Trial Outcomes & Findings for Safety and Efficacy of Oral Treprostinil in the Treatment of Calcinosis in Patients With Systemic Sclerosis (NCT NCT02663895)

NCT ID: NCT02663895

Last Updated: 2021-06-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2021-06-10

Participant Flow

Participant milestones

Measure	Oral Treprostinil Treprostinil 0.125 mg three times daily (TID), increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Overall Study STARTED	12
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Oral Treprostinil Treprostinil 0.125 mg three times daily (TID), increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Overall Study Adverse Event	3
Overall Study Physician Decision	2
Overall Study Progressive Systemic Sclerosis (SSc)	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Participants with survey data are included in the analysis.

Baseline characteristics by cohort

Measure	Oral Treprostinil n=12 Participants 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 Oral treprostinil: Treprostinil 0.125 mg TID orally, which will be increased by 0.125 mg TID every 3 to 4 days as tolerated
Age, Continuous	55 years n=12 Participants
Sex: Female, Male Female	12 Participants n=12 Participants
Sex: Female, Male Male	0 Participants n=12 Participants
Race/Ethnicity, Customized Caucasian	9 Participants n=12 Participants
Race/Ethnicity, Customized Hispanic	2 Participants n=12 Participants
Race/Ethnicity, Customized African-American	1 Participants n=12 Participants
Region of Enrollment United States	12 Participants n=12 Participants
Disease Duration from First non-Raynaud symptom	12.3 years n=12 Participants
Ever Smoker	4 Participants n=12 Participants
Presence of diffuse cutaneous disease	6 Participants n=12 Participants
Calcinosis in Radiograph	171.1 score on a scale n=12 Participants
Scleroderma Health Assessment Questionnaire (SHAQ) HAQ-DI	1.4 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-Pain	1.2 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-GI	0.8 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-Breathing	0.5 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-Reynaud	0.9 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-DU	1.5 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-Disease Severity	1.4 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Cochin Hand Function Scale	21 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 Physical Functioning	32.5 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 Physical Role Functioning	0 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 Emotional Role Functioning	100 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 Energy Fatigue	30 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 Mental Health	76 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 Social Functioning	63 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 Pain	45 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 General Health	30 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Short Form (SF)-36 Health Change	25 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Raynaud Condition Score	3 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Patient Global Assessment	4 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Physician Global Assessment	5 score on a scale n=11 Participants • Participants with survey data are included in the analysis.
Mawdsley Questionnaire	4.83 score on a scale n=11 Participants • Participants with survey data are included in the analysis.

PRIMARY outcome

Timeframe: 12 months

Population: Of the 12 patients enrolled in this study, all received at least one dose of study treatment and were evaluated for safety.

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.

Outcome measures

Measure	Oral Treprostinil n=12 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Number of Participants With Treatment-related Adverse Events Following Treatment With Oral Treprostinil	11 Participants

PRIMARY outcome

Timeframe: Baseline, month 12

Population: Participants who completed the protocol are included in the analysis.

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.

Outcome measures

Measure	Oral Treprostinil n=5 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Median Rate of Change of Calcinosis in Radiograph Following Treatment With Oral Treprostinil as Assessed by a Novel Radiographic Scoring System	22.2 percent change Interval 5.3 to 85.5

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: Participants with survey data are included in the analysis.

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)

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Change in Scleroderma Health Assessment Questionnaire (SHAQ) HAQ-DI	0 score on a scale Interval -0.08 to 0.1
Change in Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-Pain	-0.03 score on a scale Interval -0.1 to 0.13
Change in Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-GI	0.03 score on a scale Interval 0.0 to 0.25
Change in Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-Breathing	0 score on a scale Interval -0.15 to 0.3
Change in Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-Raynaud	0 score on a scale Interval -0.1 to 0.2
Change in Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-DU	0 score on a scale Interval -0.15 to 0.1
Change in Scleroderma Health Assessment Questionnaire (SHAQ) SHAQ-VAS-Disease Severity	0 score on a scale Interval -0.05 to 0.1

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: Participants with survey data are included in the analysis.

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.

