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

• Status: Completed
• Trial end date: 2020-05-13
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stanford University
• Collaborator: United Therapeutics
• Treatments: Treprostinil

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