Summary

Eligibility
for people ages 18-80 (full criteria)
Location
at UCSD
Dates
study started
estimated completion

Description

Summary

The purpose of the study is to evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with chronic thromboembolic pulmonary hypertension (CTEPH).

Official Title

A Prospective, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel Group, Adaptive Phase 3 Study With Open-label Extension to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension

Details

CTEPH is one of the leading causes of severe pulmonary hypertension (PH), classified within World Health Organization (WHO) group 4 PH. It is a rare, progressive pulmonary vascular disease that if left untreated, leads to progressively increasing pulmonary vascular resistance (PVR) and eventually right ventricle failure and death. Histopathologic findings including endothelial cell dysfunction and distal pulmonary arterial remodeling are shared between PAH and CTEPH, and PH-specific therapies (that is, riociguat) have shown efficacy in inoperable and persistent/recurrent CTEPH. The endothelin receptor antagonist macitentan offers a different mode of action and addresses an important unmet medical need for an alternative treatment option in this indication. This study will assess the effect of macitentan 75 mg on exercise capacity and is expected to confirm the role of macitentan as a first line, as well as add-on treatment for CTEPH. The study comprises of screening period (at least 14- and up to 60 days), a 52-week double-blind (DB) treatment period (which includes an 8-week up-titration phase), an open-label (OL) extension period (which starts at Week 52 and will end for all participants 104 weeks after the last participant has completed the DB treatment period) and 30-day safety follow-up period. Participants who discontinue DB study intervention will be followed until Week 52 in a post-treatment-observation period (PTOP). The total duration of the study is approximately 6 years.

Keywords

Chronic Thromboembolic Pulmonary Hypertension Hypertension, Pulmonary Hypertension Macitentan

Eligibility

You can join if…

Open to people ages 18-80

  • Chronic thromboembolic pulmonary hypertension (CTEPH) (World Health Organization [WHO]

Group 4) fulfilling one of the following criteria: a) inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), b) persistent/recurrent CTEPH after balloon pulmonary angioplasty (BPA), and deemed inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), c) persistent/recurrent CTEPH after rescue pulmonary endarterectomy (PEA)

  • 6-minute walk distance (6MWD) greater than or equal to (>=) 100 meter (m) and less than or equal to (<=) 450 meters (m), documented by an eligibility and a baseline 6-minute walk test (6MWT). The baseline 6MWD must not differ by more than 15 percent (%) from the eligibility test
  • World Health Organization functional class (WHO FC) >= II
  • Participants are to receive riociguat as per local standard of care, unless it is contraindicated or unavailable

You CAN'T join if...

  • Acute pulmonary embolism within 6 months prior to or during Screening
  • Planned (during the double-blind period of the study) balloon pulmonary angioplasty (BPA)
  • Significant obstructive and restrictive lung disease
  • Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements, in particular with 6MWT (for example, intermittent claudication).
  • Symptomatic coronary artery disease requiring an intervention within 3 months prior to or during Screening or anticipated during the DB period of the study
  • Decompensated cardiac failure if not under close supervision
  • Known and documented life-threatening cardiac arrhythmias
  • Acute myocardial infarction within 6 months prior to, or during Screening
  • Cerebrovascular events (including transient ischemic attack) within 3 months prior to, or during Screening
  • Known or suspicion of pulmonary veno-occlusive disease (PVOD)
  • Administration of ERAs, intravenous, or inhaled prostacyclins / prostacyclin analogs, or investigational treatment within 90 days prior to Randomization
  • Administration of riociguat within 90 days prior to Randomization (if its use as background medication becomes permissible based on pharmacokinetic Drug-drug interaction [DDI] data during the conduct of the study, this exclusion criterion will no longer apply)
  • Change in dose or initiation of Phosphodiesterase type-5 (PDE-5) inhibitors, oral prostacyclins / prostacyclin analogues, prostacyclin receptor agonists (or riociguat, if its use becomes permissible during the study) within 90 days prior to Randomization or anticipated during the 52-week double-blind [DB] period
  • Hypotension, that is, systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) <50 mmHg at Screening.
  • Severe renal dysfunction with an estimated Glomerular Filtration Rate <30 milliliters per minute per 1.73 meter square (mL/min/1.73 m2) using the Chronic Kidney Disease Epidemiology Collaboration formula at Screening

  • Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or C, based on records that confirm documented medical history
  • Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than or equal to (>=) 1.5*upper limit of normal (ULN) at Screening
  • Hemoglobin <100 g/L (<10 gram per deciliter [g/dL]) at Screening

Locations

  • University of California San Diego Medical Center not yet accepting patients
    La Jolla California 92093-0052 United States
  • USC Keck not yet accepting patients
    Los Angeles California 91105-2684 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Actelion
Links
To learn how to participate in this trial please click here.
ID
NCT04271475
Phase
Phase 3
Study Type
Interventional
Last Updated