Trial record 1 of 1 for:    DUAL-2
Previous Study | Return to List | Next Study

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

This study has been terminated.
(company decision)
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01474122
First received: October 31, 2011
Last updated: January 19, 2015
Last verified: January 2015
  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, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Patients With Ischemic Digital Ulcers Associated With Systemic Sclerosis

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Incidence Rate of New Digital Ulcers (DUs) up to Week 16 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Without a New DU Up To Week 16 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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. Numbers of patients with no new DU at Week 16 are imputed using the last observation carried forward method.

  • Percentage of Participants With at Least One DU Complication [ Time Frame: Up to 95 weeks ] [ Designated as safety issue: No ]
    DU complications were defined as any one of the following, resulting from DU worsening: critical ischemic crisis necessitating hospitalization; gangrene, (auto)amputation; failure of conservative management; surgical and chemical sympathectomy, vascular reconstructions, or any unplanned surgery in the management of hand SSc manifestations; use of parenteral prostanoids; use of endothelin-receptor antagonists; class II, III, or IV narcotics or a > 50% increase in the existing dose compared with baseline; initiation of systemic antibiotics for the treatment of infection attributed to DUs.

  • Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    HAQ-DI assesses functional ability regarding fine movements of the upper extremities, locomotor activities in the lower extremities, and movements of the upper and lower limbs. Responses were extracted from the Scleroderma Health Assessment Questionnaire covering 8 domains of functional disability (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities). A mean score ranging from 0-3 was calculated for each domain, and a composite score by dividing the summed domain scores by the number of domains. The composite score was interpreted as 0 (no impairment in function) to 3 (maximal impairment of function). Hand functionality was assessed using a composite of 4 domains (dressing and grooming, grip, hygiene, and eating).

  • Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    HAQ-DI assesses functional ability regarding fine movements of the upper extremities, locomotor activities in the lower extremities, and movements of the upper and lower limbs. Responses were extracted from the Scleroderma Health Assessment Questionnaire covering 8 domains of functional disability (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities). A mean score ranging from 0-3 was calculated for each domain, and a composite score by dividing the summed domain scores by the number of domains. The composite score was interpreted as 0 (no impairment in function) to 3 (maximal impairment of function).

  • Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    Patients were asked to answer 24 questions on the use of the hand(s) affected by DUs over the past 7 days on a 6-point scale from 0 (yes without difficulty) to 5 (impossible). The HDISS-DU score is the arithmetic mean of the valid non-missing items. The scores are interpreted as 1 (better ability in completing activities) to 6 (worst ability in completing activities)


Enrollment: 265
Study Start Date: December 2011
Study Completion Date: February 2014
Primary Completion Date: February 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01474122

