trial of topical c-82 in systemic sclerosis - a phase i/ii biomarker and safety trial

Conditions: Systemic Scleroderma

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.

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.

Eligibility criteria:
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.

Keywords: systemic sclerosis scleroderma