The main OBJECTIVE of this proposal is to extend our preclinical findings on the role of DNA
damage and poly(ADP-ribose) polymerases (PARP) inhibition as a therapy for a devastating
disease, pulmonary arterial hypertension (PAH), to early-phase clinical trials. We, and
others, have published strong evidence that DNA damage accounts for disease progression in
PAH and showed that PARP1 inhibition can reverse PAH in several animal models1.
Interestingly, PARP1 inhibition is also cardioprotective. Olaparib, an orally available PARP1
inhibitor, can reverse cancer growth in animals and humans with a good safety profile, and is
now approved for the treatment of ovarian cancer in Canada, Europe and the USA. The time is
thus right to translate our findings in human PAH.
The primary objective of this Phase 1B study is to confirm the safety of using olaparib in
PAH patients, and precise the sample size of a future Phase 2 trial. In addition to safety,
efficacy signals will thus be assessed.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
Laval University
Collaborators:
AstraZeneca Canadian Institutes of Health Research (CIHR)