Exploratory evaluation of pharmacokinetics and safety of KHK4827 in subjects with systemic sclerosis

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)
   • Myocardial 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 (%Forced Vital Capacity (FVC) < 60% and %Diffusing capacity of lung for carbon monoxide (DLco) < 40%, calculated according to the Reference Values for Spirometry, Including Viral Capacity, in Japanese Adults Calculated 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

There is a plan to make IPD and related data dictionaries available. The datasets generated and/or analyzed during the study sponsored by Kyowa Kirin will be available in the Vivli repository, https://vivli.org/ourmember/kyowa-kirin/ as long as conditions of data disclosure specified in the policy section of the Vivli website are satisfied.