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Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients (DUAL-2)

This study is currently recruiting participants.
Verified June 2013 by Actelion
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01474122
First received: October 31, 2011
Last updated: June 12, 2013
Last verified: June 2013
History of Changes
  Purpose

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 will continue on their original randomized treatment into Period 2, until the last randomized patient has completed Period 1.

Patients will be 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.

Condition Intervention Phase
Systemic Sclerosis
Ulcers
 Drug: macitentan 3mg
Drug: macitentan 10mg
Drug: placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Prospective, Randomized, Placebo-controlled, Double-blind, Mutlicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Patients With Schemic Digital Ulcers Associated With Systemic Sclerosis

Resource links provided by NLM:

MedlinePlus related topics: Scleroderma
U.S. FDA Resources

Further study details as provided by Actelion:

Primary Outcome Measures:
  • cumulative number of digital ulcers up to week 16 [ Time Frame: Period1: baseline (visit 2) to week 16. Period2: week 16 to end of study (which will occur when the last randomized patient, not prematurely withdrawn, has completed Period 1 and a 30 day safety follow-up period) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • hand functionality assessed through HDISS-DU PRO and HAQ-DI [ Time Frame: Period1: baseline (visit 2) to week 16. Period2: week 16 to end of study (which will occur when the last randomized patient, not prematurely withdrawn, has completed Period 1 and a 30 day safety follow-up period) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 285
Study Start Date: December 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: macitentan 3mg
macitentan tablet 3mg once daily
 Drug: macitentan 3mg
macitentan tablet 3mg once daily
Other Name: ACT-064992
Placebo Comparator: placebo
matching placebo once daily
 Drug: placebo
matching placebo once daily
Other Name: placebo
Active Comparator: macitentan 10mg
macitentan tablet 10mg once daily
 Drug: macitentan 10mg
macitentan tablet 10mg once daily
Other Name: ACT-064992

Detailed Description:

Recurrent digital ulcers (DU) are a manifestation of vascular disease in patients with systemic sclerosis (SSc), are an important source of morbidity and lead to impaired function in these patients. In this study, we are investigating whether treatment with the endothelin receptor antagonist, macitentan, decreases the development of new digital ulcers in patients with SSc. Macitentan is a highly potent, tissue-targeting dual endothelin receptor antagonist. Through complete blockade of endothelin action, macitentan is expected to protect tissue from the damaging effect of elevated endothelin. This therapy is not approved for the treatment of systemic sclerosis, but the use of an ERA is an attractive approach in combating the structural vascular damage observed in SSc leading to complications such as DUs.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ulcers(DU)

Exclusion Criteria :

  • DUs due to condition other than SSc
  • Symptomatic PAH
  • BMI < 18 kg/m2
  • AST and/or ALT > 1.5 x 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 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 ERAs within 3 months.
  • Systemic antibiotics to treat infected DU(s) within 4 weeks.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01474122

  Show 89 Study Locations
Sponsors and Collaborators
Actelion
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01474122     History of Changes
Other Study ID Numbers: AC-055C302
Study First Received: October 31, 2011
Last Updated: June 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
systemic sclerosis
digital ulcers

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Ulcer
 Connective Tissue Diseases
Skin Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on June 17, 2013