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Trial record 6 of 7 for:    treprostinil | scleroderma

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

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ClinicalTrials.gov Identifier: NCT02663895
Recruitment Status : Completed
First Posted : January 26, 2016
Results First Posted : June 10, 2021
Last Update Posted : June 10, 2021
Sponsor:
Collaborator:
United Therapeutics
Information provided by (Responsible Party):
Lorinda S Chung, Stanford University

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.

Condition or disease Intervention/treatment Phase
Systemic Sclerosis Calcinosis Drug: Oral treprostinil Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study to Evaluate the Safety and Efficacy of Oral Treprostinil in the Treatment of Calcinosis in Patients With Systemic Sclerosis
Study Start Date : October 2016
Actual Primary Completion Date : May 13, 2020
Actual Study Completion Date : May 13, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scleroderma

Arm Intervention/treatment
Experimental: Oral treprostinil
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
Treprostinil 0.125 mg TID orally, which will be increased by 0.125 mg TID every 3 to 4 days as tolerated
Other Name: Orenitram




Primary Outcome Measures :
  1. Number of Participants With Treatment-related Adverse Events Following Treatment With Oral Treprostinil [ Time Frame: 12 months ]
    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.

  2. Median Rate of Change of Calcinosis in Radiograph Following Treatment With Oral Treprostinil as Assessed by a Novel Radiographic Scoring System [ Time Frame: Baseline, month 12 ]

    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.



Secondary Outcome Measures :
  1. Change in Scleroderma Health Assessment Questionnaire (SHAQ) [ Time Frame: Baseline, 12 months ]

    The Scleroderma Health Assessment Questionnaire (SHAQ) has two parts.

    The first part is a disability index (DI) that consists of the mean of 8 scores from 8 sections (dressing, arising, eating, walking, hygiene, reach, grip, and activities) ranging from 0 (without any difficulty) to 3 (unable to do), with scores summed and divided by 8. The result is the Health Assessment Questionnaire (HAQ)-DI score, which ranges between 0 and 3.

    The second part consists of 6 visual analogue scales (VAS) each ranging from 0 (better outcome) to 10 (worse outcome).

    • Pain (SHAQ-VAS-Pain)
    • Intestinal (SHAQ-VAS-GI)
    • Breathing (SHAQ-VAS-Breathing)
    • Raynaud (SHAQ-VAS-Raynaud)
    • Digital ulcers (SHAQ-VAS-DU)
    • Disease Severity (SHAQ-VAS-Disease Severity)

  2. Change in Cochin Hand Functional Scale [ Time Frame: Baseline, 12 months ]
    Cochin Hand Functional Scale is a 18-question scale, each question ranges from 0 to 5, with a total score range of 0-90. Higher scores indicates higher disability.

  3. Change in Short Form (SF)-36 [ Time Frame: Baseline, 12 months ]
    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The higher the score the less disability.

  4. Change in Mawdsley Calcinosis Questionnaire [ Time Frame: Baseline, 12 months ]
    Mawdsley Calcinosis Questionnaire is an 18-question survey with an overall score of 0-10; each individual question ranges from 0-10, scores are totaled and averaged to and divided by 18 to create the overall score. Higher scores indicate higher disability from calcinosis.

  5. Change in Raynaud Condition Score [ Time Frame: Baseline, 12 months ]
    The Raynaud Condition Score is a single question questionnaire, ranges from 0-10, where 10 indicates more active Raynaud phenomenon. Raynaud is an exaggerated vascular response to cold exposure or emotion with at least a 2-phase color change in finger(s) and often toe(s) consisting of pallor, cyanosis, and/or reactive hyperemia: usually one phase is pallor.

  6. Change in Patient Global Assessment of Calcinosis Severity [ Time Frame: Baseline, 12 months ]
    Patient global assessment of calcinosis severity at 1 year versus baseline. Score range: 0 to 10 (higher scores indicate more severe calcinosis).

  7. Change in Physician Global Assessment of Calcinosis Severity [ Time Frame: Baseline, 12 months ]
    Physician global assessment of calcinosis severity at 1 year versus baseline. Score range: 0 to 10 (higher scores indicate more severe calcinosis).

  8. Baseline Cortical Area Measured by HR-pQCT in SSc Patients With Calcinosis. [ Time Frame: Baseline visit (average approximately 3 hours for the scan) ]
    Bone cortical area is a bone microarchitecture measurement assessed by High Resolution peripheral Quantitative Computed Tomography (HRpQCT) at the distal tibia. Lower levels of cortical area are associated with more bone fragility.

  9. Baseline Cortical Porosity Measured by HR-pQCT in SSc Patients With Calcinosis. [ Time Frame: Baseline visit (average approximately 3 hours for the scan) ]
    Bone cortical porosity is a bone microarchitecture measurement assessed by High Resolution peripheral Quantitative Computed Tomography (HRpQCT) at the distal tibia. Higher levels of cortical porosity are associated with more bone fragility.

  10. 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 [ Time Frame: 12 months ]
    SSc-PAH associated biomarkers following treatment with treprostinil at 1 year compared to baseline. Ang-1 Ang-2 MMP-2, MMP-9 NT-proBNP, PIGF VEGFR1, sRAGE GLUT-1 Ficolin-1 MBL H62 plex (includes VEGF, PDGFBB, bFGF,IL-13, HGF, IL-6, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13,[TNF]-α,[IFN]-γ)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02663895


Locations
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United States, California
Stanford University School of Medicine
Palo Alto, California, United States, 94304
Sponsors and Collaborators
Stanford University
United Therapeutics
Investigators
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Principal Investigator: Lorinda S Chung, MD, MS Stanford University
  Study Documents (Full-Text)

Documents provided by Lorinda S Chung, Stanford University:
Publications:

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Responsible Party: Lorinda S Chung, Associate professor of medicine (Immunology & Rheumatology), Stanford University
ClinicalTrials.gov Identifier: NCT02663895    
Other Study ID Numbers: 36140
First Posted: January 26, 2016    Key Record Dates
Results First Posted: June 10, 2021
Last Update Posted: June 10, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Treprostinil
Calcinosis
Sclerosis
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Antihypertensive Agents