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 long-term safety of LTP001 in participants with pulmonary arterial hypertension (PAH) |
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E.2.2 | Secondary objectives of the trial |
- To assess the effect of LTP001 on hemodynamic parameters derived from RHC - To assess the effect of LTP001 on the 6MWD - To assess the effect of LTP001 on measurements of right ventricular function - To assess the impact of LTP001 on Time to Clinical Worsening - To assess the impact of LTP001 on patient reported outcomes - To assess the impact of LTP001 on the N-terminal fragment of the prohormone B-type natriuretic peptide
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent must be obtained before any assessment is performed. • Participant is currently completing the Novartis-sponsored study CLTP001A12201 in PAH and completed key efficacy and safety procedures up to the end of treatment of the parent study, without meeting discontinuation criteria in the parent study. • Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures. • In the opinion of the Investigator the participant would benefit from LTP001 treatment.
Additional protocol-defined criteria may apply. |
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E.4 | Principal exclusion criteria |
• History of hypersensitivity to the study treatment. • Required or planned transplant or heart/lung surgery. • Acute or chronic impairment (other than dyspnea), which would limit the ability to comply with study requirements, including interference with physical activity or execution of study procedures such as 6MWT (e.g., angina pectoris, claudication, musculoskeletal disorder, need for walking aids). • Permanent discontinuation of Novartis drug in the parent study due to toxicity or disease progression, non-compliance to study procedures, withdrawal of consent or any other reason.
Additional protocol-defined criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
AEs, SAEs, vital signs, ECGs, safety laboratory measurements |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Baseline to End-Of-Study |
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E.5.2 | Secondary end point(s) |
• Change from baseline for each hemodynamic parameters derived from RHC • Change in 6MWD from baseline • Change from baseline in tricuspid annular plane systolic excursion (TAPSE) by echocardiography • Change from baseline in tricuspid annular systolic velocity (TASV) by echocardiography • Change from baseline of peak velocity of excursion (RV S') by echocardiography • Change from baseline in fractional area change (FAC) by echocardiography • Change from baseline in EmPHasis-10 and PAH-SYMPACT • Time to clinical worsening including time to death, hospital stay due to worsening of PAH, worsening of PAH resulting in need for lung transplantation • N-terminal fragment of the prohormone B-type natriuretic peptide |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At week 26 At week 26 and 52 At week 26 and 52 At week 26 and 52 At week 26 and 52 At week 26 and 52 At week 5, 13, 26, 39 and 52. From baseline to End-of-Study At weeks 5, 12, 26, 39 and 52. |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 10 |
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 |
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 | 11 |
E.8.9.1 | In the Member State concerned days | 4 |
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 | 6 |