Litifilimab for Cutaneous Lupus Erythematosus

(AMETHYST Trial)

Recruiting at 304 trial locations

Overseen By US Biogen Clinical Trial Center

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Biogen

Must not be taking: Intralesional corticosteroids, Immunosuppressives

Disqualifiers: Active skin conditions, Mixed connective tissue disease, Severe lupus nephritis, Active neuropsychiatric SLE, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

474 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, litifilimab, for people with cutaneous lupus erythematosus (CLE), a skin condition that causes rashes and sores. The goal is to determine if litifilimab can reduce skin redness and overall disease activity in those who haven't found success with treatments like antimalarial drugs. Participants will receive either the study drug or a placebo (a look-alike with no real medicine) as an injection under the skin. The trial will also assess how the treatment affects quality of life. This trial suits those with active skin symptoms from CLE that haven't improved with antimalarial treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of a potentially effective new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that you cannot use certain treatments like intralesional corticosteroids within 1 week before the study or start new immunosuppressive treatments less than 12 weeks before joining. It's best to discuss your current medications with the study team.

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

Research shows that litifilimab, a drug under study for treating cutaneous lupus erythematosus (CLE), has potential in reducing skin disease activity. In a previous study, litifilimab proved more effective than a placebo in reducing skin disease activity over 16 weeks, suggesting it may help manage CLE symptoms.

Regarding safety, earlier research has examined how well the body tolerates litifilimab. Participants generally handled the drug well, with no major safety issues reported. However, like any medication, some participants experienced side effects, which were usually mild to moderate.

This study combines both early and later testing stages, indicating some confidence in its safety. However, ongoing trials are crucial to fully understand its safety profile. Researchers will closely monitor participants in this trial to quickly address any side effects. ^{1 2 3 4 5}

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

Litifilimab is unique because it targets an immune system protein called BDCA2, which plays a role in the inflammation process linked to cutaneous lupus erythematosus. Most current treatments for this condition, such as corticosteroids and antimalarials like hydroxychloroquine, focus on broadly suppressing the immune response or reducing inflammation. In contrast, litifilimab specifically inhibits BDCA2, potentially offering more precise control over the inflammatory process with fewer side effects. Researchers are excited about litifilimab because it represents a targeted approach that could improve efficacy and safety compared to existing therapies.

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

Research shows that litifilimab may help treat cutaneous lupus erythematosus (CLE), a skin condition. In earlier studies, litifilimab outperformed a placebo in reducing skin disease activity, achieving its main goal. Participants in this trial may receive litifilimab, which has shown promise in reducing skin symptoms and improving the condition for people with CLE. Evidence indicates that litifilimab might be a good option for those who haven't responded well to other treatments. ^{1 2 5 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 people with active skin lupus (SCLE or CCLE) who haven't gotten better after using antimalarial treatments. They need to have a confirmed diagnosis of CLE, active skin symptoms that meet the study's requirements, and a CLASI-A score of 10 or more.

Inclusion Criteria

I have skin symptoms that fit the study's requirements.

My diagnosis of cutaneous lupus erythematosus is confirmed by tissue examination.

I still have a skin lesion from lupus despite taking antimalarial medication.

Exclusion Criteria

I have not used corticosteroids directly on my lesions in the week before screening or during the study.

I have severe kidney inflammation due to lupus.

I haven't started new SLE or CLE treatments in the last 12 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive either litifilimab or placebo as injections under the skin once every 4 weeks during the double-blind treatment period

24 weeks

6 visits (in-person)

Treatment Period 2

All participants receive litifilimab for 28 weeks

28 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Long-Term Extension (optional)

Participants that qualify may join the Long-Term Extension study, 230LE305

What Are the Treatments Tested in This Trial?

Interventions

• BIIB059
• BIIB059 (litifilimab)
• Placebo

Trial Overview The trial tests if BIIB059 (litifilimab) is better than a placebo at reducing skin disease activity in patients with SCLE/CCLE. It measures this by looking at changes in two scores: CLA-IGA-R and CLASI-A. The study also looks at safety, tolerability, and immune response to the drug.

How Is the Trial Designed?

Group I: Part B (Phase 3): Litifilimab Experimental Treatment 1 Intervention

Participants will receive litifilimab SC Q4W from Week 0 to Week 20, with an additional dose of litifilimab at Week 2 during the DBPC treatment period. Following the DBPC treatment period, participants will receive litifilimab during the ETP from Week 24 to Week 48, with an additional dose of litifilimab-matching placebo at Week 26.

