GRIPHON: Prostacyclin (PGI2) Receptor agonist In Pulmonary arterial HypertensiON. A multicenter, double-blind, placebo-controlled Phase 3 study to demonstrate the efficacy and safety of ACT-293987 in patients with pulmonary arterial hypertension
The study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled, prospective Phase 3 study to compare the effects (defined as efficacy, safety, tolerability, PK/PD) of ACT-293987 (at the maximal tolerated dose of 200–1,600 µg b.i.d.) versus placebo over a period of up to 3.5 years. It is an event driven study which will be closed when 202 clinical worsening events will have been reached and adjudicated by the Critical Event Committee. The sample size is of 670 patients.
Patients will be up titrated from baseline to week 12 with weekly increments of 200 µg b.i.d. until reaching the individual maximum tolerated dose (MTD).
The first secondary endpoint, which is the change from baseline to week 26 in 6 Minutes walk distance, will be analyzed at Week 26 (visit 5, Month 6). After this time point, the visits will be performed every 6 months with a telephone call 3 months after each visit.
1. Signed informed consent prior to initiation of any study mandated procedure.
2. Male and female, patients aged from 18 years to 75 years inclusive with symptomatic PAH
3. Patients with PAH belonging to one of the following subgroups of the updated Dana Point Clinical
Classification Group 1:
• Idiopathic (IPAH) , or
• Heritable (HPAH)3, or
• Drug or toxin induced, or
• Associated (APAH) with one of the following:
– Connective tissue disease
– Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair
– HIV infection
4. Documented hemodynamic diagnosis of PAH by right heart catheterization – performed at any time prior to Screening showing:
• Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg
• Resting pulmonary vascular resistance (PVR) ≥ 400 dyn•s•cm5
• Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) <=15 mmHg
5. 6-minute walk distance (6MWD) between 50 and 450 m (inclusive) at Screening (within 2 weeks prior to the Baseline Visit and on a different day than this visit).
6. Patients who are able and willing to refrain from sunbathing, prolonged sun exposure, and artificial sunlight exposure like solarium use or UVA/UVB treatment, and to limit skin and eye exposure to sunlight using appropriate precautions (clothing, sunscreen, and sunglasses) from the first dose until 14 days after study drug discontinuation.