A clinical research study with macitentan evaluating its effects on digital ulcers associated with systemic sclerosis (scleroderma)

• Register: EUCTR
• Last refreshed on: 27 October 2014
• Main ID: EUCTR2010-022710-77-DE
• Date of registration: 31/01/2011
• Prospective Registration: Yes
• Primary sponsor: Actelion Pharmaceuticals Ltd
• Public title: A clinical research study with macitentan evaluating its effects on digital ulcers associated with systemic sclerosis (scleroderma)
• Scientific 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 - DUAL-1: Digital Ulcers with mAcitentan in systemic scLerosis
• Date of first enrolment: 16/06/2011
• Target sample size: 285
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022710-77
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Australia, Belarus, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Finland, France, Germany, Hungary, India, Italy, Poland, Russian Federation, Ukraine, United States

Contacts

• Name: Global Medical Information
• Affiliation: Actelion Pharmaceuticals Ltd

• Name: Global Medical Information
• Affiliation: Actelion Pharmaceuticals Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Diagnosis of SSc according to the classification criteria of the American College of Rheumatology (ACR), or having ever met criteria for CREST syndrome (with sclerodactyly and 2 out of the 4 remaining criteria: calcinosis, Raynaud's phenomenon, esophageal dysfunction, telangiectasia).
- At least one visible, active ischemic DU at baseline, located at or distal to the proximal interphalangeal joints (PIP) or at the digital tip, and that developed or worsened within 8 weeks prior to screening.
- History of at least one additional active ischemic DU within 6 months, or at least two within 12 months prior to Screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 242
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 43

Exclusion criteria:
1. DUs due to condition other than SSc.
2. Symptomatic pulmonary arterial hypertension (PAH).
3. Body mass index (BMI: kg/m2) <18.
4. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal (ULN).
5. Hemoglobin < 75% of the lower limit of the normal range.
6. Systolic blood pressure < 95 mmHg or diastolic blood pressure < 50 mmHg.
7. Severe malabsorption, any severe organ failure (e.g., lung, kidney), or any life-threatening condition.
8. Comorbidities, other than SSc, that could seriously affect the assessment of hand function.
9. Females who are pregnant or breastfeeding or plan to do so during the course of this study.
10. Substance or alcohol abuse or dependence, or tobacco use.
11. Treatment with PDE5 inhibitors (e.g., sildenafil, tadalafil).
12. Patients on statins (e.g., atorvastatin, simvastatin), who have received treatment for less than 3 months prior to Screening (Visit 1) or whose treatment has not been stable during this period.
13. Patients on vasodilators, N-acetylcysteine, antiplatelet aggregation therapy and low molecular weight heparin who have received treatment for less than 2 weeks prior to Screening (Visit 1) or whose treatment has not been stable during this period.
14. Treatment with prostanoids.
15. Treatment with disease modifying agents such as methotrexate and cyclophosphamide if present for less than 3 months prior to Screening (Visit 1) or whose treatment has not been stable for at least 1 month prior to Screening (Visit 1).
16. Treatment with oral corticosteroids (> 10 mg/day of prednisone or equivalent).
17. Treatment with endothelin receptor antagonists (ERAs).
18. Systemic antibiotics (oral and i.v.) to treat infected DU(s).
19. Use of topical growth factors, hyperbaric oxygen.
20. Local injection of botulinum toxin in an affected finger within 4 weeks prior to Screening.
21. Surgical sympathectomy of the upper limbs or surgical wound debridement within 1 month prior to Screening.
22. Treatment with cytochrome P450 3A (CYP3A) inducers, such as rifabutin, rifampin, rifapentin, carbamazepine, phenobarbital, phenytoin, St. John’s wort, within 4 weeks prior to Screening.
23. Known hypersensitivity to drugs of the same class as the study drug, or any of the excipients.
24. Planned treatment, or treatment with another investigational drug within 4 weeks prior to Screening.
25. Any condition that prevents compliance with the protocol or adherence to therapy, including inability to speak, read, or understand the local language well enough to complete all study assessments.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ischemic digital ulcers associated with systemic sclerosis
MedDRA version: 14.0 Level: PT Classification code 10042953 Term: Systemic sclerosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: macitentan
Product Code: macitentan
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: macitentan
CAS Number: 441798-33-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: macitentan
Product Code: macitentan
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: macitentan
CAS Number: 441798-33-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Primary endpoint (assessed during Period 1) :
Cumulative number of new DUs up to Week 16.

Secondary Objective: _To evaluate the efficacy of macitentan on hand functionality and DU burden at Week 16 in systemic sclerosis (SSc) patients with ongoing DU disease.
_ To evaluate the safety and tolerability of macitentan in SSc patients with ongoing DU disease.
_To evaluate the efficacy of macitentan on time to first DU complication during the entire treatment period.

Main Objective: To demonstrate the effect of macitentan on the reduction of the cumulative number of new digital ulcers at Week 16 in patients with systemic sclerosis and ongoing digital ulcer (DU) disease.

Timepoint(s) of evaluation of this end point: End-of-Period 1 (Week 16)

Secondary Outcome(s)

Secondary end point(s): • Hand Functionality:
i. HDISS-DU
ii. HAQ-DI
• DU Burden:
i. Binary response of patients without a new DU
ii. Binary response of patients with more than 1, 2, 3, etc., new DU(s)
iii. Total number of DUs observed
iv. Time to onset of each new DU (1st, 2nd, 3rd, 4th, etc., DU)
• DU Complications: An event of DU complications is defined as the composite of the following:
i. Critical ischemic crisis necessitating patient hospitalization.
ii. Gangrene, (auto)amputation.
iii. Failure of conservative management: Surgical and chemical sympathectomy, vascular reconstructions, or any unplanned surgery in the management of hand manifestation(s).
iv. Use of parenteral prostanoids.
v. Use of endothelin receptor antagonists.
vi. Requiring class II, III or IV narcotics or increase in existing dose of > 50% as compared to baseline.
vii. Initiation of systemic antibiotics for the treatment of infection attributed to digital ulceration.

Timepoint(s) of evaluation of this end point: - Period 1: 4 visits (week 4, 8, 12 and 16)
- Period 2: variable number of visits every 3 month

Secondary ID(s)

AC-055C301

Source(s) of Monetary Support

Actelion Pharmaceuticals Ltd