Anifrolumab for Skin Lupus
(LAVENDER Trial)
Recruiting in Palo Alto (17 mi)
+194 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must be taking: Antimalarials
Disqualifiers: Suicidal ideation, Severe SLE, Sjögren's, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This study aims to evaluate the efficacy and safety of subcutaneous (SC) anifrolumab versus placebo in adult participants with cutaneous lupus erythematosus (CLE).
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have an inadequate response or intolerance to antimalarial therapy, which might imply some changes to your current treatment. It's best to discuss this with the trial coordinators.
What data supports the effectiveness of the drug Anifrolumab for treating skin lupus?
Research shows that Anifrolumab, a drug that blocks a specific protein involved in inflammation, has helped patients with skin lupus who did not respond to other treatments. In studies, patients experienced significant improvement in their skin condition after using Anifrolumab.
12345Is anifrolumab safe for humans?
Anifrolumab has been studied for safety in people with systemic lupus erythematosus (SLE), showing a generally similar safety profile to placebo, though with a higher incidence of herpes zoster (shingles) infections. Serious adverse events occurred in 8-16% of patients taking anifrolumab compared to 16-19% with placebo.
26789What makes the drug Anifrolumab unique for treating skin lupus?
Anifrolumab is unique because it specifically targets and blocks the type 1 interferon receptor, which plays a key role in the development of skin lupus. This makes it different from other treatments that do not target this pathway, offering a new option for patients who have not responded to standard therapies.
23689Eligibility Criteria
Adults with chronic or subacute cutaneous lupus erythematosus who haven't responded well to anti-malarial therapy or other medications like topical calcineurin inhibitors, systemic glucocorticoids, or immunosuppressants. They must not have a history of tuberculosis and should test negative for COVID-19. Women must follow local cervical cancer screening guidelines.Inclusion Criteria
Participants should have a COVID-19 negative PCR or antigen test result at Screening
I did not respond well or could not tolerate antimalarial treatment.
CLASI-A total score ≥ 10 points at Screening and confirmed at randomization
+4 more
Exclusion Criteria
My lupus is severe or life-threatening.
Participants not meeting eligibility criteria based on laboratory test results at screening
History of an anaphylactic reaction to human proteins or monoclonal antibodies
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
6 weeks
Treatment
Participants receive either anifrolumab or placebo as a subcutaneous injection
51 weeks
Weekly visits for injections
Open-label extension
Participants receive anifrolumab in an open-label treatment period
28 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
13 weeks
1 follow-up visit
Participant Groups
The trial is testing the effectiveness and safety of Anifrolumab, administered under the skin, compared to a placebo in adults with cutaneous lupus erythematosus. Participants will be randomly assigned to receive either Anifrolumab or a placebo.
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Stage 2: AnifrolumabExperimental Treatment1 Intervention
The participants will receive anifrolumab as a SC injection from Week 0/Day 1 up to and including week 51.
Group II: Stage 1: AnifrolumabExperimental Treatment1 Intervention
The participants will receive anifrolumab as a SC injection from Week 0/Day 1 up to and including week 51.
Group III: Stage 2: PlaceboPlacebo Group1 Intervention
The participant will receive placebo as a SC injection from Week 0/Day 1 to Week 23. From Week 24 the participants will receive anifrolumab up to and including Week 51.
Group IV: Stage 1: PlaceboPlacebo Group1 Intervention
The participant will receive placebo as a SC injection from Week 0/Day 1 to Week 23. From Week 24 the participants will receive anifrolumab up to and including Week 51.
Anifrolumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Saphnelo for:
- Moderate to severe systemic lupus erythematosus (SLE)
🇪🇺 Approved in European Union as Saphnelo for:
- Moderate to severe systemic lupus erythematosus (SLE)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteBloomfield Hills, MI
Research SiteRoanoke, VA
Research SiteToronto, Canada
Research SiteSan Francisco, CA
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
ParexelIndustry Sponsor
References
Rapid Response of Refractory Systemic Lupus Erythematosus Skin Manifestations to Anifrolumab-A Case-Based Review of Clinical Trial Data Suggesting a Domain-Based Therapeutic Approach. [2023]Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, and organ manifestations, such as lupus nephritis (LN) or skin disease, may be refractory to standard treatment. Therefore, new agents are required to allow for a more personalized therapeutic approach. Recently, several new therapies have been approved internationally, including voclosporine for LN and anifrolumab for moderately to severely active SLE. Here, we report a case of SLE with a predominant and refractory cutaneous manifestation despite combination treatment with glucocorticoids, hydroxychloroquine, mycophenolate mofetil, and belimumab, which had been present for more than 12 months. Belimumab was switched to anifrolumab, and the patient responded quickly after two infusions (eight weeks) with a reduction in the Cutaneous Lupus Assessment and Severity Index (CLASI) from 17 to 7. In addition, we review the available clinical trial data for anifrolumab with a focus on cutaneous outcomes. Based on phase II and III clinical trials investigating the intravenous administration, a consistent CLASI improvement was observed at 12 weeks. Interestingly, in a phase II trial of subcutaneous anifrolumab application, CLASI response was not different from placebo at 12 weeks but numerically different at 24 and 52 weeks, respectively. Thus, anifrolumab emerges as an attractive new therapeutic option suggesting a possible domain-based approach.
Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. [2022]Treatment of systemic lupus erythematosus (SLE) currently employs agents with relatively unselective immunosuppressive properties. However, two target-specific biological drugs have been approved: belimumab (anti-B-cell-activating factor/BAFF) and anifrolumab (anti-interferon alpha receptor-1/IFNAR1). Here, we performed a comparative risk-benefit assessment for both drugs based on the role of BAFF and IFNAR1 in host defense and the pathogenesis of SLE and by considering the available data on safety and efficacy. Due to differences in target expression sites, anti-IFNAR1, but not anti-BAFF, might elicit organ-specific effects, consistent with clinical efficacy data. The IFNAR1 is specifically involved in innate and adaptive antiviral immunity in most cells of the body. Consistent with this observation, the available safety data obtained from patients negatively selected for LN and neuropsychiatric SLE, primary immunodeficiencies, splenectomy and chronic HIV, HBV, HCV infections suggest an increased risk for some viral infections such as varicella zoster and perhaps influenza. In contrast, BAFF is mainly involved in adaptive immune responses in lymphoid tissues, thus anti-BAFF therapy modulates SLE activity and prevents SLE flares without interfering with local innate host defense mechanisms and should only marginally affect immune memory to previous pathogen exposures consistent with the available safety data from SLE patients without chronic HIV, HBV or HCV infections. When using belimumab and anifrolumab, careful patient stratification and specific precautions may minimize risks and maximize beneficial treatment effects for patients with SLE.
Anifrolumab for treatment of refractory cutaneous lupus erythematosus. [2022]Cutaneous lupus erythematosus (CLE) is a spectrum of skin changes related to systemic lupus erythematosus (SLE), a family of autoimmunity manifesting characteristic multisystem inflammation and damage. Treatment of CLE continues to evolve, especially for patients with moderate to severe disease. Type 1 interferon (IFN-1) plays a significant role in CLE pathogenesis. Anifrolumab, a fully humanized monoclonal antibody, selectively binds and inhibits the IFN-α receptor 1. Evidence from multiple Phase II and III randomized trials resulted in approval for anifrolumab for treatment of moderate to severe SLE. We present a case series of three patients with refractory CLE significantly improved with anifrolumab. The patients were recruited via clinic interaction and treated with anifrolumab from January 2021 to April 2022. Each patient received at least 12 weeks of therapy. Treatment and follow-up is ongoing. Patients were eligible for the study if they were a patient of the UNC Hospital System with resistant CLE, defined as having received inadequate disease control with standard therapies, including antimalarials, disease-modifying agents and biologics. Outcome measures were improvement in patient-reported symptoms and physician observation of erythema and pigmentary changes. All cases demonstrated significant improvement in disease appearance, cutaneous involvement, and symptomology after treatment with 2 months of anifrolumab infusions. Anifrolumab shows great potential for improving CLE in patients who have failed standard of care and multiple treatment options, including those that have failed belimumab or those who smoke. This report highlights the value of anifrolumab in managing patients with refractory CLE.
Viewpoint on anifrolumab in patients with systemic lupus erythematosus and a high unmet need in clinical practice. [2023]Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterised by unpredictable flares. Many patients with SLE are unable to achieve the recommended treatment goal of remission or the intermediate, yet still clinically beneficial, goal of Lupus Low Disease Activity State (LLDAS) with standard of care (SoC) treatments. LLDAS is an emerging treat-to-target goal in SLE with the aim of reducing organ damage and mortality. A high unmet need remains in SLE and mainstay glucocorticoid treatment is associated with unacceptable toxicity. The recently approved type I interferon receptor antagonist anifrolumab is a new treatment option for this historically underserved patient population. In phase 3 trials, a higher percentage of patients on anifrolumab achieved remission, as defined by the Definition Of Remission In SLE (DORIS), and LLDAS compared with placebo. Real-world clinical experience with anifrolumab use is still limited. Until real-world study results and updated treatment guidelines are available, personal expert clinical experience supported by data may inform clinical decision-making. This viewpoint article discusses four example patient types that could be considered for anifrolumab treatment based on (1) high-risk features early in the disease course, (2) inability to achieve and (3) maintain at least LLDAS, or (4) a desire to reduce or stop SoC. These patients with high unmet need may benefit from the addition of anifrolumab to SoC to achieve or maintain the therapeutic goals of LLDAS or DORIS remission.