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Change in Cochin Hand Functional Scale	-0.17 score on a scale Interval -1.0 to 4.33

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: Participants with survey data are included in the analysis.

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.

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Change in Short Form (SF)-36 Physical Functioning	0 score on a scale Interval -33.3 to 8.3
Change in Short Form (SF)-36 Physical Role Functioning	0 score on a scale Interval 0.0 to 4.17
Change in Short Form (SF)-36 EMotional Role Functioning	0 score on a scale Interval -33.3 to 5.58
Change in Short Form (SF)-36 Energy and fatigue	0 score on a scale Interval -0.83 to 6.67
Change in Short Form (SF)-36 Mental Health	1 score on a scale Interval -1.33 to 6.67
Change in Short Form (SF)-36 Social Functioning	0 score on a scale Interval -8.33 to 6.17
Change in Short Form (SF)-36 Pain	0 score on a scale Interval -4.0 to 7.67
Change in Short Form (SF)-36 General Health	0.42 score on a scale Interval -1.67 to 3.33
Change in Short Form (SF)-36 Health Change	2.08 score on a scale Interval 0.0 to 8.33

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: Participants with survey data are included in the analysis.

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.

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Change in Mawdsley Calcinosis Questionnaire	2 score on a scale Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: Participants with survey data are included in the analysis.

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.

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Change in Raynaud Condition Score	0 score on a scale Interval -0.67 to 0.33

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: Participants with survey data are included in the analysis.

Patient global assessment of calcinosis severity at 1 year versus baseline. Score range: 0 to 10 (higher scores indicate more severe calcinosis).

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Change in Patient Global Assessment of Calcinosis Severity	0 score on a scale Interval -0.83 to 0.33

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: Participants with survey data are included in the analysis.

Physician global assessment of calcinosis severity at 1 year versus baseline. Score range: 0 to 10 (higher scores indicate more severe calcinosis).

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Change in Physician Global Assessment of Calcinosis Severity	-0.08 score on a scale Interval -0.33 to 0.33

SECONDARY outcome

Timeframe: Baseline visit (average approximately 3 hours for the scan)

Population: Participants with High Resolution peripheral Quantitative Computed Tomography device (HRpQCT) data were included in the analysis.

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.

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Baseline Cortical Area Measured by HR-pQCT in SSc Patients With Calcinosis.	104.8 mm^2 Interval 81.5 to 129.3

SECONDARY outcome

Timeframe: Baseline visit (average approximately 3 hours for the scan)

Population: Participants with High Resolution peripheral Quantitative Computed Tomography device (HRpQCT) data were included in the analysis.

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.

Outcome measures

Measure	Oral Treprostinil n=11 Participants Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Baseline Cortical Porosity Measured by HR-pQCT in SSc Patients With Calcinosis.	0.034 percentage of void space Interval 0.013 to 0.048

SECONDARY outcome

Timeframe: 12 months

Population: Data were not collected for this outcome measure.

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)

Outcome measures

Outcome data not reported

Adverse Events

Oral Treprostinil

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Oral Treprostinil n=12 participants at risk Treprostinil 0.125 mg TID, increased by 0.125 mg TID every 3 to 4 days as tolerated for 12-month period of time.
Nervous system disorders Headache	66.7% 8/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
Gastrointestinal disorders Abdominal Pain	50.0% 6/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
Gastrointestinal disorders Diarrhea	41.7% 5/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
Gastrointestinal disorders Nausea	25.0% 3/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
General disorders Flushing	16.7% 2/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
Musculoskeletal and connective tissue disorders Jaw Pain	16.7% 2/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
General disorders dizziness	16.7% 2/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
Cardiac disorders hypotension	8.3% 1/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
Ear and labyrinth disorders epistaxis	8.3% 1/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.
General disorders weight loss	8.3% 1/12 • Adverse event data were collected every 3 months up to 12 months and at 13 months from enrollment (3 months, 6 months, 9 month, 12 month and 13 months). Adverse event and serious adverse event were defined as per clinicaltrials.gov definitions.

Additional Information

Dr. Lorinda Chung

Stanford University

Phone: (650) 723-6961

Email: shauwei@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place