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

D3460C00002

The purpose of this study is to evaluate the efficacy and safety of treatment with subcutaneous anifrolumab versus placebo in adult participants with systemic sclerosis. The target population for this study includes patients who meet the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification for systemic sclerosis, either limited or diffuse cutaneous subsets, with a disease duration of less than 6 years from first non-Raynaud's phenomenon symptom.

2023-11-08

2026-10-09

2027-12-31

Recruiting

Early phase I

306

Key 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 Key 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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Subjects will be randomized in a 1:1 ratio to either anifrolumab or matching placebo for 52 weeks (double blind treatment period). At Week 52, all patients will be treated with 120 mg Anifrolumab for 52 weeks (open label treatment period).', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Double blind period- masking -everyone will be masked to the treatment allocation during the first 52 weeks Open label period - no masking- beginning at week 52, all participants will receive Anifrolumab for 52 weeks. During the open label period, there is no masking of study treatment, however, the treatment that participants received in the double blind period (first 52 weeks) will remain masked until the end of the study.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 306, 'type': 'ESTIMATED'}}

2024-01-09