Determine effectiveness of Anifrolumab In SYstemic sclerosis (DAISY) - DAISY

Study identifier:D3460C00002

ClinicalTrials.gov identifier:NCT05925803

EudraCT identifier:N/A

CTIS identifier:2022-502142-26-00

Recruiting

Official Title

A Multicenter, Randomized, Parallel-group, Double-blind,Two-arm Phase III Study to Evaluate the Safety and Efficacy of Anifrolumab Compared with Placebo in Male and Female Participants 18 to 70 Years of Age Inclusive with Systemic Sclerosis

Medical condition

Systemic Sclerosis, Scleroderma

Phase

Phase 3

Healthy volunteers

Study drug

Placebo (blinded)

Sex

All

Estimated Enrollment

306

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 08 Nov 2023

Estimated Primary Completion Date: 09 Oct 2026

Estimated Study Completion Date: 31 Dec 2027

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2023 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1) Adult patients from 18 to 70 years of age inclusive
2) Systemic sclerosis according to 2013 ACR/EULAR classification criteria
3) Limited or diffuse cutaneous subsets
4) Systemic sclerosis disease duration within 6 years from first non-Raynaud’s phenomenon manifestation
5) Either HAQ-DI score ≥ 0.25 points or PtGA score ≥ 3 points
6) mRSS > 10 with early disease or rapid progression as defined by the protocol
7) mRSS ≥ 15 with disease duration ≥ 18 months and active disease as defined by the protocol
8) Stable background therapies can be used including hydroxychloroquine, methotrexate, azathioprine, mycophenolate mofetil, mycophenolic sodium, mycophenolic acid, oral glucocorticoids or tacrolimus
9) Women of childbearing potential with a negative urine pregnancy test
10) Uninvolved skin at injection sites

Exclusion Criteria

1) Anticentromere antibody seropositivity on central laboratory
2) Severe cardiopulmonary disease as defined by the protocol
3) History of systemic sclerosis renal crisis within past 12 months (estimated glomerular filtration rate(eGFR) < 45 mL/min)
4) Overlap syndromes, systemic lupus erythematosus with anti-double-stranded deoxyribonucleic acid antibody seropositivity or anti-citrullinated protein antibodies-positive rheumatoid arthritis, or SSc mimics (eg, scleromyxedema, eosinophilic fasciitis)
5) History of, or current, any other inflammatory diseases, eg, inflammatory bowel disease, skin disease, that, in the opinion of the investigator, could interfere with efficacy and safety assessments or require immunomodulatory therapy
6) Evidence of moderately severe concurrent nervous system, renal, endocrine, hepatic (eg, underlying chronic liver disease [Child Pugh A, B, C hepatic impairment]), or gastrointestinal disease (eg, clinical signs of malabsorption or needing parenteral nutrition) not related to SSc, as determined by the investigator
7) Hematopoietic stem cell transplantation or solid organ/limb transplantation
8) Any severe case of Herpes Zoster infection as defined by the protocol
9) Known malignancy or a history of malignancy within 5 years, with exception of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
10) Major surgery within 8 weeks prior to and/or during study enrollment
11) Known active current or history of recurrent infections
12) Severe cardiopulmonary disease
13) 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

This is a multicenter, randomized, double-blind, placebo-controlled, Phase III study to evaluate the efficacy and safety of anifrolumab in the treatment of adult participants with Systemic Sclerosis (SSc) who may be taking one or a combination of protocol-specified standard therapies. The use of one of the following standard immunosuppressant therapies is permitted at a stable dose, but not mandated: hydroxychloroquine, mycophenolate mofetil (MMF), mycophenolic acid or mycophenolate sodium (MPA), methotrexate, azathioprine, tacrolimus, and oral glucocorticoids. MMF or MPA, azathioprine, and methotrexate may be used in combination with hydroxychloroquine and/or low-dose oral glucocorticoids [≤ 10 mg/day]. Approximately 306 eligible participants will be randomized in a 1:1 ratio to receive either 120 mg anifrolumab (or matching placebo) given subcutaneously once weekly for 52 weeks. The study will be stratified by the following factors: • Interstitial lung disease (ILD) (yes, no) at Week 0 (Day1); • MMF or MPA use (yes ,no) at Week 0 (Day 1); and • Disease duration, defined as the time from the first non-Raynaud’s symptom attributable to SSc (<18 months, ≥ 18 months) at Week 0 (Day 1) Study treatment will be administered subcutaneously via an accessorized prefilled syringe by study staff or by the participant or carer, either in the clinic or at home, with most doses being administered at home. The study consists of 4 periods: a 6-week screening period, a 52-week, double-blind, placebo-controlled period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. There are a total of 16 study visits with most visits in the treatment period occurring every 8 to 12 weeks. The periods are described below: • Screening Period: This may involve one or more visits to the study site. • Double Blind Treatment Period: Treatment Period when participants will receive once weekly injections of anifrolumab or matching placebo. Participation will involve in-clinic study visits at Weeks 0 (Day 1), 1, 4, 8*, 16, 24, 36, 48 and 52. *The visit at Week 8 may be either by telephone or in person. • Open Label Treatment Period: At Week 52, all participants will be given anifrolumab 120 mg (subcutaneous) once weekly for 52 weeks (last dose at Week 103). Participation will involve in-clinic study visits at Weeks 52, 56, 64, 76. 88 and 104. • Safety Follow-up Period: All participants will return to the clinic for a 12-week post treatment visit. This will occur post Double Blind Treatment Period (Week 52 or Double Blind Period early discontinuation) or post Open Label Treatment Period (Week 104 or Open Label Period early discontinuation).

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Arms	Assigned Interventions
Experimental: Anifrolumab (subcutaneous weekly injection) Anifrolumab subcutaneous injection once weekly	Biological/Vaccine: Anifrolumab (blinded) Anifrolumab treatment delivered subcutaneously, once weekly for 52 weeks Other Name: Treatment arm (blinded) Biological/Vaccine: Anifrolumab (unblinded, open label) At Week 52, all patients will receive Anifrolumab subcutaneously once weekly for 52 weeks Other Name: Treatment arm (not blinded)
Placebo Comparator: matched placebo control (subcutaneous weekly injection) matched placebo control subcutaneous injection once weekly	Drug: Placebo (blinded) matched placebo delivered subcutaneously, once weekly for 52 weeks Other Name: Placebo arm (blinded)

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]