Anifrolumab for Lupus

(BLOSSOM Trial)

Recruiting at 82 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Cytotoxic B-cell depleters

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

A Study to evaluate the PK, PD, efficacy, and safety of Anifrolumab in children with moderate to severe active SLE

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, if you have used certain treatments like Anifrolumab or B-cell depleting therapies recently, you may not be eligible to participate.

What data supports the effectiveness of the drug Anifrolumab for lupus?

Anifrolumab has been shown to be effective in treating systemic lupus erythematosus (SLE), a condition where the immune system attacks the body's own tissues, and lupus nephritis, a kidney inflammation caused by lupus. It works by blocking a specific protein involved in the immune response, and has been approved in the USA for adults with moderate to severe SLE who are already on standard therapy. ^{1 2 3 4 5}

Is Anifrolumab safe for humans?

Anifrolumab has been studied for safety in people with systemic lupus erythematosus (SLE). In clinical trials, serious side effects were reported in 8-16% of patients taking Anifrolumab, compared to 16-19% of those taking a placebo. However, there was a higher incidence of herpes zoster (shingles) in patients taking Anifrolumab (up to 7%) compared to those on placebo (up to 2%). ^{3 4 5 6 7}

What makes the drug Anifrolumab unique for treating lupus?

Anifrolumab is unique because it is a monoclonal antibody that specifically targets and blocks the type I interferon receptor, which plays a key role in the development of systemic lupus erythematosus (SLE). This mechanism of action is different from other lupus treatments, and it has shown effectiveness in reducing disease activity and the need for oral corticosteroids in clinical trials. ^{3 4 6 8 9}

Eligibility Criteria

This trial is for children with moderate to severe active Systemic Lupus Erythematosus (SLE). Participants need consent from a parent or guardian, must meet specific SLE criteria, have no signs of active tuberculosis (TB), and girls able to have babies must not be pregnant and agree to use birth control. A negative COVID-19 test is also required.

Inclusion Criteria

I am a woman who can have children and my pregnancy test was negative.

I am committed to using birth control as required.

I have been diagnosed with lupus according to the 2019 EULAR/ACR criteria.

Exclusion Criteria

I have previously been treated with Anifrolumab.

I have active hepatitis B, hepatitis C, or a severe case of Herpes Zoster.

Any positive result on Screening for human immunodeficiency virus

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Part A - Pharmacokinetic Period

A single-blind, placebo-controlled, randomised pharmacokinetic period

4 weeks

Weekly visits for infusion and monitoring

Part B - Safety/Efficacy Period

Double-blind, placebo-controlled, randomised safety and efficacy period

48-52 weeks

Monthly visits for infusion and assessments

Part C - Open-label Extension

Participants may continue treatment in an open-label extension

52 weeks

Monthly visits for infusion and assessments

Part D - Safety Follow-up

Participants are monitored for safety 12 weeks post last dose

12 weeks

One safety visit

Treatment Details

Interventions

• Anifrolumab
• Placebo

Trial Overview The study tests the effectiveness and safety of Anifrolumab given through an IV compared to a placebo in treating pediatric SLE. It will assess how the drug moves through and affects the body, as well as its ability to improve symptoms.

Participant Groups

Group I: Anifrolumab Experimental Treatment 1 Intervention

Randomized participants will receive a single dose of Anifrolumab via IV infusion every 4 weeks

Group II: Placebo Placebo Group 1 Intervention

Randomized participants will receive matching placebo via IV infusion

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

Findings from Research

In a phase II study involving 147 patients with active lupus nephritis, the primary endpoint of improved urine protein-creatinine ratio was not met for anifrolumab compared to placebo, indicating limited efficacy in this measure.

However, the intensified regimen of anifrolumab showed numerical improvements in secondary outcomes, such as complete renal response and sustained glucocorticoid reductions, although there was a higher incidence of herpes zoster in the anifrolumab groups compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Jayne, D., Rovin, B., Mysler, EF., et al.[2022]

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]

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]

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]

Anifrolumab demonstrated a high retention rate of 89.7% at 26 weeks in patients with systemic lupus erythematosus (SLE), indicating its potential as a long-term treatment option.

In patients experiencing minor flares, anifrolumab significantly reduced glucocorticoid (GC) doses and disease activity (measured by the SELENA-SLEDAI score) compared to standard care, suggesting it may effectively manage SLE without increasing GC use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry. Miyazaki, Y., Funada, M., Nakayamada, S., et al.[2023]

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]

In a long-term extension study involving patients with systemic lupus erythematosus (SLE), anifrolumab 300 mg showed a favorable safety profile, with lower rates of serious adverse events (SAEs) compared to placebo (8.5 vs 11.2 per 100 patient-years).

Anifrolumab also led to greater improvements in disease activity and reduced glucocorticoid use compared to placebo, supporting its efficacy and favorable benefit-risk profile for treating moderate-to-severe SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. Kalunian, KC., Furie, R., Morand, EF., et al.[2023]

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]

In a post hoc analysis of a phase IIb trial involving patients with moderate to severe systemic lupus erythematosus (SLE), anifrolumab 300 mg every 4 weeks significantly improved rash and arthritis symptoms compared to placebo, with notable improvements in various assessment scales.

The treatment was particularly effective in patients with a high type I interferon gene signature, showing substantial resolution of rash and improvement in arthritis, while results in patients with a low gene signature were less pronounced, indicating a need for further research in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus. Merrill, JT., Furie, R., Werth, VP., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. [2022]

2. 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]

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

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

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

Anifrolumab: First Approval. [2022]

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

Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry. [2023]

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

A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. [2023]

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

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

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

Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus. [2022]