Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients

NCT01474109 | Completed Phase 3 Results DMC

• 1 other identifier: AC-055C301
• Study Type: interventional
• Target: 289
• Locations: 18 countries
• Sites: 77

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.

Conditions

Systemic Sclerosis; Ulcers

Keywords

systemic sclerosis; digital ulcers

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 approximately 90 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 3mg

ACTIVE COMPARATOR

macitentan 3mg tablet once daily

Drug: macitentan 3mg

macitentan 10mg

ACTIVE COMPARATOR

macitentan 10mg tablet once daily

Drug: macitentan 10mg

placebo

PLACEBO COMPARATOR

matching placebo once daily

Drug: placebo

Interventions

macitentan 3mg DRUG

macitentan 3mg tablet once daily

Also known as: ACT-064992

macitentan 3mg

macitentan 10mg DRUG

macitentan 10mg tablet once daily

Also known as: ACT-064992

macitentan 10mg

placebo DRUG

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

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 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).

Sponsors & Collaborators

• Actelion: lead

Study Sites (77)

University of Arizona Arthritis Center

Tucson, Arizona, 85724, United States

Location

UCLA Medical School - Rheumatology Division Rehabilitation Center

Los Angeles, California, 90095, United States

Location

Arthritis & Rheumatic Disease Specialties

Aventura, Florida, 33180, United States

Location

Sarasota Arthritis Research Center

Sarasota, Florida, 34239, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

The Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224-6801, United States

Location

University of Michigan - Scleroderma Program

Ann Arbor, Michigan, 48109, United States

Location

Michigan State University

Grand Rapids, Michigan, 49546, United States

Location

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

New Brunswick, New Jersey, 08903-0010, United States

Location

The Center for Rheumatology

Albany, New York, 12206, United States

Location

Shanahan Rheumatology and Immunotherapy, PLLC

Raleigh, North Carolina, 27617-7884, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

University of Pittsburgh Department of Rheumatology

Pittsburgh, Pennsylvania, 15261, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425-8905, United States

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Wesley Hospital, Thoracic Department

Auchenflower, 4066, Australia

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

St Vincent's Hospital

Fitzroy, 3065, Australia

Location

Menzies Research Institute

Hobart, 7000, Australia

Location

Gomel Regional Clinical Hospital

Homyel, 246029, Belarus

Location

Healthcare Institution "Minsk City Hospital #1"

Minsk, 220013, Belarus

Location

Healthcare Institution "Minsk Clinical Hospital #9"

Minsk, 220116, Belarus

Location

Multiprofile Hospital for Active Treatment "Sveti Pantaleymon"

Pleven, 5800, Bulgaria

Location

MHAT "Kaspela" EOOD Plovdiv - Rheumatology Ward

Plovdiv, 4002, Bulgaria

Location

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

Sofia, 1612, Bulgaria

Location

Rheumatology Research Associates

Edmonton, Alberta, T5M 0H4, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

St. Joseph's Health Care

London, Ontario, N6A 4V2, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

CHUS Hopital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Prosalud

Santiago, 7510047, Chile

Location

Private Office Marta Aliste

Santiago, 7510186, Chile

Location

Hospital San Juan de Dios

Santiago, 8500000, Chile

Location

Centro de Estudios Clinicos V

Viña del Mar, 2570017, Chile

Location

Medicity S.A.S.

Bucaramanga, Colombia

Location

Servimed E.U.

Bucaramanga, Colombia

Location

Klinicki Bolnicki Centar Osijek

Osijek, 31000, Croatia

Location

University Hospital Centre Rijeka

Rijeka, 51000, Croatia

Location

Klinički bolnički centar Split

Split, 21000, Croatia

Location

Klinicka Bolnica "Svety Duh"

Zagreb, 10000, Croatia

Location

Klinička bolnica Dubrava

Zagreb, 10000, Croatia

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Lekarna FN Brno

Brno, 62500, Czechia

Location

Faculty Hospital Hradec Králové

Hradec Králové, 500 05, Czechia

Location

Revmatologický ústav Praha

Prague, 12000, Czechia

Location

Bispebjerg Hospital København

Copenhagen, 2400, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

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

Helsinki, 00290, Finland

Location

Universitätsmedizin Berlin Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie

Berlin, 10117, Germany

Location

Klinik für Dermatologie und Allergologie der Ruhr-Universität Bochum

Bochum, 44791, Germany

Location

Klinik und Poliklinik für Dermatologie und Venerologie der Universität zu Köln

Cologne, 50937, Germany

Location

Medizinische Universitätsklinik Freiburg, Abt. Rheumatologie und klinische Forschung

Freiburg im Breisgau, 79106, Germany

Location

Asklepios Westklinikum Hamburg Abteilung für Gefäßmedizin, Angiologie und Diabetologie

Hamburg, 22559, Germany

Location

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

Hamburg, 22763, Germany

Location

Akademie für Gefäßkrankheiten eV.

Karlsbad, 76307, Germany

Location

Universitäts-Hautklinik Tübingen

Tübingen, 72076, Germany

Location

Budai Irgalmasrendi Kórház

Budapest, 1023, Hungary

Location

Debreceni Egyetem Orvos- és Egészségtudományi Centrum

Debrecen, 4032, Hungary

Location

Pécsi Tudományegyetem Klinikai Központ, Reumatológiai és Immunológiai Klinika

Pécs, 7632, Hungary

Location

Advance Rheumatology Clinic

Hyderabad, 500082, India

Location

Krishna Institute of Medical Sciences

Secunderabad, 500 003, India

Location

Christian Medical College

Vellore, 632004, India

Location

Azienda Ospedaliera Careggi

Florence, 50139, Italy

Location

Azienda Ospedaliera Policlinico di Modena

Modena, 41100, Italy

Location

Complesso Integrato Columbus

Rome, 00168, Italy

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

NZOZ Reumed

Lublin, 20-607, Poland

Location

Centralny Szpital Kliniczny MSWiA

Warsaw, 02-507, Poland

Location

Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu

Wroclaw, 50-566, Poland

Location

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

Penza, 440026, Russia

Location

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

Vladimir, 600023, Russia

Location

State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"

Yekaterinburg, 620102, Russia

Location

Dinpropetrovsk Regional Clinical Hospital named after I. Mechnykova

Dnipropetrovsk, 49005, Ukraine

Location

Municipal Institution of Kyiv Regional Council, Kyiv Regional Clinical Hospital

Kyiv, 04107, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, 79010, Ukraine

Location

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

Poltava, 36039, Ukraine

Location

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 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Ulcer; digital ulcers

Interventions

macitentan

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: January 6, 2015
• Results First Posted: January 6, 2015

Record last verified: 2015-01

Locations

US (15); PL (4); BE (3); CA (5); CO (2); BU (3); UA (4); DK (2); AU (5); CL (4); HU (3); IT (3); RU (3); FI (1); DE (8); CR (6); IN (3); CZ (3)