Safety and Efficacy of Oral Treprostinil in the Treatment of Calcinosis in Patients With Systemic Sclerosis
Condition: Systemic Sclerosis; Calcinosis
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Calcinosis; Sclerosis
Intervention: Oral treprostinil
Intervention description: Treprostinil 0.125 mg TID orally, which will be increased by 0.125 mg TID every 3 to 4 days as tolerated
Intervention MeSH terms: Treprostinil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a prospective open-label trial that will enroll 12 patients with systemic sclerosis
      (SSc) and at least one calcinotic lesion of the hands that is palpable on physical
      examination and also measureable on hand radiographs, at one single center. Each subject will
      receive treprostinil orally for 12 months, and follow-up evaluations will be performed every
      3 months. Our main objective is to determine whether oral treprostinil is safe, and effective
      in reducing calcinosis in patients with SSc. We hypothesize that calcinosis is a result of
      microvascular injury and ischemic damage, and that therefore treprostinil may be beneficial
      in the treatment of calcinosis in patients with SSc.
    

Eligibility criteria:

        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