Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01474122




Registration number
NCT01474122
Ethics application status
Date submitted
31/10/2011
Date registered
18/11/2011
Date last updated
23/01/2017

Titles & IDs
Public title
Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients
Scientific title
Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Patients With Ischemic Digital Ulcers Associated With Systemic Sclerosis
Secondary ID [1] 0 0
AC-055C302
Universal Trial Number (UTN)
Trial acronym
DUAL-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Digital Ulcers 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Macitentan 3 mg
Treatment: Drugs - Macitentan 10 mg
Treatment: Drugs - Placebo

Active Comparator: Macitentan 3 mg - Oral macitentan 3 mg, once daily

Active Comparator: Macitentan 10 mg - Oral macitentan 10 mg, once daily

Placebo Comparator: Placebo - Oral placebo, once daily


Treatment: Drugs: Macitentan 3 mg
Macitentan 3-mg tablet once daily

Treatment: Drugs: Macitentan 10 mg
Macitentan 10-mg tablet once daily

Treatment: Drugs: Placebo
Placebo tablet matching macitentan tablet, once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence Rate of New Digital Ulcers (DUs) up to Week 16
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [1] 0 0
Percentage of Participants Without a New DU up to Week 16
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [2] 0 0
Percentage of Participants With at Least One DU Complication
Timepoint [2] 0 0
Up to 95 weeks
Secondary outcome [3] 0 0
Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16
Timepoint [3] 0 0
Baseline to Week 16
Secondary outcome [4] 0 0
Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16
Timepoint [4] 0 0
Baseline to Week 16
Secondary outcome [5] 0 0
Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16
Timepoint [5] 0 0
Baseline to Week 16

Eligibility
Key inclusion criteria
Inclusion Criteria :

- Patients = 18 years of age

- Women of childbearing potential must use two reliable methods of contraception

- Diagnosis of SSc according to the classification criteria of the American College of
Rheumatology (ACR)

- At least one visible, active ischemic DU at baseline

- History of at least one additional recent active ischemic digital ulcer
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria :

- DUs due to condition other than SSc

- Symptomatic pulmonary arterial hypertension (PAH)

- Body mass index (BMI) < 18 kg/m^2

- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 x upper
limit of normal (ULN)

- Hemoglobin < 75% of the lower limit of the normal range

- Systolic blood pressure < 95 mmHg or diastolic blood pressure < 50 mmHg

- Severe malabsorption; any severe organ failure (e.g., lung, kidney), or any
life-threatening condition

- Females who are pregnant or breastfeeding or plan to do so during the course of this
study

- Substance or alcohol abuse or dependence, or tobacco use at any level

- Treatment with phosphodiesterase-5 (PDE5) inhibitors

- Patients on statins, who have received treatment for less than 3 months prior to
Screening or whose treatment has not been stable during this period

- Patients on vasodilators, who have received treatment for less than 2 weeks prior to
Screening or whose treatment has not been stable during this period

- Treatment with prostanoids within 3 months

- Treatment with disease modifying agents if present for less than 3 months prior to
Screening or whose treatment has not been stable for at least 1 month prior to
Screening

- Treatment with oral corticosteroids (> 10 mg/day of prednisone or equivalent).

- Treatment with endothelin receptor antagonists (ERAs) within 3 months

- Systemic antibiotics to treat infected DU(s) within 4 weeks

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2014
Sample size
Target
Accrual to date
Final
265
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Connecticut
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District of Columbia
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Florida
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Illinois
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Massachusetts
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Missouri
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Ohio
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Pennsylvania
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Texas
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Utah
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Washington
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Wisconsin
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Argentina
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Buenos Aires
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Caba
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Cordoba
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Brussels
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Yvoir
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Beijing
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Shanghai
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Xi'an
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Bogota
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Muchen
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Muenchen
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Athens
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Amsterdam
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GA Nijmegen
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Moscow
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Soweto
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Barcelona
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Valencia
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Turkey
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Adana
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Izmir
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Ukraine
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Donetsk
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Kyiv
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Simferopol
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Vinnytsia
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Vinnytsya
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United Kingdom
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Bath
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Cambridge
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Liverpool
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London
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Manchester
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Scotland
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Torbay

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The DUAL-2 study is designed as a multicenter, double-blind two-period study with an initial
fixed 16-week Period 1, followed by a Period 2 of variable duration. All patients completing
Period 1 continue on their original randomized treatment into Period 2, until the last
randomized patient has completed Period 1.

Patients are randomized in a 1:1:1 ratio (macitentan 3mg: macitentan 10mg: placebo).

The primary objective is to demonstrate the effect of macitentan on the reduction of the
number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcers
(DU).

Other objectives include:

- the evaluation of the efficacy of macitentan on hand functionality and DU burden at Week
16 in SSc patients with ongoing DU disease.

- the evaluation of the safety and tolerability of macitentan in these patients.

- the evaluation of the efficacy of macitentan on time to first DU complication during the
entire treatment period.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01474122
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01474122