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

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.