Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients

NCT ID: NCT01474109

Last Updated: 2015-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 289 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-11-30

Brief Summary

The DUAL-1 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.

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

Systemic Sclerosis; Ulcers

Study Design

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

Study Groups

macitentan 3mg

macitentan 3mg tablet once daily

Group Type: ACTIVE_COMPARATOR

macitentan 3mg

Intervention Type: DRUG

macitentan 3mg tablet once daily

macitentan 10mg

macitentan 10mg tablet once daily

Group Type: ACTIVE_COMPARATOR

macitentan 10mg

Intervention Type: DRUG

macitentan 10mg tablet once daily

placebo

matching placebo once daily

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

matching placebo once daily

Interventions

macitentan 3mg

macitentan 3mg tablet once daily

Intervention Type: DRUG

macitentan 10mg

macitentan 10mg tablet once daily

Intervention Type: DRUG

placebo

matching placebo 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 digital ulcers (DU) at baseline
• History of at least one additional recent active ischemic DU

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 the normal range (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 type-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 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

Locations

University of Arizona Arthritis Center

Tucson, Arizona, United States

UCLA Medical School - Rheumatology Division Rehabilitation Center

Los Angeles, California, United States

Arthritis & Rheumatic Disease Specialties

Aventura, Florida, United States

Sarasota Arthritis Research Center

Sarasota, Florida, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

The Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

University of Michigan - Scleroderma Program

Ann Arbor, Michigan, United States

Michigan State University

Grand Rapids, Michigan, United States

University of Medicine & Dentistry of New Jersey, UMDNJ Scleroderma Program

New Brunswick, New Jersey, United States

The Center for Rheumatology

Albany, New York, United States

Shanahan Rheumatology and Immunotherapy, PLLC

Raleigh, North Carolina, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

University of Pittsburgh Department of Rheumatology

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Royal Adelaide Hospital

Adelaide, , Australia

Wesley Hospital, Thoracic Department

Auchenflower, , Australia

Royal Prince Alfred Hospital

Camperdown, , Australia

St Vincent's Hospital

Fitzroy, , Australia

Menzies Research Institute

Hobart, , Australia

Gomel Regional Clinical Hospital

Homyel, , Belarus

Healthcare Institution "Minsk City Hospital #1"

Minsk, , Belarus

Healthcare Institution "Minsk Clinical Hospital #9"

Minsk, , Belarus

Multiprofile Hospital for Active Treatment "Sveti Pantaleymon"

Pleven, , Bulgaria

MHAT "Kaspela" EOOD Plovdiv - Rheumatology Ward

Plovdiv, , Bulgaria

MHAT "Sv. Ivan Rilski" EAD Sofia - Clinic of Rheumatology

Sofia, , Bulgaria

Rheumatology Research Associates

Edmonton, Alberta, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

St. Joseph's Health Care

London, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

CHUS Hopital Fleurimont

Sherbrooke, Quebec, Canada

Prosalud

Santiago, , Chile

Private Office Marta Aliste

Santiago, , Chile

Hospital San Juan de Dios

Santiago, , Chile

Centro de Estudios Clinicos V

Viña del Mar, , Chile

Medicity S.A.S.

Bucaramanga, , Colombia

Servimed E.U.

Bucaramanga, , Colombia

Klinicki Bolnicki Centar Osijek

Osijek, , Croatia

University Hospital Centre Rijeka

Rijeka, , Croatia

Klinički bolnički centar Split

Split, , Croatia

Klinicka Bolnica "Svety Duh"

Zagreb, , Croatia

Klinička bolnica Dubrava

Zagreb, , Croatia

University Hospital Centre Zagreb

Zagreb, , Croatia

Lekarna FN Brno

Brno, , Czechia

Faculty Hospital Hradec Králové

Hradec Králové, , Czechia

Revmatologický ústav Praha

Prague, , Czechia

Bispebjerg Hospital København

Copenhagen, , Denmark

Odense Universitetshospital

Odense, , Denmark

Helsingin yliopistollinen keskussairaala (HYKS), Meilahden kolmiosairaala, Reumatologian klinikka

Helsinki, , Finland

Universitätsmedizin Berlin Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie

Berlin, , Germany

Klinik für Dermatologie und Allergologie der Ruhr-Universität Bochum

Bochum, , Germany

Klinik und Poliklinik für Dermatologie und Venerologie der Universität zu Köln

Cologne, , Germany

Medizinische Universitätsklinik Freiburg, Abt. Rheumatologie und klinische Forschung

Freiburg im Breisgau, , Germany

Asklepios Westklinikum Hamburg Abteilung für Gefäßmedizin, Angiologie und Diabetologie

Hamburg, , Germany

Rheumatologie, klinische Immunologie, Nephrologie Asklepios Rheumazentrum Hamburg Asklepios Klinik Altona

Hamburg, , Germany

Akademie für Gefäßkrankheiten eV.

Karlsbad, , Germany

Universitäts-Hautklinik Tübingen

Tübingen, , Germany

Budai Irgalmasrendi Kórház

Budapest, , Hungary

Debreceni Egyetem Orvos- és Egészségtudományi Centrum

Debrecen, , Hungary

Pécsi Tudományegyetem Klinikai Központ, Reumatológiai és Immunológiai Klinika

Pécs, , Hungary

Advance Rheumatology Clinic

Hyderabad, , India

Krishna Institute of Medical Sciences

Secunderabad, , India

Christian Medical College

Vellore, , India

Azienda Ospedaliera Careggi

Florence, , Italy

Azienda Ospedaliera Policlinico di Modena

Modena, , Italy

Complesso Integrato Columbus

Rome, , Italy

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

NZOZ Reumed

Lublin, , Poland

Centralny Szpital Kliniczny MSWiA

Warsaw, , Poland

Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu

Wroclaw, , Poland

State Healthcare Institution "Penza Regional Clinical Hospital named after N.N. Burdenko"

Penza, , Russia

Vladimir Regional State Institution of Healthcare, "Regional Clinical Hospital"

Vladimir, , Russia

State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"

Yekaterinburg, , Russia

Dinpropetrovsk Regional Clinical Hospital named after I. Mechnykova

Dnipropetrovsk, , Ukraine

Municipal Institution of Kyiv Regional Council, Kyiv Regional Clinical Hospital

Kyiv, , Ukraine

Lviv Regional Clinical Hospital

Lviv, , Ukraine

Internal disease chair of Ukrainian medical dentist academy based on therapy department of Poltava Poltava City Clinical Hospital #1

Poltava, , Ukraine

Countries

United States; Australia; Belarus; Bulgaria; Canada; Chile; Colombia; Croatia; Czechia; Denmark; Finland; Germany; Hungary; India; Italy; Poland; Russia; Ukraine

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: DERIVED

PMID: 27163986 (View on PubMed)

Other Identifiers

AC-055C301

Identifier Type: -

Identifier Source: org_study_id