  Hide Study Locations
Locations
United States, California
Stanford Univ. School of Medicine - Palo Alto VA Health Care System
Palo Alto, California, United States, 94304
United States, Connecticut
University of Connecticut Health Center - Division of Rheumatic Diseases
Farmington, Connecticut, United States, 06030-1310
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
United States, Florida
Millennium Research
Ormond Beach, Florida, United States, 32174
Cleveland Clinic Florida
Weston, Florida, United States, 33331
Florida Medical Clinic-PA
Zephyrhills, Florida, United States, 33542
United States, Illinois
Northwestern University - Feinberg School of Medicine Department of Rheumatology
Chicago, Illinois, United States, 60611
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118-2394
United States, Missouri
Washington University School of Medicine
St Louis, Missouri, United States, 63110
United States, New York
North Shore Long Island Jewish Health System - Div. of Rheumatology & Allergy-Clinical Immunology
Lake Success, New York, United States, 11042
The Hospital for Special Surgery
New York, New York, United States, 10021
United States, Ohio
Ruppert Health Center
Toledo, Ohio, United States, 43614
United States, Pennsylvania
The University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas - Houston Medical School
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Arthritis Northwest PLLC
Spokane, Washington, United States, 99204
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Argentina
Centro de Educacion Medica e Investigaciones Clinicas - CEMIC
Buenos Aires, Argentina, 4102
Hospital Britanico de Buenos Aires
Buenos Aires, Argentina, C1280AEB
Hospital Italiano de Buenos Aires
Buenos Aires, Argentina
Sanatorio San Jose
Caba, Argentina, C1425DUH
Hospital Italiano de Cordoba
Cordoba, Argentina, X5004BAL
Hospital Privado Centro Medico de Cordoba S.A.
Cordoba, Argentina, x5016keh
Belgium
Clinique Universitaires Saint Luc
Brussels, Belgium, 1200
Cliniques universitaires UCL Mont-Godinne
Yvoir, Belgium, 5530
China
Peking Union Medical College Hospital
Beijing, China, 100032
Guangdong General Hospital
Guangzhou, China, 510080
Renji Hospital, Shanghai Jiaotong University
Shanghai, China, 200001
First Affiliated Hospital of the Forth Military University
Xi'an, China, 710032
Colombia
Hospital Pablo Tobon Uribe
Medellin, Antioquia, Colombia
Centro Integral de Reumatologia y Inmunologia CIREI SAS
Bogota, Colombia
Fundacion Instituto du Reumatologia Fernando Chalem
Bogota, Colombia
Germany
Kerckhoff-Klinik GmbH
Bad Nauheim, Germany, 61231
Universitätsklinikum der Technischen Universität Dresden
Dresden, Germany, 01307
Hautklinik Universitätsklinikum Erlangen
Erlangen, Germany, 91054
Department of Dermatology University Hospital Johannes Gutenberg
Mainz, Germany, 55131
Ludwig-Maximilian-Universität München Abteilung Dermatologie
Muchen, Germany, 80337
Klinik und Poliklinik für Dermatologie und Allergologie am Biderstein des Klinikums rechts der Isar der Technischen Universität München
Muenchen, Germany, 80802
Greece
General University Hospital LAIKO/A' Propaideftiki Pathology Clinic
Athens, Greece, 11527
EUROMEDICA - Kyanos Stavros
Thessaloniki, Greece, 54636
General University Hospital AHEPA
Thessaloniki, Greece, 54636
Ireland
Cork University Hospital
Cork, Ireland, C1
Beaumont Hospital
Dublin, Ireland, 2
St. Vincents University Hospital
Dublin, Ireland, 4
Mid-Western Regional Hospital
Limerick, Ireland
Israel
Sheba Medical Center
Tel-Hashomer, Israel, 52621
Asaf Harofe Medical Center
Zerifin, Israel, 70300
Mexico
Unidad de Investigacion en Enfermedades Cronico Degeneratives SC
Guadalajara, Jalisco, Mexico, 44620
Christus Muguerza del Parque Hospital
Chihuahua, Mexico, 31000
Clinica Diagnostico y Tratamiento de las Enfermedades Reumaticas
Distrito Federal, Mexico, 06700
Hospital Civil de Guadalajara - Fray Antonio Alacade Hospital No. 278
Guadalajara, Mexico, 44280
Hospital Aranda de la Parra Leon
Leon, Mexico, 37000
Hospital Angeles Lindavista
Madero, Mexico, 07760
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubrian
Mexico D.F., Mexico, 14000
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081
UMC St Radboud
GA Nijmegen, Netherlands, 6525
New Zealand
Middlemore Hospital
Auckland, New Zealand, 1640
Dunedin Hospital
Dunedin, New Zealand, 9054
Waikato Hospital
Hamilton, New Zealand, 3204
North Shore Hospital, STAR (Shore Trials and Research) Unit
North Shore, New Zealand, 0620
Wellington Hospital
Wellington South, New Zealand, 7902
Poland
Prywatna Praktyka Lekarska Prof. UM dr hab. med. Paweł Hrycaj
Poznań, Poland, 61-397
SPSK Nr 1 PUM Szczecin
Szczecin, Poland, 71-752
Reumatika - Centrum Reumatologii NZOZ
Warszawa, Poland, 02-653
Wojskowy Instytut Medyczny CSK MON
Warszawa, Poland, 04-141
SPSK Nr 1 Wrocław
Wrocław, Poland, 50-368
Portugal
Instituto Português de Reumatologia
Lisboa, Portugal, 1050-034
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00918
Russian Federation
State Institution, "Institute of Rheumatology of RAMS"
Moscow, Russian Federation, 115552
Municipal Treatment and Prevention Institution, "City Clinical Hospital #5"
Nizhniy Novgorod, Russian Federation, 603005
State Educational Institution of High Professional Education "Voronezh State Medical Academy named after N.N.Burdenko of Roszdrav"
Voronezh, Russian Federation, 394036
South Africa
Groote Schuur Hospital, University of Cape Town
Cape Town, South Africa, 7925
Louis Pasteur Medical Centre
Pretoria, South Africa, 0001
Chris Hani Baragwanath Hospital
Soweto, South Africa, 2013
Spain
HOSPITAL Universitario VALL D'HEBRON - Servicio Medicina Interna
Barcelona, Spain, 08035
Hospital Universitari i Politecnic La Fe
Valencia, Spain, 46026
Turkey
Çukurova Üniversitesi Tıp Fakültesi ROMATOLOJİ BİLİM DALI
Adana, Turkey, 01330
Dokuz Eylul Universitesi Tip Fakultesi Romatoloji Bilim Dali
Izmir, Turkey, 35340
Ukraine
Municipal Healthcare Institution "Donetsk Regional Clinical Hospital of Occupational Diseases"
Donetsk, Ukraine, 83059
National scientific centre "Institute of Cardiology named after M. Strazheska"
Kyiv, Ukraine, 03151
Crimean Republican Institution 'Clinical territorial medical union 'University Clinic
Simferopol, Ukraine, 95017
Vinnytsia Regional Clinical Hospital named after M. Pyrogov
Vinnytsia, Ukraine, 21018
Scientific and Research Institute of Handicapped Rehabilitation of Vinnitsa National Medical University named after M. Pirogova
Vinnytsya, Ukraine, 21029
United Kingdom
Royal National Hospital
Bath, United Kingdom, BA1 1RL
Addenbrooke's Hospital - University of Cambridge School of Clinical Medicine
Cambridge, United Kingdom, CB2 0QQ
University Hospital Aintree - Rheumatology Department
Liverpool, United Kingdom, L9 7AL
Royal Free & University College Medical School
London, United Kingdom, NW3 2PF
University of Manchester School of Translational Medicine Musculoskeletal Research Group
Manchester, United Kingdom, M13 9PT
Ninewells Hospital & Medical School
Scotland, United Kingdom, DD1 9SY
Torbay Hospital
Torbay, United Kingdom, TQ2 7AA
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
Results First Received: January 19, 2015
Last Updated: January 19, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
systemic sclerosis
digital ulcers

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

ClinicalTrials.gov processed this record on May 21, 2015