Anifrolumab for Myositis

(JASMINE Trial)

Recruiting at 148 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Prednisone, others

Disqualifiers: Inclusion body myositis, Cancer, HIV, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

240 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this multicenter, randomized, placebo-controlled and double-blind study is to evaluate the efficacy and safety of subcutaneous anifrolumab compared with placebo on the overall disease activity in participants with moderate to severe Idiopathic Inflammatory Myopathies (IIM) \[polymyositis (PM) or dermatomyositis (DM)\] while receiving standard of care (SoC) treatment.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications. In fact, participants must be on a stable dose of treatments like oral prednisone for polymyositis or dermatomyositis.

What data supports the effectiveness of the drug Anifrolumab for treating myositis?

Anifrolumab has been shown to be effective in treating systemic lupus erythematosus (SLE), an autoimmune condition, by targeting the type I interferon receptor, which is involved in the disease process. This suggests it might also help with other autoimmune conditions like myositis, although direct evidence for myositis is not provided. ^{1 2 3 4 5}

Is anifrolumab safe for humans?

Anifrolumab has been studied for safety in patients with systemic lupus erythematosus (SLE), showing some risk of viral infections like varicella zoster (chickenpox) and possibly influenza. It is generally considered safe, but patients should be monitored for these infections. ^{5 6 7 8 9}

How is the drug Anifrolumab unique in treating myositis?

Anifrolumab is unique because it targets the type I interferon receptor, which is involved in autoimmune conditions like systemic lupus erythematosus (SLE). This mechanism of action is different from other treatments for myositis, which may not specifically target this pathway. ^{2 3 5 10 11}

Eligibility Criteria

Adults with moderate to severe Idiopathic Inflammatory Myopathies (IIM), specifically Polymyositis or Dermatomyositis, who are already on standard treatments can join. Details about specific inclusion and exclusion criteria are not provided here.

Inclusion Criteria

My weight is between 40 and 100 kg.

Must have 'probable' or 'definite' diagnosis of PM or DM according to the 2017 ACR/EULAR classification criteria for adult myositis

Moderate or severe disease activity per core set measurements

Exclusion Criteria

Participants with severe muscle damage or permanent weakness due to non-PM or non-DM conditions (i.e., stroke) as per the investigator's opinion

I am at high risk for cancer due to my muscle condition.

I was recently hospitalized or treated for a serious infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous anifrolumab or placebo weekly, added to standard of care, to evaluate efficacy and safety in idiopathic inflammatory myopathies

52 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Anifrolumab

Trial Overview The trial is testing the effectiveness and safety of Anifrolumab, given as a shot under the skin, compared to a placebo. Both will be added to usual care for IIM. It's randomized and double-blind, meaning neither participants nor researchers know who gets what during the study.

Participant Groups

Group I: Anifrolumab (subcutaneous weekly injection) Experimental Treatment 2 Interventions

Anifrolumab subcutaneous injection once weekly

Group II: Placebo (subcutaneous weekly injection) Placebo Group 1 Intervention

Matched placebo control subcutaneous injection once weekly

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 study of six female patients with myositis who did not respond to conventional immunosuppressive therapies, mycophenolate mofetil (MMF) was found to be effective in improving muscle strength and reducing creatine kinase (CK) levels over an average treatment duration of 22.3 months.

Patients experienced a significant reduction in their prednisolone dosage from an average of 13.7 mg to 8.5 mg per day, indicating that MMF may help manage myositis symptoms while allowing for lower doses of corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil treatment in resistant myositis. Pisoni, CN., Cuadrado, MJ., Khamashta, MA., 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]

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]

Serum levels of B cell activating factor (BAFF) were significantly higher in patients with myositis compared to healthy controls, suggesting a potential role in the disease's pathology.

Higher BAFF levels were associated with specific autoantibodies, particularly anti-Jo-1, and correlated with muscle damage markers, indicating that BAFF may serve as a therapeutic target in myositis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Krystufková, O., Vallerskog, T., Helmers, SB., et al.[2009]

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 pooled analysis of 925 patients with moderate to severe systemic lupus erythematosus (SLE), anifrolumab (300 mg monthly) was generally well tolerated over 52 weeks, showing an acceptable safety profile.

While anifrolumab was associated with a higher incidence of herpes zoster and respiratory infections compared to placebo, it also had a lower rate of serious adverse events related to SLE exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of anifrolumab in patients with active SLE: an integrated analysis of phase II and III trials. Tummala, R., Abreu, G., Pineda, L., et al.[2021]

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 6-month clinical trial involving 36 patients with refractory dermatomyositis and polymyositis, tocilizumab was found to be safe and well tolerated, with no significant safety concerns reported.

However, tocilizumab did not show any significant efficacy compared to placebo in improving disease symptoms, as measured by the Total Improvement Score and other secondary outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial of Tocilizumab in the Treatment of Refractory Adult Polymyositis and Dermatomyositis. Oddis, CV., Rockette, HE., Zhu, L., et al.[2022]

In a 52-week phase 2b study involving patients with chronic moderate to severe systemic lupus erythematosus (SLE), the antibody anifrolumab at a dose of 300 mg every 4 weeks was found to be effective and safe, leading to a recommendation for this dosage in future phase 3 studies.

The study revealed that lower doses of anifrolumab (less than 300 mg) would result in rapid drug clearance and suboptimal efficacy, highlighting the importance of the 300 mg dose for achieving better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-response analysis for selection of optimal dosage regimen of anifrolumab in patients with systemic lupus erythematosus. Chia, YL., Santiago, L., Wang, B., et al.[2021]

In a phase 3 trial involving 362 patients with systemic lupus erythematosus, anifrolumab (300 mg) administered monthly showed a significant improvement in patient responses compared to placebo, with 47.8% of patients achieving a BICLA response versus 31.5% for placebo (P = 0.001).

While anifrolumab demonstrated efficacy in reducing disease activity and glucocorticoid use, it was associated with a higher incidence of herpes zoster (7.2%) and bronchitis (12.2%), highlighting the need for monitoring safety alongside its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial of Anifrolumab in Active Systemic Lupus Erythematosus. Morand, EF., Furie, R., Tanaka, Y., et al.[2022]

A commercial ELISA immunoassay demonstrated very good agreement with the reference standard of immunoprecipitation for detecting myositis-specific autoantibodies, with Cohen's κ values ranging from 0.86 to 1, indicating high reliability.

The ELISA method was found to be accurate for detecting key autoantibodies such as anti-synthetase, anti-Mi2, and anti-MDA5, which are important for diagnosing and understanding the prognosis of myositis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ELISA is comparable to immunoprecipitation in the detection of selected myositis-specific autoantibodies in a European population. Loganathan, A., McMorrow, F., Lu, H., et al.[2022]

References

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

Mycophenolate mofetil treatment in resistant myositis. [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. New Zealand pubmed.ncbi.nlm.nih.gov

Anifrolumab: First Approval. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. [2009]

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

Safety profile of anifrolumab in patients with active SLE: an integrated analysis of phase II and III trials. [2021]

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

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

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

Randomized Trial of Tocilizumab in the Treatment of Refractory Adult Polymyositis and Dermatomyositis. [2022]

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

Exposure-response analysis for selection of optimal dosage regimen of anifrolumab in patients with systemic lupus erythematosus. [2021]

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

Trial of Anifrolumab in Active Systemic Lupus Erythematosus. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The use of ELISA is comparable to immunoprecipitation in the detection of selected myositis-specific autoantibodies in a European population. [2022]