Litifilimab for Systemic Lupus Erythematosus

(AMETHYST LTE Trial)

Recruiting at 50 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

322 Participants Needed

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 cutaneous lupus erythematosus (CLE). The study will focus on participants who have either active subacute CLE or chronic CLE, or both. They may also have systemic lupus erythematosus (SLE). The participants did not respond to antimalarial therapy or had problems with the treatment that made it hard to continue. The study will enroll only those participants who have completed treatment with litifilimab in the parent study, 230LE301. The main objective of the study is learning more about the long-term safety of litifilimab. The main question researchers want to answer is: - How many participants have adverse events and serious adverse events after taking litifilimab? Adverse events are unwanted medical problems that may or may not be caused by the study drug. Researchers will also learn more about the effect of litifilimab on CLE. They will do this by measuring the symptoms of CLE over time using a variety of scoring tools. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), the Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R), and the SELENA-SLEDAI Flare Index (SFI). Researchers will assess the effect litifilimab and CLE has on the quality of life of participants using a group of questionnaires. They will also study how litifilimab affects laboratory tests and how participants' immune systems respond to litifilimab. The study will be done as follows: * The last visit of parent study 230LE301 will be the first visit of study 230LE305. * All participants will receive litifilimab as an injection under the skin once every 4 weeks. Both researchers and participants will know the dose and identity of the study drug. * The treatment period will last up to 104 weeks, or 2 years. * There will be a follow-up safety period that lasts up to 24 weeks. * In total, participants will have up to 33 study visits. * The total study duration for participants will be up to 128 weeks.

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.

What data supports the effectiveness of the drug litifilimab for systemic lupus erythematosus?

Litifilimab has shown promise in early trials for systemic lupus erythematosus (SLE) by targeting plasmacytoid dendritic cells, which are important in the disease. In phase I and II trials, it met primary goals for both systemic and cutaneous lupus, suggesting it may help reduce disease activity. ^{1 2 3 4 5}

Is litifilimab (BIIB059) safe for humans?

Litifilimab has been tested in early-stage trials for lupus, and these studies have shown it to be generally safe for humans, but it is still being evaluated in further trials to confirm its safety. ^{1 2 6 7 8}

What makes the drug litifilimab unique for treating systemic lupus erythematosus?

Litifilimab is unique because it targets plasmacytoid dendritic cells, which are key in producing type I interferons that play a major role in lupus. This drug works by binding to a specific protein on these cells, reducing the production of interferons and other inflammatory substances, which is different from other treatments that may not target this pathway. ^{1 2 9 10 11}

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: BIIB059 Experimental Treatment 1 Intervention

Participants will receive BIIB059 subcutaneously, once every 4 weeks up to Week 100.

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]

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]

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]

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]

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 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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

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

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

Blisibimod for treatment of systemic lupus erythematosus: with trials you become wiser. [2018]

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

Belimumab for systemic lupus erythematosus: a practice-based view. [2013]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study-Joint and Skin (BeRLiSS-JS). [2023]

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

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. [2013]

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

Long-term safety and efficacy of belimumab in Japanese patients with SLE: A 7-year open-label continuation study. [2023]

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

Safety of off-label biologicals in systemic lupus erythematosus. [2015]

9. France pubmed.ncbi.nlm.nih.gov

[Resistant and progressive cutaneous lupus erythematosus treated with belimumab: A retrospective monocentric study]. [2020]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Anifrolumab for treatment of refractory cutaneous lupus erythematosus. [2022]