Anifrolumab for Moderate and Severe Muco-Cutaneous Lupus Erythematosus: A Monocentric Experience and Review of the Current Literature. [2023]Refractory cutaneous manifestations constitute a significant unmet need in patients with cutaneous lupus (CLE), even in the setting of systemic lupus erythematosus (SLE) with otherwise good control of inflammatory manifestations. Anifrolumab, an anti-interferon I receptor monoclonal antibody has recently been approved for serologically positive SLE with or without CLE, but real-life efficacy and safety data are currently limited. In addition, relatively limited evidence exists about the spectrum of cutaneous manifestations potentially benefitting from anifrolumab treatment and about the optimal clinimetrics to monitor treatment efficacy. While summarising current evidence on the topic in the literature, we report on four patients with SLE and refractory CLE who were successfully treated with anifrolumab. We also describe the potential usefulness and complementarity of the cutaneous lupus activity investigator's global assessment (CLA-IGA) in assessing cutaneous activity in patients treated with anifrolumab.
Evaluation of anifrolumab safety in systemic lupus erythematosus: A meta-analysis and systematic review. [2022]Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and type I interferon plays an important role in its pathogenesis. Anifrolumab is a new strategy for the treatment of systemic lupus erythematosus. It could antagonize the activity of all type 1 interferons by binding with type I interferon receptor subunit 1. The aim of our study was to evaluate the safety of anifrolumab in patients with moderate to severe SLE (excluding patients with active severe lupus nephritis or central nervous system lupus).
Anifrolumab: First Approval. [2022]Anifrolumab (anifrolumab-fnia; Saphnelo™) is a monoclonal antibody antagonist of the type 1 interferon receptor (IFNAR). It is being developed by AstraZeneca (under license from Medarex, now Bristol-Myers Squibb) for the treatment of autoimmune disorders, including systemic lupus erythematosus (SLE) and lupus nephritis, the underlying pathogenesis of which involves type 1 interferon. In July 2021, intravenous anifrolumab was approved in the USA for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy. Anifrolumab (intravenous or subcutaneous) continues to be assessed in clinical studies in SLE in various countries, and the intravenous formulation is under regulatory review in the EU and Japan. This article summarizes the milestones in the development of anifrolumab leading to this first approval for the treatment of moderate to severe SLE.
Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials. [2021]Chronic activation of the type I interferon (IFN) pathway plays a critical role in systemic lupus erythematosus (SLE) pathogenesis. Anifrolumab is a human monoclonal antibody to the type I IFN receptor subunit 1, which blocks the action of type I IFNs. Two phase 3 studies (TULIP-1 and TULIP-2) and a phase 2b study (MUSE) provide substantial evidence for the efficacy and safety of anifrolumab for moderately to severely active SLE. In all three studies, monthly intravenous anifrolumab 300 mg was associated with treatment differences >16% compared with placebo at Week 52 in British Isles Lupus Assessment Group-based Composite Lupus Assessment response rates. The combined data across a range of other clinically significant endpoints (e.g. oral corticosteroid reduction, improved skin disease, flare reduction) further support the efficacy of anifrolumab for SLE treatment. The safety profile of anifrolumab was generally similar across all studies; serious adverse events occurred in 8-16% and 16-19% of patients receiving anifrolumab and placebo, respectively. Herpes zoster incidence was greater with anifrolumab (≤7%) vs placebo (≤2%). Evidence from these clinical trials suggests that in patients with active SLE, anifrolumab is superior to placebo in achieving composite endpoints of disease activity response and oral corticosteroid reduction.
Anifrolumab in systemic lupus erythematosus. [2023]Systemic lupus erythematosus is a complex autoimmune disease with variable disease presentation and progression. Hydroxychloroquine and corticosteroids are first-line therapies. Disease severity and organ system involvement guide escalation of immunomodulatory medications beyond these mainstays. Anifrolumab is a first-in-class global type 1 interferon inhibitor recently approved by the United States Food and Drug Administration (FDA) for systemic lupus erythematosus in addition to standard of care. This article reviews the role of type 1 interferons in lupus pathophysiology and the evidence leading to anifrolumab's approval with particular emphasis on the MUSE, TULIP-1 and TULIP-2 trials. In addition to standard of care, anifrolumab can reduce corticosteroid requirements and reduce lupus disease activity, especially skin and musculoskeletal manifestations, with an acceptable safety profile.