NCT03655704

Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Steeve Provencher · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

In line with most pilot and safety studies, this is a two-centre (Quebec and Calgary) open-label trial. A 4-week pre-treatment phase will allow ensuring that patients are on stable doses of medication. Patients will be given doses of apabetalone 100mg BID for 16 weeks. Patients will be regularly followed. At baseline and week 16, a cardiac catheterization and MRI will assess changes in pulmonary hemodynamics and RV function.

Conditions

• Pulmonary Arterial Hypertension

Interventions

Type	Name	Description
DRUG	Apabetalone	A 4-week pre-treatment phase will allow ensuring that patients are on stable doses of medication. Patients will be given doses of apabetalone 100mg BID for 16 weeks. Patients will be regularly followed (Fig.1). At baseline and week 16, a cardiac catheterization and MRI will assess changes in pulmonary hemodynamics and RV function.

Timeline

• Start date: 2019-08-22
• Primary completion: 2021-10-15
• Completion: 2021-12-13
• First posted: 2018-08-31
• Last updated: 2022-04-25

Locations

2 sites across 1 country: Canada