A Phase 3 Study of KHK4827 in Patients With Systemic Sclerosis

A Phase 3, Placebo-controlled, Double-blind Comparative Study of KHK4827 With an Open-label Extension Period in Subjects With Systemic Sclerosis Who Have Moderate to Severe Skin Thickening

To evaluate the efficacy and safety of KHK4827 in patients with systemic sclerosis who have moderate to severe skin thickening

Inclusion Criteria:

• Subject meets the criteria for diagnosis of the Diagnostic Criteria, Severity Classification, and Clinical Practice Guidelines for Systemic Sclerosis （Japanese Dermatological Association 2016） at the pre-examination
• Subject presented the first symptoms of sclerosis other than Raynaud's phenomenon within 60 months before enrollment
• Subject who has systemic sclerosis accompanied by moderate to severe skin thickening with an mRSS of 10 to <30 at the pre-examination and who has progressing skin thickening

Exclusion Criteria:

1. Any of the following significant concomitant diseases:

   • Type 1 diabetes
   • Poorly controlled type 2 diabetes (HbA1c > 8.5%)
   • Congestive heart failure (Class II to IV of the New York Heart Association Functional Classification)
   • Myocartial infarction, unstable angina, or stroke occurring within 12 months before the first dose of investigational product
   • Poorly controlled hypertension (systolic pressure > 150 mm Hg or diastolic pressure > 90 mg Hg at screening)
   • Severe chronic lung disease (%FVC < 60% and %DLco < 40%, calculated according to the Reference Values for Spirometry, Including Viral Capacity, in Japanese Adults Calcluated with the LMS Method and Compared with Previous Values [Japanese Respiratory Society])
   • Major chronic inflammatory diseases or connective tissue diseases other than scleroderma

2. Patient has a history or evidence of a psychiatric disorder, alcohol and/or substance abuse, or any other mental health disorder that, in the opinion of the investigators, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

3. Patient has a history or evidence of suicidal ideation (severity of 4 or 5) or any suicidal behavior based on an assessment with the Columbia-Suicide Severity Rating Scale (C-SSRS) at enrollment

4. Patient has severe depression based on a total score of ≥ 15 on the Patient Health Questionnaire-8 (PHQ-8) at enrollment