E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension |
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E.1.1.1 | Medical condition in easily understood language |
Disease in which blood vessels (arteries) in the lungs are damaged. This inhibits blood flow and pressure in the lung arteries rises and eventually heart failure develops |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of LTP001 in participants with pulmonary arterial hypertension |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of LTP001 on other efficacy measures, Patient reported outcomes and biomarkers - To assess the safety and tolerability of LTP001 in participants with PAH - To investigate the pharmacokinetics (PK) of LTP001
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- History of PAH belonging to one of the following subgroups of the Clinical Classification Group 1 (WHO): --> participants with idiopathic pulmonary arterial hypertension (IPAH) --> Hereditary pulmonary arterial hypertension --> Congenital heart disease (surgically repaired at least 12 months prior to screening) --> drug or toxin induced (for example, anorexigen or methamphetamine use) - Resting mean pulmonary arterial pressure > 25 mmHg; pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure < 15 mmHg as determined by right heart catheterization - Pulmonary Vascular Resistance > 6 Wood unites (480 dynes s/cm5), as determined by right heart catheterization - WHO Functional Class II-III - 6MWD must be between 150 and 550 m (inclusive). - Standard of care therapy which is stable at least 6 weeks prior to RHC and 6MWT assessment
Other protocol-defined criteria may apply. |
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E.4 | Principal exclusion criteria |
- Participants with pulmonary hypertension (PH) in the Clinical Classification Groups 2-5 (WHO), and any PAH Group 1 subgroups that were not covered by the inclusion criteria. - Participants with a history of left sided heart disease, chronic left sided heart failure, congenital or acquired valvular disease compromising left ventricular function and/or pulmonary venous hypertension or symptomatic coronary disease - Participants with obstructive lung disease defined as: FEV1/FVC < 60% and FEV1 < 60% of predicted value after bronchodilator administration as well as participants with moderate or severe restrictive lung disease: Total Lung Capacity < 70% of predicted value. - Acute or chronic impairment (other than dyspnea), which would limit the ability to comply with study requirements, including interference with physical activity and execution of study procedures such as 6MWT .
Other protocol-defined criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline PVR at week 25 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change from baseline in 6MWD at week 13 and week 25 - Right heart catheterization assessments including RV pressures, pulmonary artery pressures, wedge pressure, and cardiac output at week 25 - Change from baseline in tricuspid annular plane systolic excursion (TAPSE) by echocardiography at week 5, 13 and 25 - Change from baseline in tricuspid annular systolic velocity (TASV) by echocardiography at week 5, 13 and 25 - Change from baseline of peak velocity of excursion (RV S') by echocardiography at week 5, 13 and 25 - Change from baseline in fractional area change (FAC) by echocardiography at week 5, 13 and 25 - Change from baseline in EmPHasis-10 and PAH-SYMPACT at week 13 and 25 - AEs, SAEs, vital signs, ECGs, safety laboratory measurements - Time to Clinical Worsening - Cmax and Tmax (Week 1 and Week 25) - Change from baseline in N-terminal fragment of the prohormone B-type natriuetic peptide (NT-ProBNP) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At weeks 13 and 25 At week 25 At week 5, 13 and 25 At week 5, 13 and 25 At week 5, 13 and 25 At week 5, 13 and 25 At week 13 and 25 Baseline to Week 29 Baseline to Week 29 Week 1 and week 25 Baseline to Week 29
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Russian Federation |
United Kingdom |
United States |
Germany |
Netherlands |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |