Trial of Topical C-82 in Systemic Sclerosis - A Phase I/II Biomarker and Safety Trial

Phase 1

Completed

• Conditions: Systemic Scleroderma
• Interventions: Drug: C-82 Topical Gel, Placebo; Drug: C-82 Topical Gel, 1%

• Registration Number: NCT02349009
• Lead Sponsor: Prism Pharma Co., Ltd.

Brief Summary

1:1 active treatment: placebo, blinded trial, evaluating the effect of a 4-week treatment period with topical C-82 on skin expression of two gene biomarker surrogates (THBS1 and COMP) for the modified Rodnan skin score (MRSS). Study subjects will be randomized to apply the active study medication daily for 4 weeks to either the right or left forearm and placebo to the contralateral forearm.

Detailed Description

1:1 active treatment: placebo, blinded trial, evaluating the effect of a 4-week treatment period with topical C-82 on skin expression of two gene biomarker surrogates (THBS1 and COMP) for the modified Rodnan skin score (MRSS). Study subjects will be randomized to apply the study medication daily for 4 weeks to either the right or left forearm. All subjects will apply placebo (i.e., a topical gel without C-82) to the contralateral forearm. Both physician and subject will be blinded to treatment arm assignment. Skin biopsies will be taken from the mid-forearm of both arms at baseline and after four weeks of study drug to test for biomarker gene expression; instructions and supplies will be provided to each site. Safety assessments will extend to 4 weeks after the final dose of study drug/placebo.

Study Timeline

• Study First Submitted: 2015-01-18
• Study First Submitted QC: 2015-01-22
• Study First Posted: 2015-01-28
• Study Start: 2015-06
• Primary Completion: 2016-07
• Status Verified: 2016-09
• Study Completion: 2016-09
• Last Update Submitted: 2017-08-16
• Last Update Posted: 2017-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• meet the American College of Rheumatology criteria for systemic sclerosis with diffuse cutaneous involvement (clinical skin involvement proximal to forearms and or knees, not including the face).
• Disease duration of <36 months since the onset of the first SSc manifestation other than Raynaud's phenomenon, or patients with progressive disease based on new or worsening skin disease based on physician assessment.
• local skin score over the bilateral forearm of ≥ 2.
• a MRSS of ≥ 12.
• on stable dose of any immunosuppressive other than cyclophosphamide or high dose steroids (excluded treatments) for at least one month and through the course of study treatment.
• Subjects of child-producing potential must agree to use effective contraception while and for at least 3 months after the last treatment.

Exclusion Criteria

• Receiving treatment as part of an interventional clinical trial within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer).
• Ongoing use of high dose steroids (> 10mg/day prednisone or equivalent) or unstable steroid dose in the past 4 weeks.
• Use of topical creams or gels on the forearm area within the past month and through the course of study treatment.
• UV light therapy for 4 weeks before or during the study period.
• Treatment with cyclophosphamide within the past month and through the course of study treatment.
• Known active bacterial, viral fungal mycobacterial, or other infection
• history of malignancy within the past 2 years.
• Moderate to severe hepatic impairment, .
• Scleroderma renal crisis within 4 months or creatinine greater than 2.0.
• Pregnancy.
• Nursing mothers are to be excluded.
• Gastrointestinal involvement requiring total parenteral nutrition or hospitalization within the past 3 months for pseudo-obstruction
• Moderately severe pulmonary disease with FVC < 40%, or DLCO < 30% predicted or evidence of progressive lung disease as manifest by a decrease in FVC or 10% or more over the previous year.
• Moderately severe cardiac disease with clinically significant heart failure, or unstable angina.
• AST or ALT > 2.5 x Upper Limit of Normal.
• Total bilirubin > 1.5 x upper limit of normal (ULN). Patients with Gilbert's Disease may be included if their total bilirubin is ≤ 3.0 mg/dL.
• significant medical or psychosocial problems that warrant exclusion.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	C-82 Topical Gel, Placebo	C-82 Topical Gel, Placebo
Active	C-82 Topical Gel, 1%	C-82 Topical Gel, 1%

Primary Outcome Measures

Name	Time	Method
frequency and character of adverse events and abnormal clinical tests	28 days
change in gene biomarker expression of THBS1 and COMP in skin biopsies over time compared to placebo	28 days