NCT03782818: OPTION

Olaparib for PAH: a Multicenter Clinical Trial

Terminated Phase 1, PHASE2 Last updated 12 February 2025

What this trial tests

Phase 1, PHASE2 trial testing Olaparib in Pulmonary Arterial Hypertension in 17 participants. Terminated before completion.

Timeline

20 November 2019

Primary endpoint
31 October 2024

31 October 2024

Quick facts

Lead sponsor	Laval University
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	17
Start date	20 November 2019
Primary completion	31 October 2024
Estimated completion	31 October 2024
Sites	3 locations 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 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.

Publications & conference data

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

1. Novel insights on the pulmonary vascular consequences of COVID-19.
   Potus F, Mai V, Lebret M, Malenfant S, et al · · 2020 · cited 113× · PMID 32551862 · DOI 10.1152/ajplung.00195.2020
2. 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
3. Approaches to treat pulmonary arterial hypertension by targeting BMPR2: from cell membrane to nucleus.
   Dunmore BJ, Jones RJ, Toshner MR, Upton PD, et al · · 2021 · cited 38× · PMID 33399862 · DOI 10.1093/cvr/cvaa350
4. New Drugs and Therapies in Pulmonary Arterial Hypertension.
   Shah AJ, Beckmann T, Vorla M, Kalra DK. · · 2023 · cited 36× · PMID 36982922 · DOI 10.3390/ijms24065850
5. PARP1-PKM2 Axis Mediates Right Ventricular Failure Associated With Pulmonary Arterial Hypertension.
   Shimauchi T, Boucherat O, Yokokawa T, Grobs Y, et al · · 2022 · cited 35× · PMID 35540097 · DOI 10.1016/j.jacbts.2022.01.005
6. Pharmacology of Pulmonary Arterial Hypertension: An Overview of Current and Emerging Therapies.
   Spaczyńska M, Rocha SF, Oliver E. · · 2020 · cited 22× · PMID 32832865 · DOI 10.1021/acsptsci.0c00048
7. Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.
   Zolty R. · · 2021 · cited 20× · PMID 34429666 · DOI 10.2147/jep.s236743
8. PARPs and ADP-Ribosylation in Chronic Inflammation: A Focus on Macrophages.
   Santinelli-Pestana DV, Aikawa E, Singh SA, Aikawa M. · · 2023 · cited 14× · PMID 37513811 · DOI 10.3390/pathogens12070964