NCT03251872: OPTION-p

Olaparib for PAH: a Pilot Study

Terminated EARLY_PHASE1 Last updated 26 August 2020

What this trial tests

EARLY_PHASE1 trial testing Olaparib in Pulmonary Arterial Hypertension in 6 participants. Terminated before completion.

Timeline

25 October 2018

Primary endpoint
1 December 2019

1 December 2019

Quick facts

Lead sponsor	Laval University
Phase	EARLY_PHASE1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	6
Start date	25 October 2018
Primary completion	1 December 2019
Estimated completion	1 December 2019
Sites	1 location across Canada

Drugs / interventions tested

• Olaparib (olaparib) — full drug profile →

Conditions studied

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

Sponsor

Laval University

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 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)\*\*\*

Publications & conference data

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

1. Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives.
   Humbert M, Guignabert C, Bonnet S, Dorfmüller P, et al · · 2019 · cited 924× · PMID 30545970 · DOI 10.1183/13993003.01887-2018
2. Clinical trial design and new therapies for pulmonary arterial hypertension.
   Sitbon O, Gomberg-Maitland M, Granton J, Lewis MI, et al · · 2019 · cited 144× · PMID 30545975 · DOI 10.1183/13993003.01908-2018
3. Notch3 signalling and vascular remodelling in pulmonary arterial hypertension.
   Morris HE, Neves KB, Montezano AC, MacLean MR, et al · · 2019 · cited 85× · PMID 31868216 · DOI 10.1042/cs20190835
4. New and Emerging Therapies for Pulmonary Arterial Hypertension.
   Spiekerkoetter E, Kawut SM, de Jesus Perez VA. · · 2019 · cited 72× · PMID 30216732 · DOI 10.1146/annurev-med-041717-085955
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. 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
7. Pathological Mechanisms and Potential Therapeutic Targets of Pulmonary Arterial Hypertension: A Review.
   Xiao Y, Chen PP, Zhou RL, Zhang Y, et al · · 2020 · cited 34× · PMID 33269111 · DOI 10.14336/ad.2020.0111
8. Transcriptomic analysis of pulmonary artery smooth muscle cells identifies new potential therapeutic targets for idiopathic pulmonary arterial hypertension.
   Gorr MW, Sriram K, Muthusamy A, Insel PA. · · 2020 · cited 32× · PMID 32337710 · DOI 10.1111/bph.15074