IMPAHCT

Study AV-101-002 is a Phase 2b/3 study design where recruitment of subjects will continue as the study progresses from Phase 2b to Phase 3 but the Phase 2b and 3 datasets will be kept separate. The objective of the study is to establish an optimal dose based primarily upon the change in PVR assessed by right heart catheterization (RHC) and the safety and tolerability of AV-101 as evaluated in the Phase 2b Part of the study. The optimal dose will be taken into the Phase 3 Part of the study where the placebo-corrected change in 6MWD after 24 weeks of treatment will be used as the primary endpoint. Except for PVR and 6MWD, all secondary endpoints will be similar across the Phase 2b and Phase 3 Parts of the study including NT-proBNP, multi-component improvement score, WHO Functional Class (FC), clinical worsening, REVEAL Lite 2 risk score, Quality of life (QoL), transthoracic echocardiogram (echo) parameters, and safety and tolerability. All subjects will be given the opportunity to enter into a blinded Follow-up Long-Term extension (LTE) study (IMPAHCT-FUL; Study AV-101-003) on completion of the placebo-controlled parts of Study  AV-101 Protocol AV-101-002 FINAL  

AV-101-002. Subjects that were on placebo in Phase 2b and entering the LTE study will be re-randomized to one of the 3 active doses until such time as the optimal dose has been selected. Once the optimal dose has been selected, all subjects will be transitioned to the optimal dose while they continue in the LTE.

Inclusion Criteria

1. World Health Organization (WHO) Functional Class II, III or IV symptoms

    

2. Male or female between 18 and 75 years of age inclusive at the Screening Visit.

    

3. Must have a resting arterial oxygen saturation (SaO2) ≥ 90%, with or without supplemental oxygen, as measured by pulse oximetry at the Screening Visit.

Exclusion Criteria

1. Taking warfarin (or any vitamin K antagonists), direct oral anticoagulant (DOAC) therapy, or dual antiplatelet therapy within 2 weeks prior to Day 1/Randomization
2. Pulmonary hypertension (PH) belonging to Groups 2 to 5 of the 2018 NICE classification

    

3. Left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant ischemic, mitral or aortic valve disease, or constrictive heart disease, in the opinion of the Investigator

 

Study Requirements

Patients will come to the clinic every 4 weeks for 24 weeks. The length of participation will be 24 weeks however it will be possible for patients to participate in a long-term extension study. Patients will have about 7 tablespoons of blood drawn to assess general health and monitoring of heart function. Patients will also have 2 teaspoons of blood drawn from a needle in vein and urine collected for laboratory tests. There are no CT scans, MRI or x-rays required as study procedures.