Open-Label Study of Oral Treprostinil in Digital Ulcers

Study Overview
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Brief Summary
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This open label extension trial will allow ongoing treatment of subjects who participated in the randomized controlled trials, and will provide long term information about the safety of treprostinil diethanolamine SR in subjects with SSc and digital ulcers.

Official Title
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Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine: An Open-label Multicenter Extension Study

Conditions
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Systemic Sclerosis

Intervention / Treatment
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* Drug: treprostinil diethanolamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible subjects who completed assessments for the final visit of the previous TDE-DU-201 controlled trial and who signed appropriate informed consent were eligible to enroll in this extension study. If a female of childbearing potential, the subject must have agreed to continue practicing an acceptable method of birth control (i.e., surgical sterilization, approved hormonal contraceptives, barrier methods [such as a condom or diaphragm] used with a spermicide, or an intrauterine device). Exclusion Criteria: Have had any change in clinical status that, in the opinion of the Investigator, would pose a safety risk for participation in this extension study; Have been found to be unable to complete study assessments in the previous controlled trial; Have prematurely discontinued study drug during the previous study due to clinical worsening or treatment related adverse events.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treprostinil<br>Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD). | Drug: treprostinil diethanolamine<br>* sustained release tablet; BID dosing; up to 16 mg BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net Ulcer Burden- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment | Net ulcer burden at any given assessment was defined as the number of new or active ulcers at that assessment, plus the number of indeterminate ulcers at that assessment that had previously been classified as either active or new at any earlier assessment during the study. The mean change in net ulcer burden from time of study entry was summarized for each scheduled visit assessment. | Baseline and Months 1, 3, 6, 9, 12, and 18 | 
| Total Ulcer Number- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment | The total ulcer number includes all ulcers designated as active, indeterminate, or new for a given visit. The mean change in the total number of ulcers present from time of study entry was summarized for each scheduled visit assessment. | Baseline and Months 1, 3, 6, 9, 12, and 18 | 
| Formation of New Ulcers | The number and percentage of subjects who developed new ulcers during the study were summarized. | 18 months (or last study visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Function and QOL Measure: Scleroderma Health Assessments Questionnaire (SHAQ)- Mean Change From Study Entry in SHAQ Component Scores at Each Scheduled Assessment | The SHAQ consists of 20 health assessment questionnaire questions with integer responses of 0 (without any difficulty) to 3 (unable to do), and five scleroderma-specific visual analog scale (VAS) domains (Overall Disease Activity, Raynaud's Phenomenon, Finger Ulcers, Breathing, and Intestinal Problems) with values ranging from 0.0 to 15.0 centimeters. The questions are divided into eight component domains: Dressing & Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each domain score is calculated by summing the domain responses and dividing by the number of questions in that domain. Each VAS domain score is calculated by dividing the value in centimeters by 5. SHAQ component and VAS domain score ranges from 0 (least limitation) to 3 (most limitation). The aggregate SHAQ score is calculated by dividing the sum of all domain scores by 13, with a score ranging from 0 (least limitation) to 3 (most limitation). | Baseline and Months 1, 3, 6, and 12 | 
| Patient Function and Quality of Life Measure: Cochin Hand Function Scale (CHFS)-Mean Change From Study Entry in CHFS Score at Each Scheduled Assessment | The CHFS score is derived from 18 validated questions that assess functional disability and handicap due to hand involvement in rheumatoid arthritis. Each answer is scored on a scale with possible integer responses of 0(without difficulty) to 5 (impossible). The CHFS score is simply the sum of all 18 questions, divided by the number of questions actually answered, multiplied by 18. At least 10 of the 18 questions must have been answered in order for CHFS to be calculated. Therefore, CHFS score values can range from 0 (least limitation) to 90 (most limitation), with improvements in function or reduction of limitation indicated a decreased score value. The mean change from study entry in CHFS scores at each scheduled assessment are summarized. | Baseline and Months 1, 3, 6, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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systemic sclerosis, scleroderma, digital ulcers, vasculopathy