Safety and Efficacy of Oral Treprostinil in the Treatment of Calcinosis in Patients With Systemic Sclerosis

Inclusion Criteria:

   - Signed written informed consent

   - Age > 18 years of age

   - Diagnosis of limited or diffuse cutaneous systemic sclerosis (SSc) according to the
   revised 2013 ACR/EULAR classification criteria for SSc

   - Radiological and physical examination evidence of at least one subcutaneous calcium
   deposition in the hands that is clinically apparent as part of routine clinical care.

   - If female of childbearing potential, the patient must have a negative pregnancy test
   at screening and baseline visits

   - Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) and NSAIDs are
   permitted if the patient is on a stable dose regimen for ≥ 2 weeks prior to screening
   and throughout the study

   - Calcium channel blockers, alpha-1-antagonists, ACE-inhibitors, angiotensin receptor
   blockers, and protein-pump inhibitors are permitted as long as the doses are stable
   for 4 weeks prior to screening and throughout the study

   - Women of childbearing potential must agree to use adequate contraception when sexually
   active with any combination of at least 2 effective methods of birth control (except
   for women who have a partner who is sterile, i.e. due to vasectomy)

Exclusion Criteria:

   - Rheumatic disease other than SSc

   - Patients with pulmonary arterial hypertension (PAH), NYHA Class III or IV, as
   determined by right heart catheterization or on PAH approved medications for PAH

   - Patients with moderate or severe hepatic impairment (Child Pugh Class C), or
   transaminase elevation (ALT or AST) > 3 x the upper limit of normal at screening visit

   - Patients with diverticulosis

   - Hemoglobin < 75% of the lower limit of the normal range

   - Systolic blood pressure < 95 mmHg or diastolic blood pressure < 50 mmHg

   - Patients who are hemodynamically unstable, or have acute renal, cardiac or pulmonary
   failure, or any life-threatening condition.

   - Concurrent malignancy except non-melanoma skin cancers

   - Patients receiving specific (sildenafil, tadalafil) or unspecific phosphodiesterase-5
   inhibitors (dipyridamole, theophylline), endothelin receptor antagonists, prostanoids,
   riociguat, or NO donors (nitrates) within 4 weeks of screening

   - Patients receiving bisphosphonates, warfarin, colchicine, minocycline, intravenous
   immunoglobulins, or biological agents including abatacept or rituximab within 4 weeks
   of screening

   - Patients receiving local treatments for calcinosis including surgical removal or
   intralesional steroid injections within 12 weeks of screening or throughout the study.

   - Patients who have participated in another clinical trial of an investigative agent
   within 30 days of screening (or 5 half-lives of the investigational drug, whichever is
   longer)

   - Pregnant or nursing women

   - Patients with a history of drug or alcohol abuse within 6 months of screening

   - Any medical condition that, in the opinion of the investigator, might interfere with
   the subject's participation in the study or poses an added risk for the subject

   - Inability to comply with study and follow-up procedures