Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients

NCT01474122 | Terminated Phase 3 Results DMC

• 1 other identifier: AC-055C302
• Study Type: interventional
• Target: 265
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Digital Ulcers

Keywords

digital ulcers; systemic sclerosis

Outcome Measures

Primary Outcomes (1)

• Incidence Rate of New Digital Ulcers (DUs) up to Week 16

  DUs were assessed at each visit starting with the screening visit. Only DUs from the proximal interphalangeal joint (PIP) distally (both on the dorsal and volar surface of the hand, including the digital tip) were recorded. The location of each DU was noted. At each subsequent visit the location of each new DU was noted. DUs that occurred and healed between visits and were reported by patients were not recorded as new DUs. The evaluation was performed by an experienced physician or a trained rater with expertise in the assessment of DUs in systemic sclerosis (SSc). For a given patient, DUs were assessed by the same rater at each visit, whenever possible. Any DU that developed over a previously healed ulcer was recorded as a new DU. Incidence rate is adjusted for 16 weeks of observation, hence is calculated as the number of new DUs/total number of observation days.

  Baseline to Week 16

Secondary Outcomes (5)

• Percentage of Participants Without a New DU up to Week 16

  Baseline to Week 16

• Percentage of Participants With at Least One DU Complication

  Up to 95 weeks

• Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16

  Baseline to Week 16

• Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16

  Baseline to Week 16

• Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16

  Baseline to Week 16

Study Arms (3)

Macitentan 3 mg

ACTIVE COMPARATOR

Oral macitentan 3 mg, once daily

Drug: Macitentan 3 mg

Macitentan 10 mg

ACTIVE COMPARATOR

Oral macitentan 10 mg, once daily

Drug: Macitentan 10 mg

Placebo

PLACEBO COMPARATOR

Oral placebo, once daily

Drug: Placebo

Interventions

Macitentan 3 mg DRUG

Macitentan 3-mg tablet once daily

Also known as: ACT-064992

Macitentan 3 mg

Macitentan 10 mg DRUG

Macitentan 10-mg tablet once daily

Also known as: ACT-064992

Macitentan 10 mg

Placebo DRUG

Placebo tablet matching macitentan tablet, once daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• 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.

  PMID: 27163986 RESULT

MeSH Terms

Conditions

digital ulcers; Scleroderma, Systemic

Interventions

macitentan

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

• Title: Angelina Marr
• Organization: Actelion Pharmaceuticals Ltd

angelina.marr@actelion.com

+41 61 565 63 69

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2011
• First Posted: November 18, 2011
• Study Start: December 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: February 4, 2025
• Results First Posted: January 28, 2015

Record last verified: 2025-01