Anifrolumab for Lupus
(PRIMULA Lac Trial)
Recruiting in Palo Alto (17 mi)
Overseen byDarin Brimhall, MD
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: AstraZeneca
Must be taking: Anifrolumab
Must not be taking: Investigational compounds, Biologics
Disqualifiers: Lupus nephritis, Malignancy, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
Prospective Registry Investigating Maternal, Infant, and Lactation Outcomes in Anifrolumab Users (PRIMULA Lac) is a Post Marketing Requirements (PMR) study designed to fulfill the FDA post-marketing requirements. The study will collect data about the presence of anifrolumab in human breast milk and serum (maternal and infant) among lactating individuals who receive anifrolumab therapeutically.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it requires ongoing treatment with anifrolumab. It is best to discuss your current medications with the trial team to ensure they are compatible with the study requirements.
What data supports the effectiveness of the drug Anifrolumab for treating lupus?
Anifrolumab has been shown to be effective in treating moderate to severe systemic lupus erythematosus (SLE), as it targets the type 1 interferon receptor involved in the disease's underlying causes. It was approved in the USA for this use in 2021, and studies have demonstrated its safety and efficacy in reducing disease activity.12345
Is anifrolumab safe for humans?
Anifrolumab has been studied for safety in people with systemic lupus erythematosus (SLE), and the safety profile is generally similar to placebo, though there is a higher risk of certain viral infections like herpes zoster (shingles). Serious side effects occurred in 8-16% of patients taking anifrolumab compared to 16-19% with placebo.23467
How is the drug anifrolumab different from other lupus treatments?
Anifrolumab is unique because it specifically targets and blocks the type 1 interferon receptor, which plays a key role in lupus, unlike other treatments that generally suppress the immune system. This targeted approach may lead to different effects on the body, such as a higher risk of certain viral infections.12467
Eligibility Criteria
This study is for breastfeeding individuals at least 18 years old with moderate/severe Systemic Lupus Erythematosus (SLE), who are on anifrolumab treatment and have been pumping or breastfeeding for at least 4 weeks. Participants must be willing to exclusively breastfeed/pump, use only lanolin nipple cream during sampling, and continue milk feeding throughout the study.Inclusion Criteria
Maternal: Has reached or will reach steady state with anifrolumab by the time of study Day 1
Maternal: Ongoing treatment with anifrolumab
Infant: Birthweight > 10th percentile
See 10 more
Exclusion Criteria
My infant has a notable health issue or significant medical condition.
Maternal: Received any investigational compound or approved biologic or biosimilar within 30 days or 5 half-lives prior to enrollment
I was diagnosed with lupus nephritis in the past year.
See 4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants receive anifrolumab and undergo milk and serum collection at specified timepoints
4 weeks
14 milk collection visits, 3 maternal serum collection visits, 1 infant serum collection visit
Follow-up
Participants are monitored for maternal and infant adverse events and pharmacokinetic analysis
4 weeks
Treatment Details
Interventions
- Anifrolumab (Monoclonal Antibodies)
Trial OverviewThe PRIMULA Lac trial is examining if the lupus medication anifrolumab can be found in human breast milk and blood serum of both mother and infant. It's a post-marketing study required by the FDA to gather more information after the drug has been approved.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: AnifrolumabExperimental Treatment1 Intervention
Lactating individuals 18 years of age or older receiving anifrolumab therapeutically who provide consent to participate will be included in the study. Milk collection will occur at a series of 14 timepoints, 1 pre-dose (spot) and 13 post-dose: Day 1 \[0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, 18-24 hours\], Day 3 \[48 hours, spot\], Day 4 (spot), Day 6 (spot), Day 8 (spot), Day 12 (spot), Day 16 (spot), Day 22 (spot), and Day 29 (prior to next dose, spot). Maternal serum will be collected Day 1 (pre-dose and 0-4 hours post-dose), Day 12, and approximately Day 29 (immediately preceding subsequent dose). Infant serum will be collected on approximately Day 30 following the next dose and after 24 hours of breast feeding.
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 SiteLas Vegas, NV
Loading ...
Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
PPD DEVELOPMENT, LPIndustry Sponsor
References
Long-Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open-Label Extension Study. [2021]To investigate long-term safety and tolerability of anifrolumab, a human monoclonal antibody to the type I interferon (IFN) receptor subunit 1, in patients with moderate-to-severe systemic lupus erythematosus (SLE).
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 in lupus nephritis: results from second-year extension of a randomised phase II trial. [2023]To characterise the safety and efficacy of anifrolumab in active lupus nephritis (LN) through year 2 of the phase II randomised, double-blind Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP)-LN trial (NCT02547922) of 2 anifrolumab dosing regimens versus placebo.
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.
Interferon Inhibition for Lupus with Anifrolumab: Critical Appraisal of the Evidence Leading to FDA Approval. [2022]Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, et al. Anifrolumab, an anti-interferon-α receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol 2017;69:376-86. Objective To assess the efficacy and safety of anifrolumab, a type I interferon (IFN) receptor antagonist, in a phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate-to-severe systemic lupus erythematosus (SLE). Methods Patients (n = 305) were randomized to receive intravenous anifrolumab (300 mg or 1,000 mg) or placebo, in addition to standard therapy, every 4 weeks for 48 weeks. Randomization was stratified by SLE Disease Activity Index 2000 score (
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.
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).