Anifrolumab for Systemic Sclerosis

(DAISY Trial)

Recruiting at 183 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Disqualifiers: Severe cardiopulmonary, Overlap syndromes, Malignancy, 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: 54

306 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called anifrolumab for individuals with systemic sclerosis, a condition that hardens and tightens the skin and connective tissues. The study aims to assess the safety and effectiveness of anifrolumab compared to a placebo (a substance with no active drug) when injected under the skin weekly. Suitable candidates for this trial have had systemic sclerosis for less than six years, with symptoms beyond just Raynaud's phenomenon (a condition affecting blood flow to certain body parts). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

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.

Is there any evidence suggesting that anifrolumab is likely to be safe for humans?

Research shows that anifrolumab is generally safe for people. In earlier studies, some participants experienced side effects. Common ones were mild, such as redness or swelling at the injection site. Some also had headaches or colds, but these side effects were usually not serious.

The FDA has approved anifrolumab for treating lupus, indicating it has been tested and used safely in other patients. However, individual reactions can vary, and rare reactions may occur.

This current study is in a later stage, indicating the treatment has already demonstrated some safety in earlier research. Ongoing trials will provide more information about its safety for people with systemic sclerosis. Always consult a healthcare provider about the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for systemic sclerosis?

Anifrolumab is unique because it specifically targets the type I interferon pathway, which is thought to play a significant role in systemic sclerosis, a condition that currently lacks targeted therapies. Unlike the standard immunosuppressive treatments that broadly dampen the immune system, anifrolumab zeroes in on this particular pathway, potentially offering more precise control of the disease with fewer side effects. Researchers are excited about its subcutaneous delivery method, allowing for easier administration compared to intravenous options, which can be more cumbersome for patients.

What evidence suggests that anifrolumab might be an effective treatment for systemic sclerosis?

Research shows that anifrolumab, a treatment under study in this trial, has potential in managing immune system-related conditions. In studies with patients who have systemic lupus erythematosus (a condition somewhat like systemic sclerosis), anifrolumab significantly improved symptoms. Patients experienced decreased disease activity, and some even achieved remission, where symptoms lessen or disappear. These results suggest that anifrolumab might also help those with systemic sclerosis by targeting similar disease pathways. However, because systemic sclerosis can differ, ongoing studies, including this trial, are necessary to confirm its effectiveness for this condition. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Anifrolumab

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.

How Is the Trial Designed?

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

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

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05925803

NCT05925803 | Determine Effectiveness of Anifrolumab In ... The purpose of this study is to evaluate the efficacy and safety of treatment with subcutaneous anifrolumab versus placebo in adult participants with systemic ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39152751/

DAISY study design and rationale The DAISY study will investigate the efficacy and safety of anifrolumab treatment in a diverse group of patients with systemic sclerosis who currently have ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D3460C00002

Determine effectiveness of Anifrolumab In SYstemic ... The purpose of this study is to evaluate the efficacy and safety of treatment with subcutaneous anifrolumab versus placebo in adult participants with systemic ...

4. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/saphnelo-met-primary-endpoint-in-tulip-sc.html

Saphnelo self-administration TULIP-SC Phase III trial ... Subcutaneous administration of first-in-class biologic Saphnelo demonstrates statistically significant and clinically meaningful reduction ...

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/saphnelo-demonstrates-higher-rates-of-remission-in-patients-with-systemic-lupus-erythematosus-compared-to-standard-therapy-alone-over-4-year-period.html

SAPHNELO® demonstrates higher rates of remission in ... A new post-hoc analysis of the TULIP Phase III program provides evidence across four years that remission is an achievable goal with SAPHNELO.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05925803

NCT05925803 | Determine Effectiveness of Anifrolumab In ... The purpose of this study is to evaluate the efficacy and safety of treatment with subcutaneous anifrolumab versus placebo in adult participants with systemic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12278508/

Post-marketing safety signals of anifrolumab in systemic ... This study provides valuable safety data on the real-world application of anifrolumab, confirming known AEs and revealing additional potential risks.