A study to evaluate whether macitentan is an effective and safe treatment for patients with heart failure with preserved ejection fraction and pulmonary vascular disease

• Register: EUCTR
• Last refreshed on: 3 May 2021
• Main ID: EUCTR2016-003653-15-AT
• Date of registration: 17/02/2017
• Prospective Registration: Yes
• Primary sponsor: ACTELION Pharmaceuticals Ltd
• Public title: A study to evaluate whether macitentan is an effective and safe treatment for patients with heart failure with preserved ejection fraction and pulmonary vascular disease
• Scientific title: A multi-center, double-blind, placebo-controlled Phase 2b study to evaluate the efficacy and safety of macitentan in subjects with heart failure with preserved ejection fraction and pulmonary vascular disease - SERENADE
• Date of first enrolment: 28/03/2017
• Target sample size: 147
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003653-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; 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: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, Bulgaria, Czech Republic, Denmark, France, Germany, Hungary, Israel, Poland, Romania, Russian Federation, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion criteria:
• Signs or symptoms of Heart Failure (HF) (NYHA FC II and III) requiring treatment with at least one oral diuretic (any type)
• Left Ventricular ejection fraction (LVEF) = 40% (by echocardiography at Screening)
• Structural heart disease consistent with heart failure with preserved ejection fraction (HFpEF) established by echocardiography at Screening
• Elevated NT-proBNP
• Pulmonary vascular disease or right ventricular dysfunction
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 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 129

Exclusion criteria:
• Any prior valid measurement of LVEF < 40%.
• Cardiovascular co-morbidities (e.g., significant unrepaired structural valvular heart disease; acute coronary syndrome, coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) within 3 months of Screening; uncontrolled heart rate from atrial fibrillation or atrial flutter, history of serious life-threatening or hemodynamically significant arrhythmia; history of or anticipated heart transplant or ventricular assist device implantation, etc)
• Systolic blood pressure (SBP) = 180 mmHg, or diastolic blood pressure (DBP) = 110 mmHg during Screening
• Hemoglobin < 100g/L (< 10 g/dl).
• Significant parenchymal lung disease (e .g., severe COPD, moderate or severe restrictive lung disease , diffuse interstitial fibrosis or alveolitis, pulmonary thromboembolism)
• Severe renal dysfunction with an estimated Glomerular Filtration Rate (eGFR ) < 30 m L/min per 1.73 m2
• Severe hepatic impairment, e .g., Child Pugh Class C.

Other protocol-defined inclusion/exclusion criteria may apply.

Strong CYP3A4 inhibitors such as ketoconazole, itraconazole,
voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir or a moderate dual CYP3A4/CYP2C9 inhibitor (eg,
fluconazoleor amiodarone) or co-administration of a combination of
moderate CYP3A4 (eg, ciprofloxacin, cyclosporine, diltiazem,
erythromycin, verapamil) and moderate CYP2C9 inhibitors (eg,
miconazole, piperine), in the 1-month period prior to baseline. This will
not necessarily apply to subjects who are already well-managed on such
an ongoing combination.


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Heart failure with preserved ejection fraction and pulmonary vascular disease
MedDRA version: 20.0 Level: LLT Classification code 10076397 Term: Noninfectious labyrinthitis System Organ Class: 100000004854

Intervention(s)

Trade Name: Opsumit
Product Name: macitentan
Product Code: ACT-064992
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)

Secondary Objective: The secondary objective of the study is to evaluate the effect of macitentan 10 mg as compared to placebo on:
– Quality of life
– Daily physical activity
– Worsening of heart failure

Main Objective: The primary objective of the study is to evaluate whether macitentan 10 mg reduces NT-pro-BNP versus placebo at Week 24 in subjects with HFpEF and pulmonary vascular disease

Primary end point(s): Primary efficacy endpoint(s)
• Percent of baseline NT-proBNP assessed at Week 24

Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints
• Change from baseline to Week 24 in the clinical summary score (as assessed by the Kansas City Cardiomyopathy Questionnaire [KCCQ])
• Change from baseline to Week 24 in accelerometer-assessed proportion of time spent in light to vigorous physical activity based on a threshold of > 100 activity counts per minute
• Time to worsening heart failure (WHF) event over 52 weeks as adjudicated by the Clinical Event Committee

Timepoint(s) of evaluation of this end point: Week 24, Week 52

Secondary ID(s)

2016-003653-15-DE

AC-055G202

Source(s) of Monetary Support

ACTELION Pharmaceuticals Ltd

Ethics review

Status: Approved
Approval date: 28/03/2017
Contact: