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

NCT02663895 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 36140
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Systemic Sclerosis; Calcinosis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-related Adverse Events Following Treatment With Oral Treprostinil

  Number of participants with treatment-related adverse events following treatment with oral treprostinil at 12 months. We defined adverse event as any untoward medical experience occurring to a subject during a clinical trial whether or not it is related to the study drug.

  12 months

• Median Rate of Change of Calcinosis in Radiograph Following Treatment With Oral Treprostinil as Assessed by a Novel Radiographic Scoring System

  Median rate of change of calcinosis in radiograph following treatment with oral treprostinil as assessed by the Scleroderma Clinical Trial Consortium (SCTC) radiographic scoring system. Historical average SCTC scores in this patient population have ranged from 4.08 to 472.88, with higher scores indicating more severe symptoms. The SCTC radiographic score for calcinosis is a validated radiographic scoring system to assess the severity of calcinosis affecting the hands of patients with SSc that accounts for area coverage, density, and anatomic location, higher scores mean worse calcinosis. Physician rates density and percentage of area for 22 regions of each hand, each deferentially weighted in the overall score; individual region values are multiplied my their weight then summed to create an overall score.

  Baseline, month 12

Secondary Outcomes (10)

• Change in Scleroderma Health Assessment Questionnaire (SHAQ)

  Baseline, 12 months

• Change in Cochin Hand Functional Scale

  Baseline, 12 months

• Change in Short Form (SF)-36

  Baseline, 12 months

• Change in Mawdsley Calcinosis Questionnaire

  Baseline, 12 months

• Change in Raynaud Condition Score

  Baseline, 12 months

Study Arms (1)

Oral treprostinil

EXPERIMENTAL

Treprostinil 0.125 mg TID orally, which will be increased by 0.125 mg TID every 3 to 4 days as tolerated for 12 months

Drug: Oral treprostinil

Interventions

Oral treprostinil DRUG

Treprostinil 0.125 mg TID orally, which will be increased by 0.125 mg TID every 3 to 4 days as tolerated

Also known as: Orenitram

Oral treprostinil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• United Therapeutics: collaborator

Study Sites (1)

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

Related Publications (28)

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  PMID: 34718447 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Calcinosis

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Lorinda Chung
• Organization: Stanford University

shauwei@stanford.edu

(650) 723-6961

Study Officials

• Lorinda S Chung, MD, MS

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor of medicine (Immunology & Rheumatology)

Study Record Dates

• First Submitted: January 19, 2016
• First Posted: January 26, 2016
• Study Start: October 1, 2016
• Primary Completion: May 13, 2020
• Study Completion: May 13, 2020
• Last Updated: June 10, 2021
• Results First Posted: June 10, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)