimab (also called BIIB059) has been studied for its safety in people with lupus-related conditions. Previous studies found that litifilimab was generally well-tolerated. Some participants experienced mild side effects, such as headaches and injection site reactions. The studies reviewed reported no unexpected, serious side effects directly linked to the drug. This suggests that while some side effects can occur, they are usually not severe. Researchers are currently testing the drug further to ensure its safety for long-term use in treating cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lupus?

Unlike the standard treatments for systemic lupus erythematosus, which often involve immunosuppressants and corticosteroids, BIIB059 (litifilimab) acts on a different target. It specifically targets BDCA2, a receptor on plasmacytoid dendritic cells, which plays a crucial role in the inflammatory process of lupus. This targeted approach has the potential to reduce inflammation more precisely and with potentially fewer side effects. Researchers are excited about BIIB059 because it represents a novel mechanism of action that could offer a more effective and safer alternative for lupus patients.

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

Research shows that litifilimab, the investigational treatment in this trial, may help treat cutaneous lupus erythematosus (CLE), a skin condition. An earlier study found that litifilimab reduced skin disease activity in people with CLE. Another study showed that litifilimab, particularly at a 450 mg dose, decreased the number of swollen and tender joints in people with systemic lupus erythematosus (SLE). These findings suggest that litifilimab could manage symptoms in people with CLE and possibly those with both CLE and SLE. The evidence so far supports its potential effectiveness for these conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for adults who finished the parent study (230LE301) with active subacute or chronic cutaneous lupus erythematosus, and are not responding well to antimalarial therapy. They should understand the study's risks, give informed consent, and allow use of their health information. Those with new medical issues or who left the earlier study early can't join.

Inclusion Criteria

I understand the study's risks and goals and agree to share my health information.

I completed a specific study treatment and attended all required visits.

Exclusion Criteria

Participants who have developed any other medical diseases, conditions, or abnormalities, rendering their participation in the long-term extension (LTE) study unsuitable in the opinion of the Investigator.

You were part of the earlier part of the study but did not finish it before Week 52.

If you stopped taking the study medication before 48 weeks in a previous related study, you cannot participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive litifilimab as an injection under the skin once every 4 weeks

104 weeks

Up to 33 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BIIB059 (litifilimab)

Trial Overview The trial tests long-term safety and effectiveness of BIIB059 (litifilimab) in patients from a previous study. It looks at how litifilimab affects disease activity over time, prevents damage and flares, impacts steroid use, quality of life, lab parameters, immune response to treatment, and drug levels in the body.

How Is the Trial Designed?

Group I: BIIB059 Experimental Treatment 1 Intervention

Participants will receive BIIB059 (litifilimab) subcutaneously (SC), once every 4 weeks up to Week 100 in the LTE period. Following the 2 year long-term extension (LTE) period, participants in the USA will receive BIIB059 (litifilimab), once every 4 weeks up to Week 256.

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 study of 7 patients with resistant cutaneous lupus erythematosus (CLE), 83% showed significant clinical improvement after 6 to 12 months of treatment with belimumab, with one patient achieving complete response and four achieving partial responses.

Belimumab was well-tolerated, leading to the discontinuation of oral corticosteroids in all patients, and only one serious adverse event (bacteremia) was reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Resistant and progressive cutaneous lupus erythematosus treated with belimumab: A retrospective monocentric study]. Dresco, F., Puzenat, E., Delobeau, M., et al.[2020]

In a study involving 364 patients with systemic lupus erythematosus (SLE), long-term treatment with belimumab combined with standard therapy demonstrated a stable or declining incidence of adverse events over 4 years, indicating a favorable safety profile.

The most common side effects were mild, such as arthralgia and upper respiratory infections, and serious infusion reactions were rare, suggesting that belimumab can be safely administered for extended periods in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Merrill, JT., Ginzler, EM., Wallace, DJ., et al.[2013]

In a long-term study of 71 Japanese patients with systemic lupus erythematosus (SLE), belimumab demonstrated a favorable safety profile, with 98.6% experiencing adverse events, but only 11.3% experiencing severe SLE flares over a treatment period of up to 7 years.

The efficacy of belimumab improved over time, with the SLE Responder Index (SRI-4) response rate increasing from 40.9% at Year 1 to 84.6% by Year 7, while the use of corticosteroids and immunosuppressants decreased, indicating sustained treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of belimumab in Japanese patients with SLE: A 7-year open-label continuation study. Tanaka, Y., Curtis, P., DeRose, K., et al.[2023]

Rituximab has a manageable adverse event profile in systemic lupus erythematosus (SLE), while data on other off-label biologicals is limited, indicating a need for careful consideration of safety when using these treatments.

Anti-TNF antibodies can induce SLE-specific autoantibodies, but these were not linked to disease flares, although the risk of severe infections remains a significant concern, especially when combined with glucocorticoids or immunosuppressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of off-label biologicals in systemic lupus erythematosus. Aringer, M., Smolen, JS.[2015]

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]

Blisibimod is a highly potent inhibitor of B cell activating factor (BAFF) and is currently being evaluated for its efficacy and safety in treating systemic lupus erythematosus (SLE) in clinical trials, including the ongoing phase 3 CHABLIS-SC1 trial.

The unique tetravalent 'peptibody' structure of blisibimod may enhance its effectiveness, and its targeted approach towards specific 'responder populations' suggests it could become a significant treatment option for both SLE and IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blisibimod for treatment of systemic lupus erythematosus: with trials you become wiser. Scheinberg, MA., Hislop, CM., Martin, RS.[2018]

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]

Anifrolumab, a monoclonal antibody that inhibits the IFN-α receptor 1, has shown significant improvement in patients with refractory cutaneous lupus erythematosus (CLE) after at least 12 weeks of treatment, as evidenced by a case series of three patients.

All three patients, who had not responded adequately to standard therapies, reported improvements in symptoms and skin appearance, indicating that anifrolumab may be a promising option for those with moderate to severe CLE who have failed other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab for treatment of refractory cutaneous lupus erythematosus. Blum, FR., Sampath, AJ., Foulke, GT.[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. clinicaltrials.gov clinicaltrials.gov/study/NCT04895241

NCT04895241 | A Study to Learn About the Safety of ... These trials gather additional information about a drug's safety, efficacy, or optimal use. ... of studies listed on the Search Results page. You can sort by ...

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

Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus ... Litifilimab administered at a dose of 450 mg was associated with a greater decrease from baseline in the number of swollen and tender joints ...

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

New England Journal of Medicine Publishes Positive Data ... The Phase 2 LILAC study showed that the investigational litifilimab (BIIB059) lessened skin disease activity in cutaneous lupus erythematosus.

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.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 ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2118024

Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous ... Treatment with litifilimab was superior to placebo with regard to a measure of skin disease activity over a period of 16 weeks.