Anifrolumab for Lupus

(PRIMULA Lac Trial)

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: AstraZeneca

Must be taking: Anifrolumab

Must not be taking: Investigational compounds, Biologics

Disqualifiers: Lupus nephritis, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

Duration: 4 weeks

16 Participants Needed

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. ^{1 2 3 4 5}

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. ^{2 3 4 6 7}

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. ^{1 2 4 6 7}

Research Team

Darin Brimhall, MD

Principal Investigator

PPD, Las Vegas, US

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

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.

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

Trial Overview The 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

Group I: Anifrolumab Experimental Treatment 1 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)

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

Findings from Research

In a 3-year study involving 218 patients with moderate-to-severe systemic lupus erythematosus (SLE), long-term treatment with anifrolumab showed an acceptable safety profile, with only 6.9% of patients discontinuing due to adverse events.

Patients experienced sustained improvements in SLE disease activity and health-related quality of life, with no new safety concerns identified, indicating that anifrolumab effectively manages SLE over an extended period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open-Label Extension Study. Chatham, WW., Furie, R., Saxena, A., et al.[2021]

Anifrolumab is a monoclonal antibody that targets the type 1 interferon receptor and has been approved in the USA for treating moderate to severe systemic lupus erythematosus (SLE) in adults, marking a significant advancement in autoimmune disorder therapies.

The drug is currently being evaluated in ongoing clinical studies and is under regulatory review in the EU and Japan, indicating its potential for broader use in managing SLE and related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab: First Approval. Deeks, ED.[2022]

In the TULIP-LN trial involving 147 patients with active lupus nephritis, the intensified regimen of anifrolumab (900 mg followed by 300 mg) showed a higher rate of complete renal response at Week 104 compared to the basic regimen and placebo (27.3% vs 18.6% and 17.8%).

The safety profile of anifrolumab remained consistent over two years, with 72% of patients reporting at least one adverse event, but serious adverse events were relatively low, suggesting that anifrolumab is a tolerable treatment option for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. Jayne, D., Rovin, B., Mysler, E., et al.[2023]

Belimumab and anifrolumab are two targeted biological drugs approved for treating systemic lupus erythematosus (SLE), with belimumab primarily affecting adaptive immune responses and anifrolumab potentially causing organ-specific effects due to its action on the IFNAR1 receptor.

Safety data indicate that anifrolumab may increase the risk of certain viral infections, while belimumab appears to have a more favorable safety profile, suggesting that careful patient selection and monitoring are essential to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. Kirou, KA., Dall Era, M., Aranow, C., et al.[2022]

In a phase IIb trial involving 305 patients with moderate-to-severe systemic lupus erythematosus (SLE), anifrolumab significantly improved disease activity compared to placebo, particularly in patients with a high interferon gene signature, with 34.3% of patients on the 300 mg dose achieving a response at week 24.

Anifrolumab's safety profile was generally similar to placebo, but it was associated with a higher incidence of herpes zoster and influenza-like symptoms, indicating a need for monitoring these potential side effects in treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon Inhibition for Lupus with Anifrolumab: Critical Appraisal of the Evidence Leading to FDA Approval. Loncharich, MF., Anderson, CW.[2022]

Anifrolumab, a monoclonal antibody targeting the type I interferon receptor, has shown significant efficacy in treating moderately to severely active systemic lupus erythematosus (SLE), with over 16% improvement compared to placebo in response rates after 52 weeks in phase 3 studies (TULIP-1 and TULIP-2).

The safety profile of anifrolumab is comparable to placebo, although there is a higher incidence of herpes zoster in patients receiving the treatment (up to 7% vs. 2% for placebo), indicating that while effective, monitoring for this specific side effect is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials. Tanaka, Y., Tummala, R.[2021]

Anifrolumab, a treatment for systemic lupus erythematosus (SLE), was found to have a lower incidence of serious adverse events compared to placebo in a meta-analysis of 1160 patients from four randomized controlled trials, indicating good safety.

Common adverse events associated with anifrolumab included upper respiratory infections and herpes zoster, but overall, it is considered a well-tolerated option for patients with moderate to severe SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of anifrolumab safety in systemic lupus erythematosus: A meta-analysis and systematic review. Liu, Z., Cheng, R., Liu, Y.[2022]

References

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

Long-Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open-Label Extension Study. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Anifrolumab: First Approval. [2022]

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

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. [2022]

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

Interferon Inhibition for Lupus with Anifrolumab: Critical Appraisal of the Evidence Leading to FDA Approval. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of anifrolumab safety in systemic lupus erythematosus: A meta-analysis and systematic review. [2022]