Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study
Status:
Active, not recruiting
Trial end date:
2021-12-01
Target enrollment:
Participant gender:
Summary
The main OBJECTIVE of this proposal is to extend the investigator's preclinical findings on
the role of epigenetics and DNA damage and Bromodomain-Containing Protein 4 (BRD4) inhibition
as a therapy for a devastating disease, pulmonary arterial hypertension (PAH).
There is strong evidence that BRD4 plays a key role in the pathological phenotype in PAH
accounting for disease progression and that BRD4 inhibition can reverse PAH in several animal
models. Intriguingly, coronary artery disease (CAD) and metabolic syndrome are more prevalent
in PAH compared with the global population, suggesting a link between these diseases.
Interestingly, BRD4 is also a trigger for calcification and remodeling processes and
regulates transcription of lipoprotein and inflammatory factors, all of which are important
in PAH and CAD. Apabetalone, an orally available BRD4 inhibitor, is now in a clinical
development stage with a good safety profile.
At this stage, the investigators propose a pilot study to assess the feasibility of a Phase 2
clinical trial assessing apabetalone in the PAH population. The overall HYPOTHESIS is that
BRD4 inhibition with apabetalone is a safe and effective therapy for PAH.