E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension (PAH) due to idiopathic pulmonary arterial hypertension (IPAH), familial PAH or PAH associated with connective tissue diseases (CTD) (e.g. systemic sclerosis, systemic lupus erythematosus) or to repaired congenital heart defects (RCHD). |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065151 |
E.1.2 | Term | Idiopathic pulmonary arterial hypertension |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065152 |
E.1.2 | Term | Familial pulmonary arterial hypertension |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065150 |
E.1.2 | Term | Associated with pulmonary arterial hypertension |
|
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 |
The primary objective of the study is to assess the efficacy of a number of doses of Aviptadil acutely and after 12 weeks of treatment. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to assess the safety and tolerability of a number of doses of Aviptadil. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for admission to the study, the following criteria must be met: 1. Male and female patients between 18 and 80 years of age with IPAH, familial PAH or PAH associated with CTD or RCHD. 2. Patients with NYHA/WHO functional class II or III. 3. Patients who have received stabilized therapy (i.e., therapy with [a] stable dose[s]) with an endothelin receptor antagonist approved for the treatment of PAH or a phosphodiesterase type 5 inhibitor approved for the treatment of PAH or a combination of both for at least 4 months prior to screening. 4. Symptomatic PAH diagnosed as either IPAH, familial PAH or PAH associated with CTD or RCHD clinically stable for at least 1 month prior to the inclusion. 5. An unencouraged 6-MWT of more than 200 meters but less than 550 meters at screening. 6. Prior cardiac catheterization consistent with PAH, specifically mean pulmonary arterial pressure (PAPm) > 25 mmHg (at rest), PCWP (or left ventricular end diastolic pressure) ≤ 15 mmHg and PVR > 3 mmHg/L/min. 7. Echocardiogram data acquired within 12 months prior to study drug administration that are consistent with PAH, specifically evidence of right ventricular hypertrophy or dilation, evidence of normal left ventricular function, and absence of mitral valve stenosis. 8. Chest radiograph or CT angiography consistent with the diagnosis of PAH generated within 12 months prior to study drug administration. 9. Able to understand and willing to sign the Informed Consent Form. 10. Results of pulmonary function tests (within the last 6 months) as follows: total lung capacity ≥ 60% predicted and forced expiratory volume in 1 second/forced vital capacity ≥ 50% predicted. |
|
E.4 | Principal exclusion criteria |
A patient may not enter the trial if any of the following criteria apply: 1. Patients with NYHA/WHO functional class I or IV. 2. Patients with PAH due to conditions other than IPAH, familial PAH or PAH associated with CTD or RCHD. 3. Patients who are on therapy with prostanoids, endothelin receptor antagonists not approved for the treatment of PAH or phosphodiesterase type 5 inhibitors not approved for the treatment of PAH. Note: Calcium channel blockers can be given according to the judgement of the Investigator and are not limited to a certain substance or dose. 4. Patients with Eisenmenger’s Syndrome (a condition where the patient has a septal defect of the heart or a persistent ductus arteriosus and where resulting pulmonary hypertension creates a reversal of the shunt). 5. Patients who have a new type of chronic therapy (e.g. a different category of vasodilator, diuretic) for PAH added within the last month, except anticoagulants. 6. Patients who have received therapy with an investigational drug within 3 months prior to the start of this study or who are scheduled to receive another investigational drug during the course of this study. 7. Patients who have discontinued regular medication or who have changed dose or class of any medication within the last week, except anticoagulants or insulin. 8. Patients with a concomitant disease that could interfere with their ability to perform the 6-MWT. 9. Patients with an acute concomitant disease that could potentially complicate the assessment of PAH disease severity or response to therapeutic intervention. 10. Patients with any illness other than PAH which might reduce life expectancy to less than 6 months. 11. Patients incapable or unwilling to sign the informed consent. 12. Patients pregnant and/or lactating. Females who plan to become pregnant during the study and females who are not using a highly effective method of birth control (failure rate less than 1% per year). 13. Patients with any pre-existing disease known to cause pulmonary hypertension unless listed in the inclusion criteria. The following pre-existing diseases are exclusionary: obstructive lung disease, parasitic disease affecting the pulmonary system, sickle cell anemia, mitral valve stenosis, portal hypertension and HIV infection. 14. Patients with a history of drug and/or alcohol abuse, as defined by the Investigator. 15. Patients with PAH associated with repaired congenital heart disease, who underwent the corrective surgery within 12 months prior to screening. 16. Patients taking prednisone at a dose higher than 20 mg/day. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the percentage change in PVR (peak PVR reduction compared to baseline PVR) after a single Aviptadil inhalation on Day 2, where baseline PVR is defined as the value measured when stability is reached prior to first investigational product inhalation at baseline (Base 2) and peak PVR is defined as the lowest value of PVR in post-baseline assessments (at 15, 30, 45, 60, 90, 120, 150 or 180 minutes). |
|
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 | Yes |
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 | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Open-label follow up after chronic treatment phase |
|
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | Information not present in EudraCT |
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 |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
Last visit of the last subject undergoing the trial. |
|
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 | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |