Active Clinical Trials
A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
ADVANCED OUTCOMES, APD811-301, A StuDy eVAluatiNg the EffiCacy and Safety of RalinEpag To Improve Treatment OUTCOMES in PAH Patients
Study APD811-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.
Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Males or females aged 18-75 years, inclusive.
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Diagnosis of symptomatic WHO Group 1
Has had a right heart catheterization (RHC) performed at or within 365 days of Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH
Has WHO/ NYHA functional class II to IV symptoms.
If on PAH-specific background therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or an agent acting on the nitric oxide (NO) pathway, a phosphodiesterase type 5 (PDE5) inhibitor or a soluble guanylate cyclase (sGC) stimulator. Subjects may be naïve to PAH-specific treatments.
Stable is defined as no change in dose or regimen within 90 days of Screening and for the duration of the study.
Subjects may be on 1 agent active in the NO pathway, i.e., either a PDE5 inhibitor or an sGC stimulator at stable dose (but not both).
If the subject's disease-specific PAH therapy does not include a PDE5 inhibitor, the use of PDE5 inhibitor as needed for erectile dysfunction (ED) is permitted as long as the subject has not taken a dose within 48-hours of any Baseline or study related efficacy assessment. In addition, the subject must not take more than 8 sildenafil tablets, 6 vardenafil, or 4 tadalafil tablets per month for ED.
Has a 6MWD of ≥50 meters on two consecutive tests, within 15% of each other, preferably performed on different days during Screening. If both tests are done on the same day, then they must be completed >4 hours apart.
Both male and female subjects agree to use a medically acceptable method of contraception throughout the entire study period from informed consent through to the Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process (i.e., actively attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) during the study and for 30 days after the last dose of IMP. Medically acceptable methods of contraception include the following:
oral, implantable, or injectable contraceptives (starting ≥60 days before dosing) and diaphragm with vaginal spermicide, cervical cap with vaginal spermicide, or male condom; male condom and partner using diaphragm with vaginal spermicide or cervical cap with vaginal spermicide;
standard intrauterine device (IUD; e.g., Copper T 380A IUD), intrauterine system (IUS; e.g., LNg 20 IUS - progesterone IUD), progesterone implant, or tubal sterilization (≥180 days after surgery);
post vasectomy and male condom, partner using diaphragm with spermicide, cervical cap with spermicide, estrogen and progesterone oral contraceptives ("the pill"), estrogen and progesterone transdermal patch, vaginal ring, or progesterone injection. Women who are surgically sterile or postmenopausal for at least 12 months are not considered to be of childbearing potential. If of childbearing potential, female partners of male study participants should agree to utilize medically acceptable methods of contraception for the duration of study participation.
Body weight <40 kg.
Body mass index (BMI) ≥40 kg/m2.
Group 2 to 5 pulmonary hypertension.
PAH diagnosis ≥5 years at Screening.
For subjects with HIV-associated PAH, any of the following:
concomitant active opportunistic infections within 180 days of Screening.
detectable viral load at Screening.
cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Screening.
changes in antiretroviral regimen within 90 days of Screening.
Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction at Screening:
BMI >30 kg/m2.
Diabetes mellitus of any type.
Significant coronary artery disease, i.e., any of the following:
More than 50% stenosis in a coronary artery (by coronary angiography)
Previous myocardial infarction
Previous or planned coronary artery bypass grafting and/or coronary artery stenting
Left atrial volume index (LAVi) >30 mL/m2.
Diagnosis of Down syndrome. Subjects with Down syndrome are excluded due to the high potential of undiagnosed or poorly managed obstructive sleep apnea in this population.
Malignancy within 5 years of Screening, with the exception of localized non-metastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix excised with curative intent.
Recent history (i.e., within 1 year prior to Screening) of alcohol or drug abuse.
Initiation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.