Ignite Creation Date:
2024-05-06 @ 12:32 PM
Last Modification Date:
2024-10-26 @ 1:00 PM
Study NCT ID:
NCT03782818
Status:
RECRUITING
Last Update Posted:
2023-04-18
First Post:
2018-12-17
Brief Title:
Olaparib for PAH a Multicenter Clinical Trial
Sponsor:
Laval University
Organization:
Laval University
Study Overview
Official Title:
Olaparib for Pulmonary Arterial Hypertension a Multicenter Clinical Trial
Status:
RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
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 polyADP-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 eg anemia olaparib will be started at low-dose 100mg BID then up-titrated weekly by 100mg BID up to 200mg BID n5 group 1 or 300mg BID n15 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 eg 2 x 150mg tablets BID or adjusting the dose in case of drug-related adverse events eg 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 eg anemia olaparib will be started at low-dose 100mg BID then up-titrated weekly by 100mg BID up to 200mg BID n5 group 1 or 300mg BID n15 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 eg 2 x 150mg tablets BID or adjusting the dose in case of drug-related adverse events eg 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:
None
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?:
None