NCT03655704: APPRoAcH-p

Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study

Completed EARLY_PHASE1 Last updated 25 April 2022

What this trial tests

EARLY_PHASE1 trial testing Apabetalone in Pulmonary Arterial Hypertension in 7 participants. Completed in 13 December 2021.

Timeline

22 August 2019

Primary endpoint
15 October 2021

13 December 2021

Quick facts

Lead sponsor	Steeve Provencher
Phase	EARLY_PHASE1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	screening
Enrollment	7
Start date	22 August 2019
Primary completion	15 October 2021
Estimated completion	13 December 2021
Sites	2 locations across Canada

Drugs / interventions tested

• Apabetalone — full drug profile →

Conditions studied

• Pulmonary Arterial Hypertension — all drugs for Pulmonary Arterial Hypertension →

Sponsor

Steeve Provencher

Who can join

Adults 18 to 75, any sex, with Pulmonary Arterial Hypertension. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials.
   Shi Y, Zhang H, Huang S, Yin L, et al · · 2022 · cited 233× · PMID 35752619 · DOI 10.1038/s41392-022-01055-2
2. Epigenetics-targeted drugs: current paradigms and future challenges.
   Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
3. BET Epigenetic Reader Proteins in Cardiovascular Transcriptional Programs.
   Borck PC, Guo LW, Plutzky J. · · 2020 · cited 125× · PMID 32324495 · DOI 10.1161/circresaha.120.315929
4. Beyond the Lungs: Systemic Manifestations of Pulmonary Arterial Hypertension.
   Nickel NP, Yuan K, Dorfmuller P, Provencher S, et al · · 2020 · cited 68× · PMID 31513751 · DOI 10.1164/rccm.201903-0656ci
5. Repurposing Medications for Treatment of Pulmonary Arterial Hypertension: What's Old Is New Again.
   Prins KW, Thenappan T, Weir EK, Kalra R, et al · · 2019 · cited 67× · PMID 30590974 · DOI 10.1161/jaha.118.011343
6. Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside.
   Sarno F, Benincasa G, List M, Barabasi AL, et al · · 2021 · cited 49× · PMID 33785068 · DOI 10.1186/s13148-021-01047-z
7. Oxidative Stress and Antioxidative Therapy in Pulmonary Arterial Hypertension.
   Xu D, Hu YH, Gou X, Li FY, et al · · 2022 · cited 45× · PMID 35744848 · DOI 10.3390/molecules27123724
8. The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression.
   Dasgupta N, Arnold R, Equey A, Gandhi A, et al · · 2024 · cited 41× · PMID 39448585 · DOI 10.1038/s41514-024-00172-2