Litifilimab for Lupus

(EMERALD Trial)

Enrolling by invitation at 600 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

Must not be taking: Investigational drugs

Disqualifiers: Early terminators, Organ-specific lupus, others

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: 47

Duration: 156 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term safety of litifilimab for individuals with systemic lupus erythematosus (SLE), a condition where the immune system attacks the body's tissues. Participants will continue using their usual medications, such as antimalarials and steroids, while receiving litifilimab injections every four weeks for about three years. The main goal is to assess the long-term safety of litifilimab and its effectiveness in managing SLE symptoms. Individuals who participated in earlier studies of litifilimab and completed the treatment period without severe complications are well-suited for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment for SLE.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants will continue to take their standard of care medications, which may include antimalarials, steroids, and immunosuppressants, during the trial.

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

Research has shown that litifilimab has been tested in people with systemic lupus erythematosus (SLE) and shows promise. One study linked litifilimab to a greater reduction in swollen and tender joints compared to a placebo over 24 weeks, suggesting it might help with some lupus symptoms.

Regarding safety, studies have examined how well people tolerate litifilimab. As a Phase 3 trial, it builds on earlier studies that have already checked for major safety concerns. While these earlier studies provide some reassurance about the treatment's safety, researchers are still gathering more data, especially on long-term effects.

Reports so far suggest that litifilimab is generally well-tolerated, but risks remain. Ongoing research aims to better understand any unwanted effects and ensure the treatment is as safe as possible for those with lupus. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about litifilimab for lupus because it offers a novel therapeutic approach by targeting the blood dendritic cell antigen 2 (BDCA2) receptor, which is not addressed by existing treatments. Current standard treatments for lupus often include corticosteroids, antimalarials like hydroxychloroquine, and immunosuppressants, which mainly focus on dampening overall immune response rather than targeting specific pathways. Litifilimab’s mechanism aims to modulate immune activity more precisely, potentially reducing symptoms with fewer side effects. Additionally, litifilimab is administered subcutaneously once every four weeks, which could be more convenient compared to some existing treatments that require more frequent dosing. This precise and potentially more manageable treatment regimen has generated considerable enthusiasm among researchers.

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

Research has shown that litifilimab offers promising results for people with systemic lupus erythematosus (SLE). In one study, litifilimab reduced symptoms like joint swelling more effectively than a placebo. Another study found it was superior to a placebo in reducing skin problems. These findings suggest that litifilimab could help manage SLE by lowering disease activity and improving skin health. This trial will evaluate different doses of litifilimab, with some participants receiving a low dose and others a high dose, to further understand its effects on the immune system and inflammation, which are major issues in lupus. ^{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 with active systemic lupus erythematosus (SLE) who finished one of the parent Phase 3 studies. They must have completed treatment up to Week 48 and attended their last study visit at Week 52.

Inclusion Criteria

I completed a 52-week trial for litifilimab or placebo and attended all required visits.

Exclusion Criteria

I am not using experimental or off-label drugs for lupus.

Early parent Phase 3 studies treatment terminators (participants who discontinued study treatment before Week 52)

Early parent Phase 3 studies terminators (participants who withdrew from study participation and did not complete the 52 week treatment period)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive litifilimab injections every 4 weeks for 156 weeks, continuing their standard of care medications

156 weeks

Up to 47 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• BIIB059 (litifilimab)

Trial Overview The trial is testing the long-term safety and effectiveness of a drug called Litifilimab in people with SLE. It will compare ongoing Litifilimab use against a placebo, looking at disease activity, organ damage prevention, corticosteroid use, quality of life, symptoms impact, lab parameters, and immune response.

How Is the Trial Designed?

Group I: Litifilimab Low Dose Experimental Treatment 2 Interventions

Participants who are receiving background nonbiologic lupus standard of care (SOC) therapy and received litifilimab low dose, subcutaneously (SC), every 4 weeks (Q4W) during the parent Phase 3 studies (i.e. studies 230LE303 \[NCT04895241\] or 230LE304 \[NCT04961567\]) will continue to receive litifilimab low dose, SC, Q4W from Day 1 up to 152 weeks with an additional dose of litifilimab-matching placebo at Week 2. Participants who are receiving background nonbiologic lupus SOC therapy and received litifilimab-matching placebo in the parent Phase 3 studies (i.e. studies 230LE303 \[NCT04895241\] or 230LE304 \[NCT04961567\]) will be randomized to receive litifilimab low dose, SC, Q4W from Day 1 up to 152 weeks with an additional dose at Week 2.

Group II: Litifilimab High Dose Experimental Treatment 2 Interventions

Participants who are receiving background nonbiologic lupus SOC therapy and received litifilimab high dose, SC, Q4W during the parent Phase 3 studies (i.e. studies 230LE303 \[NCT04895241\] or 230LE304 \[NCT04961567\]) will continue to receive litifilimab high dose, SC, Q4W from Day 1 up to 152 weeks with an additional dose of litifilimab-matching placebo at Week 2. Participants who are receiving background nonbiologic lupus SOC therapy and received litifilimab-matching placebo in the parent Phase 3 studies (i.e. studies 230LE303 \[NCT04895241\] or 230LE304 \[NCT04961567\]) will be randomized to receive litifilimab high dose, SC, Q4W from Day 1 up to 152 weeks 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]

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]

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]

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 (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]

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 224 Chinese lupus patients treated with belimumab for an average of 11.7 months, 54.76% achieved a Lupus Low Disease Activity State (LLDAS) and 28.57% attained remission, indicating the drug's effectiveness in managing lupus symptoms.

The treatment was associated with a lower flare rate in patients with mild disease compared to a control group, and while some infections were reported, the overall safety profile supports belimumab's use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Belimumab in Chinese Lupus Patients: A Multicenter, Real-World Observational Study. Sun, F., Wu, H., Wang, Z., et al.[2023]

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.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 ... Larger and longer trials are necessary to determine the effect and safety of litifilimab in patients with cutaneous lupus erythematosus. Notes.