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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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25 November 2019 |
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Main ID: |
EUCTR2007-002440-14-GB |
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Date of registration:
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26/11/2007 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A multicenter, double-blind, randomized, placebo-controlled, parallel group, event-driven, Phase III study to assess the effects of ACT-064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertension - SERAPHIN
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Scientific title:
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A multicenter, double-blind, randomized, placebo-controlled, parallel group, event-driven, Phase III study to assess the effects of ACT-064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertension - SERAPHIN |
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Date of first enrolment:
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15/05/2008 |
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Target sample size:
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700 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002440-14 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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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
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Austria
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Belgium
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Bulgaria
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Denmark
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Finland
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France
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Germany
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Italy
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Netherlands
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Portugal
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Slovakia
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Sweden
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
1.Signed informed consent prior to initiation of any study mandated procedure.
2.Patients with symptomatic pulmonary arterial hypertension (PAH) in modified WHO functional class II to IV.
3.Patients with the following types of PAH belonging to groups 1.1 to 1.3 of the Venice classification:
a.Idiopathic (IPAH);
b.Familial (FPAH); or
c.Related to:
i.Collagen vascular disease;
ii.Simple, congenital systemic-to-pulmonary shunts at least 1 year post surgical repair;
iii.HIV infection; or
iv.Drugs and toxins.
4.PAH diagnosis confirmed by hemodynamic evaluation performed prior to randomization and showing all of the following:
a.Mean pulmonary artery pressure (mPAP) > 25 mmHg at rest;
b.Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) <= 15 mmHg; and
c.Pulmonary vascular resistance (PVR) at rest >= 320 dyn*sec/cm5.
?For patients who participate in the pharmacokinetic/ pharmacodynamic substudy, hemodynamic evaluation must have been performed within 3 months prior to randomization.
?For all other patients, hemodynamic evaluation must have been performed within 1 year prior to randomization.
5.6-minute walk distance (6MWD) >= 50 m at screening and randomization
The 6MWT performed at screening and randomization must satisfy the following
requirements:
• 6MWT distance must be > 50 m or patient cannot be included in the study.
• 6MWT #2 (at Randomization) distance should be within 10% of 6MWT #1
distance (at Screening) or a third test is required (6MWT #3).
• 6MWT #3 (at Randomization) distance should be within 10% of 6MWT #2
distance or the patient cannot be included in the study.
6.Men or women >= 12 years of age (women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception, men with a female partner of child-bearing potential should use a condom).
Are the trial subjects under 18? yes
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
1.PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher’s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy.
2.PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected.
3.PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
4.Persistent pulmonary hypertension of the newborn.
5.Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification.
6.Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 65% of predicted value after bronchodilator administration.
7.Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value.
8.Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
9. Estimated Creatinine clearance <30mL/min
10.Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal.
11.Hemoglobin < 75% of the lower limit of the normal range.
12.Systolic blood pressure < 100 mmHg.
13.Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
14.Pregnant or breast-feeding.
15.Known concomitant life-threatening disease with a life expectancy < 12 months.
16.Body weight < 40 kg.
17.Any condition that prevents compliance with the protocol or adherence to therapy.
18.Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise.
19.Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.
20.Systemic treatment within 4 weeks prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mTOR inhibitors).
21. Treatment with CYP3A inducers within 4 weeks prior to randomization.
22.Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
23.Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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To assess the effects of ACT-064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertension
MedDRA version: 9.1
Level: LLT
Classification code 10064911
Term: Pulmonary arterial hypertension
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Intervention(s)
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Product Name: ACT-064992
Product Code: ACT-064992
Pharmaceutical Form: Tablet
CAS Number: 441798-33-0
Current Sponsor code: ACT-064992
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: -3
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Product Name: ACT-064992
Product Code: ACT-064992
Pharmaceutical Form: Tablet
CAS Number: 441798-33-0
Current Sponsor code: ACT-064992
Other descriptive name: ACT-064992
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: -10
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
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Primary Outcome(s)
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Main Objective: •To demonstrate that either dose of ACT-064992 prolongs the time to the first morbidity or mortality event in patients with symptomatic pulmonary arterial hypertension.
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Primary end point(s): Primary endpoint
Time from start of treatment to first morbidity or mortality event, defined as follows:
1.Death, or
2.Atrial septostomy, or
3.Lung transplantation, or
4.Initiation of intravenous or subcutaneous prostanoids (e.g., epoprostenol, treprostinil), or
5.Other worsening of pulmonary arterial hypertension.
Other worsening of pulmonary arterial hypertension is defined by the combination of all of the three following components:
•A decrease in 6MWD of at least 15% from baseline that should be confirmed by two 6-minute walk tests, performed on different days, within 2 weeks
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•Worsening of PAH symptoms (1)
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•Need for new treatment(s) for PAH (2)
(1) Worsening of PAH symptoms must include at least one of the following:
?WHO functional class increased, or no change in patients in WHO class IV at baseline
?Appearance or worsening of signs/symptoms of right heart failure that did not respond to oral diuretic therapy
(2) New treatments for PAH are:
?oral or inhaled prostanoids (e.g., iloprost)
?oral phosphodiesterase inhibitors (e.g., sildenafil)
?endothelin receptor antagonists (e.g., bosentan, ambrisentan, sitaxsentan) only after discontinuation of the study drug
?intravenous diuretics
An independent Clinical Event Committee (CEC) will review and confirm all reported mortality and morbidity events in a blinded fashion.
The observation period for the primary endpoint will start with first study drug intake, and end with EOT plus 1 week.
Patients who prematurely discontinue study treatment without a morbidity or mortality event will be censored at the time of study treatment discontinuation plus 1 week (censoring rate is expected to be 5%/year, and to be similar in all treatment groups).
The hazard of a morbidity/mortality event in one group relative to the other is not expected to change with time, and the event rate in the placebo group is expected to be 24.8% per year. The treatment effect to be detected is a reduction of 41.8% of the event rate to 14.4%.
Secondary endpoints
These will be analyzed in the following sequence:
1.Change from baseline to Month 6 in 6MWD
2.Change from baseline to Month 6 in modified WHO functional class
3.Time to death due to PAH or hospitalization for PAH up to EOT
4.Time to death of all causes up to EOT
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Secondary Objective: •To demonstrate that either dose of ACT-064992 improves exercise capacity and WHO functional class, and prolongs the time to death or hospitalization for PAH in patients with symptomatic pulmonary arterial hypertension.
•To evaluate the safety and tolerability of ACT-064992 in patients with symptomatic pulmonary arterial hypertension.
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Secondary ID(s)
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AC-055-302
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date:
Contact:
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