A Study of KHK4827 in Patients With Systemic Sclerosis

Study Overview
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Brief Summary
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Exploratory evaluation of pharmacokinetics and safety of KHK4827 in subjects with systemic sclerosis

Official Title
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A Phase 1, Open-label, Multiple-dose Study of KHK4827 in Subjects With Systemic Sclerosis

Conditions
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Systemic Sclerosis

Intervention / Treatment
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* Drug: KHK4827


Participation Criteria
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Eligibility Criteria
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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: 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 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 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 Patient has severe depression based on a total score of ≥ 15 on the Patient Health Questionnaire-8 (PHQ-8) at enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KHK4827<br> | Drug: KHK4827<br>* 210 mg every 2 weeks (Q2W), subcutaneous (SC) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum KHK4827 concentration |  | Pre-dose, Week 1, 2, 4, 8, 12, 16, 22, 24, 36, 48, 52 and every 24 weeks through study completion until 2023. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in modified Rodnan skin score (mRSS) from baseline | mRSS: scored 0(normal), 1(mild), 2(moderate), or 3(severe) per each site, assessed in 17 different body sites, total score=51 | Pre-dose, Week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every 8 weeks through study completion until 2023. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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systemic sclerosis, brodalumab, KHK4827