AC-065A303 (GRIPHON OL), Long-term single-arm open-label study, to assess the safety and tolerability of ACT-293987 in patients with pulmonary arterial hypertension

Study ID
STU 062010-012

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern University Hospital—St. Paul

Contact
Jacqueline Quivers
214-645-6489
jacqueline.quivers@utsouthwestern.edu

Principal Investigator
Kelly Chin

Summary

Patients (males or females aged 18 years or older) from the study aC 065a302/GRiPHon will be enrolled in this oL study .The study will be conducted in approximately 190 centers in 44 countries.

The subjects will enter this open label study by two means: 1). Completed the double-blind study aC 065a302/GRiPHon or if they experience clinical worsening of PaH during the study aC 065a302/GRiPHon.

Clinical worsening is defined:
* Hospitalization for worsening of PaH based on predefined criteria
or
* Worsening of PaH resulting in need for lung transplantation or balloon atrial septostomy
or
* initiation of parenteral* prostanoid therapy or chronic oxygen therapy due to worsening of PaH
or
* Disease progression (patients in modified nYHa/WHo functional class ii-iii at baseline) confirmed by :
x decrease in 6MWD from Baseline ([GreaterThanorequalTo] 15%, confirmed by 2 tests on different days within 2 weeks) and
x worsening of nYHa/WHo functional class
or
* Disease progression (patients in modified nYHa/WHo functional class iii-iV at baseline) confirmed by :
x decrease in 6MWD from Baseline ([GreaterThanorequalTo] 15%, confirmed by 2 tests on different days within 2 weeks) and
x need for additional PaH specific therapy

Subjects with clinical worsening that participated in the blinded trial who are already on drug and participate in this open-label trial will have a lower dose than what was previous provided in the blinded trial. Currently, it seems that subjects with clinical worsening would be at greater risk due to lowering their dose than a subject that was on placebo.

each patient will be on aCT-293987 at his/her individual highest tolerated dose. Depending on the highest tolerated dose of the patient, a single dose will consist of 1 to 8 tablets (200 [MiCRo-SYMBoL]g to 1600 [MiCRo-SYMBoL]g) b.i.d. Patients coming from study aC 065a302/GRiPHon already taking aCT-293987, will continue on the same dose. Patients who were on placebo and patients who experienced a clinical worsening of PaH (adjudicated by the CeC) during study aC 065a302/GRiPHon, will start aCT 293987 at a low dose (200 [MiCRo-SYMBoL]g b.i.d) and will be up-titrated until their highest tolerated dose is reached. Patients with a clinical worsening of PaH (adjudicated by the CeC) will be transferred from the double-blind study aC 065a302/GRiPHon to the oL study without knowledge of their previous treatment arm (aCT-293987 or placebo) to preserve the integrity of the double-blind study.

The study protocol allows the use of PaH specific medications such as endothelin Receptor antagonists (eRas) and/or PDe-5 (Phosphodiesterase-5) inhibitors as background therapy. only prostacyclin (epoprotstenol) and prostancyclin analogs are prohibited since this class of drugs shares the same mechanism of action with aCT-293987.

During the study, the patient will be asked to come to the clinic for scheduled visits starting with Visit 1, and then again after 4 weeks, 8 weeks, 16 weeks (for patients in the uptitration period of study drug dose only) , 6 months, and then every 6 months until the end of the study. The investigator will also call the patient at regular intervals to follow their general health. Patients in the uptitration period of will be called every week during the first 2 months and all patients will be called at week 12 and every 3 months between the 6-monthly visits.

Study treatment for each patient lasts from his/her Visit 1 date until the end of the trial i.e., until whichever of the following occurs first: (i) the approval of aCT-293987 in this indication is obtained in the patient's country, (ii) the sponsor decides to stop study aC 065a303/GRiPHon oL, or (iii) the patient, or the investigator decide to discontinue study drug.

Participant Eligibility

1.Signed informed consent prior to initiation of any study-mandated procedure.
2. Patients who have completed the double-blind study, AC-065A302/GRIPHON as
scheduled per protocol (i.e., treated until unblinding of the study),
or Patients who have experienced a morbidity event (confirmed by the CEC) during
study AC-065A302/GRIPHON, or Patients experiencing a worsening of PAH during the Treatment Extension period of AC-065A302/GRIPHON and for whom a written approval to roll over into this study has been obtained from the sponsor.
3. Women of child-bearing potential included in study AC-065A303 must use a reliable
method of contraception (with a failure rate of less than 1% per year) until 1 month
after study drug discontinuation.