Phase 2 N=12 Treatment

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

Systemic Sclerosis · Calcinosis

Bottom Line

View on ClinicalTrials.gov: NCT02663895 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jun 2021

Primary outcome: Primary: Number of Participants With Treatment-related Adverse Events Following Treatment With Oral Treprostinil — 11 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Oral treprostinil (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Stanford University
Primary completion: May 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Treatment-related Adverse Events Following Treatment With Oral Treprostinil	11	—
PRIMARY Median Rate of Change of Calcinosis in Radiograph Following Treatment With Oral Treprostinil as Assessed by a Novel Radiographic Scoring System	22.2	—
SECONDARY Change in Scleroderma Health Assessment Questionnaire (SHAQ)	0; -0.03; 0.03; 0; 0; 0	—
SECONDARY Change in Cochin Hand Functional Scale	-0.17	—
SECONDARY Change in Short Form (SF)-36	0; 0; 0; 0; 1; 0	—
SECONDARY Change in Mawdsley Calcinosis Questionnaire	2	—
SECONDARY Change in Raynaud Condition Score	—	—
SECONDARY Change in Patient Global Assessment of Calcinosis Severity	—	—
SECONDARY Change in Physician Global Assessment of Calcinosis Severity	-0.08	—
SECONDARY Baseline Cortical Area Measured by HR-pQCT in SSc Patients With Calcinosis.	104.8	—
SECONDARY Baseline Cortical Porosity Measured by HR-pQCT in SSc Patients With Calcinosis.	0.034	—
SECONDARY Number of Patients With Changes in Vascular and SSc-Pulmonary Arterial Hypertension (PAH) Associated Biomarkers Following Treatment With Treprostinil at 1 Year Compared to Baseline	—	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02663895). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.