Group II: Part A (Phase 2): Litifilimab Experimental Treatment 1 Intervention

Participants will receive litifilimab subcutaneously (SC) once every 4 weeks (Q4W) from Week 0 to Week 20, with an additional dose of litifilimab at Week 2 during the double-blind placebo-controlled (DBPC) treatment period. Following the DBPC treatment period, participants will receive litifilimab during the extended treatment period (ETP) from Week 24 to Week 48, with an additional dose of litifilimab-matching placebo at Week 26.

Group III: Part A (Phase 2): Placebo Placebo Group 1 Intervention

Participants will receive litifilimab-matching placebo SC Q4W from Week 0 to Week 20, with an additional dose of litifilimab-matching placebo at Week 2 during the DBPC treatment period. Following the DBPC treatment period, participants will receive litifilimab during the ETP from Week 24 to Week 48, with an additional dose of litifilimab at Week 26.

Group IV: Part B (Phase 3): Placebo Placebo Group 1 Intervention

Participants will receive litifilimab-matching placebo SC Q4W from Week 0 to Week 20, with an additional dose of litifilimab-matching placebo at Week 2 during the DBPC treatment period. Following the DBPC treatment period, participants will receive litifilimab during the ETP from Week 24 to Week 48, with an additional dose of litifilimab at Week 26.

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

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]

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 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 of 66 patients with cutaneous lupus erythematosus (CLE), the effectiveness of treatment outcomes varied significantly based on the thresholds used to measure improvement, highlighting the importance of selecting appropriate response criteria.

Factors influencing improvement in CLE activity and skin damage were identified, with older age at disease onset linked to better activity improvement, while certain demographics, like African-American race, were associated with poorer outcomes, emphasizing the need for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust measurement of clinical improvement in patients with cutaneous lupus erythematosus. Nanes, BA., Zhu, JL., Chong, BF.[2022]

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]

A significant association was found between proton pump inhibitors (PPIs) and subacute cutaneous lupus erythematosus (SCLE) through analysis of the FDA Adverse Event Reporting System, indicating that PPIs may trigger this autoimmune condition in susceptible individuals.

Discontinuing PPIs led to remission of SCLE symptoms, and reintroducing PPIs caused a recurrence, highlighting the need for healthcare providers to inform patients about this potential side effect and for regulatory bodies to update PPI labels accordingly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-Induced Subacute Cutaneous Lupus Erythematosus Associated with Proton Pump Inhibitors. Aggarwal, N.[2022]

In a study of 7 patients with refractory cutaneous lupus erythematosus (CLE), treatment with anifrolumab led to rapid and significant improvements in disease severity, with the CLASI activity score decreasing from 17 at baseline to 0 by 3 months.

The clinical response to anifrolumab was associated with a reduction in specific interferon-stimulated genes and normalization of intermediate monocytes, suggesting that not all immune pathways need to be suppressed for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers. Carter, LM., Wigston, Z., Laws, P., et al.[2023]

A new core outcome set (COS) for cutaneous lupus erythematosus (CLE) has been proposed, which includes essential domains like skin-specific disease activity, symptoms, and health-related quality of life, aimed at standardizing clinical trials and observational studies.

Recommended physician-reported measures for assessing disease activity include the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and the Cutaneous Lupus Activity Investigator Global Assessment (CLA-IGA), although no single instrument was identified as superior for patient-reported outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a working core outcome set for cutaneous lupus erythematosus: a practical approach to an urgent unmet need. Guo, LN., Perez-Chada, LM., Borucki, R., et al.[2022]

In a meta-analysis of 4 studies involving 4692 patients, belimumab combined with standard therapy significantly improved the SLE Response Index at 52 weeks compared to placebo plus standard therapy, indicating its efficacy in treating systemic lupus erythematosus (SLE).

The safety profile of belimumab was comparable to placebo, as there was no significant difference in the incidence of serious adverse events between the two groups, suggesting that belimumab is a safe addition to standard therapy for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Belimumab Plus Standard Therapy in Patients With Systemic Lupus Erythematosus: A Meta-analysis. Wei, LQ., Liang, YG., Zhao, Y., et al.[2018]

Anifrolumab 300 mg significantly improved treatment responses in patients with active systemic lupus erythematosus (SLE), showing higher BICLA, SRI7, and SRI8 responses compared to placebo in a meta-analysis of three randomized controlled trials involving 459 patients.

While anifrolumab was effective, it also increased the incidence of herpes zoster infections compared to placebo, highlighting a safety concern despite a lower rate of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab for the treatment of active systemic lupus erythematosus: a meta-analysis of randomized controlled trials. Lee, YH., Song, GG.[2021]

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/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 ...

3. 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 ...

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

Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus ... Litifilimab was associated with a greater reduction from baseline in the number of swollen and tender joints than placebo over a period of 24 weeks.

6. 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).

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.