Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients

NCT ID: NCT01474122

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 265 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2014-02-28

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.

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.

Conditions

Digital Ulcers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Macitentan 3 mg

Oral macitentan 3 mg, once daily

Group Type: ACTIVE_COMPARATOR

Macitentan 3 mg

Intervention Type: DRUG

Macitentan 3-mg tablet once daily

Macitentan 10 mg

Oral macitentan 10 mg, once daily

Group Type: ACTIVE_COMPARATOR

Macitentan 10 mg

Intervention Type: DRUG

Macitentan 10-mg tablet once daily

Placebo

Oral placebo, once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablet matching macitentan tablet, once daily

Interventions

Macitentan 3 mg

Macitentan 3-mg tablet once daily

Intervention Type: DRUG

Macitentan 10 mg

Macitentan 10-mg tablet once daily

Intervention Type: DRUG

Placebo

Placebo tablet matching macitentan tablet, once daily

Intervention Type: DRUG

Other Intervention Names

ACT-064992; ACT-064992

Eligibility 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Khanna D, Denton CP, Merkel PA, Krieg T, Le Brun FO, Marr A, Papadakis K, Pope J, Matucci-Cerinic M, Furst DE; DUAL-1 Investigators; DUAL-2 Investigators. Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials. JAMA. 2016 May 10;315(18):1975-88. doi: 10.1001/jama.2016.5258.

Reference Type: RESULT

PMID: 27163986 (View on PubMed)

Other Identifiers

AC-055C302

Identifier Type: -

Identifier Source: org_study_id