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

JRCT ID: jRCT2051230127

Registered date:11/11/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Systemic Sclerosis, Scleroderma
• Date of first enrollment: 01/12/2023
• Target sample size: 32
• Countries of recruitment: Austria,Japan,Belgium,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Hungary,Japan,India,Japan,Israel,Japan,Italy,Japan,Mexico,Japan,Netherlands,Japan,Poland,Japan,Romania,Japan,South Africa,Japan,South Korea,Japan,Spain,Japan,Turkey,Japan,United Kingdom,Japan,United States of America,Japan
• Study type: Interventional
• Intervention(s): Approximately 306 eligible participants will be randomized on Day 1 in a 1:1 ratio to receive either anifrolumab 120 mg SC QW. Beginning with Week 52, all subjects will receive anifrolumab 120 mg SC QW for 52 weeks.

Outcome(s)

Primary Outcome

Number of participants responding to treatment based on the Revised Composite Response Index in Systemic Sclerosis (CRISS-25) [ Time Frame: at Week 52 ]
Number of participants meeting all the criteria:

Improvement in at least 2 components (5% or more increase for percent predicted Forced Vital Capacity (FVC) and/or 25% or more decrease for Modified Rodnan Skin Score (mRSS), Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Global Assessment (PtGA), Clinician Global Assessment (CGA)
Worsening in no more than one component ( 5% or more decrease percent predicted FVC and/or 25% or more increase for mRSS, HAQ-DI, PtGA, CGA)

No significant SSc-related event as defined by:
New scleroderma renal crisis New decline in percent predicted FVC 15% or more in established interstitial lung disease or new percent predicted FVC below 80% predicted New onset of left ventricular failure requiring treatment New onset of pulmonary arterial hypertension requiring treatment Gastrointestinal dysmotility requiring enteral or parenteral nutrition Digital ischemia with gangrene, amputation, or hospitalization requiring treatment

-Otherwise, a participant is a non-responder"

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 70age old
• Gender: Both

Include 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 more or PtGA score 3 points or more

6. mRSS > 10 with early disease or rapid progression as defined by the protocol

7. mRSS 15 or more with disease duration 18 months or more 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

Exclude 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

Related Information

• Primary Sponsor: Ageishi Yuji
• Secondary ID(s): NCT05925803