Litifilimab for Lupus

(EMERALD Trial)

Recruiting at 553 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

864 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing litifilimab, a medication for people with active systemic lupus erythematosus (SLE). It aims to see if the drug can safely reduce the immune system's attack on the body, helping to manage symptoms and prevent organ damage. Litifilimab has shown promise in reducing the number of swollen and tender joints in SLE patients.

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.

What data supports the effectiveness of the drug litifilimab (BIIB059) for lupus?

Litifilimab has shown promise in treating lupus by targeting specific immune cells that produce substances linked to the disease. In early trials, it improved skin symptoms in patients with lupus, suggesting it could be an effective treatment. ^{1 2 3 4 5}

What is known about the safety of litifilimab (BIIB059) in humans?

Litifilimab has been tested in early-stage clinical trials for lupus, and these studies have shown it to be generally safe for human use, with ongoing evaluations in later-stage trials. ^{1 4 6 7 8}

What makes the drug litifilimab unique for treating lupus?

Litifilimab is unique because it targets a specific protein on plasmacytoid dendritic cells, which are key players in lupus, to reduce the production of certain inflammatory substances. Unlike other treatments, it is a monoclonal antibody that specifically binds to BDCA2, helping to control the disease by inhibiting type I and III interferons, which are involved in lupus inflammation. ^{1 3 4 5 9}

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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]

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]

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]

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]

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]

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

Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. [2020]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Treatment of systemic lupus erythematosus patients with the BAFF antagonist "peptibody" blisibimod (AMG 623/A-623): results from randomized, double-blind phase 1a and phase 1b trials. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Belimumab in Chinese Lupus Patients: A Multicenter, Real-World Observational Study. [2023]

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

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