Anifrolumab for Systemic Sclerosis

(DAISY Trial)

Recruiting in Palo Alto (17 mi)

+146 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Disqualifiers: Severe cardiopulmonary, Overlap syndromes, Malignancy, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing anifrolumab, an injectable medication, in adults with systemic sclerosis. The goal is to see if it can reduce immune system attacks to lessen symptoms and prevent further damage. Anifrolumab is a human monoclonal antibody that targets the type I interferon receptor and has been tested in multiple studies for systemic lupus erythematosus (SLE) and other autoimmune diseases.

Do I need to stop my current medications for the trial?

The trial allows participants to continue stable background therapies, including medications like hydroxychloroquine, methotrexate, and others. It does not specify a need to stop current medications.

How is the drug Anifrolumab different from other treatments for systemic sclerosis?

Anifrolumab is unique because it targets the type I interferon receptor, which is a different mechanism of action compared to other treatments for systemic sclerosis. This approach is novel as it specifically blocks the activity of interferons, proteins that play a role in inflammation and autoimmune diseases. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

Adults aged 18-70 with systemic sclerosis, meeting specific criteria and having the condition for less than 6 years. They must have certain severity scores, stable therapies are allowed. Excludes those with overlap syndromes, recent malignancies (except some skin cancers), severe organ diseases, or conditions that might affect study results.

Inclusion Criteria

My daily activities are somewhat limited due to my health.

I have been diagnosed with systemic sclerosis.

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

Exclusion Criteria

Any condition that, in the opinion of the investigator or AstraZeneca, would interfere with the efficacy or safety evaluation of the study intervention or put participant at safety risk

I have no cancer history in the last 5 years, except for treated skin or cervical cancer.

I have had a stem cell or organ transplant.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

1 or more visits (in-person)

Double Blind Treatment

Participants receive once weekly injections of anifrolumab or matching placebo

52 weeks

In-clinic visits at Weeks 0, 1, 4, 8, 16, 24, 36, 48, and 52

Open Label Treatment

All participants receive anifrolumab once weekly

52 weeks

In-clinic visits at Weeks 52, 53, 56, 64, 76, 88, and 104

Safety Follow-up

Participants are monitored for safety after treatment

12 weeks

1 visit (in-person)

Treatment Details

Interventions

• Anifrolumab (Monoclonal Antibodies)

Trial Overview The trial is testing Anifrolumab's effectiveness against a placebo in adults with systemic sclerosis. Participants will receive either the real drug or a placebo without knowing which one they're getting. Some may later get Anifrolumab openly.

Participant Groups

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

Anifrolumab subcutaneous injection once weekly

Group II: matched placebo control (subcutaneous weekly injection) Placebo Group 1 Intervention

matched placebo control subcutaneous injection once weekly

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 302 rheumatoid arthritis patients, adalimumab combined with methotrexate (MTX) significantly improved treatment outcomes compared to placebo, with 57% of patients on 40 mg of adalimumab achieving a 20% improvement in symptoms (ACR20 response) at 12 weeks.

Adalimumab plus MTX was found to be generally safe, with most adverse events being mild to moderate, and no unexpected safety issues reported, making it a viable option for enhancing the quality of life in RA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adalimumab plus methotrexate for the treatment of rheumatoid arthritis: a multi-center randomized, double-blind, placebo-controlled clinical study.]. Huang, F., Zhang, FC., Bao, CD., et al.[2018]

Methotrexate (MTX) is widely used off-label as an immunosuppressant for various chronic inflammatory rheumatic diseases, despite limited controlled study evidence for its efficacy in these cases.

Rheumatologists have significant experience using MTX successfully in daily practice, often to reduce the need for steroids and prevent disease relapses, highlighting its practical effectiveness even in off-label scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current "off label use" of methotrexate for chronic inflammatory rheumatic diseases]. Briem, S., Lorenz, HM.[2021]

In a study involving 4439 rheumatoid arthritis patients, tocilizumab was found to be the most effective treatment compared to olokizumab and sarilumab, achieving the highest American College of Rheumatology 20% (ACR20) response rate.

All three treatments (tocilizumab, sarilumab, and olokizumab) were more effective than adalimumab and showed similar safety profiles, although the placebo had the least adverse events, indicating a need for careful consideration of side effects in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and safety of tocilizumab, sarilumab, and olokizumab in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials. Ho Lee, Y., Gyu Song, G.[2023]

In a 2-year study involving 1197 patients with rheumatoid arthritis who had inadequate response to methotrexate, sarilumab demonstrated a safety profile consistent with IL-6 receptor blockade, with common side effects including neutropenia and upper respiratory infections.

Patients who started treatment with sarilumab at a higher dose of 200 mg every two weeks showed the best radiographic outcomes, while overall disease activity remained stable regardless of the initial treatment after one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes. Genovese, MC., van Adelsberg, J., Fan, C., et al.[2019]

Sarilumab, when combined with methotrexate, significantly improved symptoms and function in patients with moderate-to-severe rheumatoid arthritis, with ACR20 response rates of 58.0% and 66.4% for the 150 mg and 200 mg doses, respectively, compared to 33.4% for placebo after 24 weeks.

The treatment was generally well tolerated, although some patients experienced adverse events such as infections and elevated liver enzymes, which are consistent with the known effects of interleukin-6 signaling blockade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study. Genovese, MC., Fleischmann, R., Kivitz, AJ., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Adalimumab plus methotrexate for the treatment of rheumatoid arthritis: a multi-center randomized, double-blind, placebo-controlled clinical study.]. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

[Current "off label use" of methotrexate for chronic inflammatory rheumatic diseases]. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and safety of tocilizumab, sarilumab, and olokizumab in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials. [2023]

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

Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes. [2019]

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

Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study. [2022]