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.

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.