Ignite Creation Date:
2025-12-25 @ 5:01 AM
Ignite Modification Date:
2025-12-26 @ 4:02 AM
Study NCT ID:
NCT03782818
Status:
TERMINATED
Last Update Posted:
2025-02-12
First Post:
2018-12-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Olaparib for PAH: a Multicenter Clinical Trial
Sponsor:
Laval University
Organization:
Study Overview
Official Title:
Olaparib for Pulmonary Arterial Hypertension: a Multicenter Clinical Trial
Status:
TERMINATED
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The recruitment was stopped on October 31st 2024 due to limited recruitment within the last year, as well as the end of funding (Spring 2025).
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OPTION
Brief Summary:
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.
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.
Detailed Description:
Overall, 20 well-characterized PAH patients that have been stable for \>4 months on standard PAH-therapies, as per guidelines will be recruited. The initial Health Canada approval will be obtained. Olaparib will be provided by AstraZeneca Canada, but AZ had no input into the trial design and will not be involved in the conduct of the trial, analysis, interpretation of the results or the final manuscript.
A 4-week pre-treatment phase will allow ensuring that patients are on stable doses of PAH medication.
Given that PAH is a chronic disease and that patients may be at higher risk for drug-related adverse events (e.g. anemia), olaparib will be started at low-dose (100mg BID), then up-titrated weekly by 100mg BID up to 200mg BID (n=5, group 1) or 300mg BID (n=15, group 2) for a total treatment duration (including the up-titration phase) of 24 weeks. Using 100mg and 150mg tablets will allow minimizing the number of tablets taken (e.g. 2 x 150mg tablets BID) or adjusting the dose in case of drug-related adverse events (e.g. 250mg BID using 100mg and 150mg tablets).
Patients will be regularly followed to assess whether side effects are observed and whether olaparib can be up-titrated.
At baseline and week 24, a cardiac catheterization will assess changes in pulmonary hemodynamics and RV function.
An end-of-study visit is planned at week 28 week.
A 4-week pre-treatment phase will allow ensuring that patients are on stable doses of PAH medication.
Given that PAH is a chronic disease and that patients may be at higher risk for drug-related adverse events (e.g. anemia), olaparib will be started at low-dose (100mg BID), then up-titrated weekly by 100mg BID up to 200mg BID (n=5, group 1) or 300mg BID (n=15, group 2) for a total treatment duration (including the up-titration phase) of 24 weeks. Using 100mg and 150mg tablets will allow minimizing the number of tablets taken (e.g. 2 x 150mg tablets BID) or adjusting the dose in case of drug-related adverse events (e.g. 250mg BID using 100mg and 150mg tablets).
Patients will be regularly followed to assess whether side effects are observed and whether olaparib can be up-titrated.
At baseline and week 24, a cardiac catheterization will assess changes in pulmonary hemodynamics and RV function.
An end-of-study visit is planned at week 28 week.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: