Olaparib for PAH: a Pilot Study

Sponsor
Laval University
Study ID
NCT03251872
Phase
EARLY_PHASE1
Status
Terminated

Conditions

  • Pulmonary Arterial Hypertension

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

Study Details

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 industry-sponsored clinical research on PARP1 inhibitor is currently entirely cancer-oriented. Nonetheless, AstraZeneca Canada accepted to support an early phase clinical trial through in-kind contribution, but the support from foundations and federal agencies is critical to catalyze early-stage development of PARP1 inhibitors for other indications, especially for orphan diseases. A CIHR Project Scheme grant will thus be submitted on September 15 2017, proposing a Phase 1, followed by a Phase 2 trial that will be conducted in recognized PAH programs throughout Canada. At this stage, however, we propose a pilot study to assess the feasibility of the proposed trials in the PAH population. The overall HYPOTHESIS is that PARP1 inhibition with olaparib is a safe and effective therapy for PAH. The primary objective of the study is to confirm feasibility, to support the safety of using olaparib in PAH patients, and precise the sample size of the coming Phase 1B trial. The feasibility of the comprehensive patient phenotyping that will be proposed within the phase 1B trial will thus be assessed, in addition to adverse events and efficacy signals. \*\*\*OPTION pilot trial was merged with the new OPTION multicenter trial (NCT03782818)\*\*\*

Key Dates

Start date
Oct 25, 2018
Status verified
Aug 2020
Primary completion
Dec 1, 2019
Completion
Dec 1, 2019

Study Design

Enrollment
6 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Drug: Olaparib
    Olaparib up to 400 mg BID (100 to 400 mg) for 16 weeks

Primary Outcome Measure

Change in pulmonary vascular resistance (PVR) at week 16 [ Time Frame: 16 weeks ]

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