Pulmonary Arterial Hypertension Clinical Trial
Official title:
Olaparib for Pulmonary Arterial Hypertension: a Multicenter Clinical Trial
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.
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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT04076241 -
Effects of Adding Yoga Respiratory Training to Osteopathic Manipulative Treatment in Pulmonary Arterial Hypertension
|
N/A | |
| Completed |
NCT05521113 -
Home-based Pulmonary Rehabilitation With Remote Monitoring in Pulmonary Arterial Hypertension
|
||
| Recruiting |
NCT04972656 -
Treatment With Ambrisentan in Patients With Borderline Pulmonary Arterial Hypertension
|
N/A | |
| Completed |
NCT04908397 -
Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension
|
Phase 1 | |
| Active, not recruiting |
NCT03288025 -
Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE)
|
N/A | |
| Completed |
NCT01959815 -
Novel Screening Strategies for Scleroderma PAH
|
||
| Recruiting |
NCT04266197 -
Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 2B Study
|
Phase 2 | |
| Active, not recruiting |
NCT06092424 -
High Altitude (HA) Residents With Pulmonary Vascular Diseseases (PVD), Pulmonary Artery Pressure (PAP) Assessed at HA (2840m) vs Sea Level (LA)
|
N/A | |
| Enrolling by invitation |
NCT03683186 -
A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
|
Phase 3 | |
| Terminated |
NCT02060487 -
Effects of Oral Sildenafil on Mortality in Adults With PAH
|
Phase 4 | |
| Terminated |
NCT02253394 -
The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
|
Phase 4 | |
| Withdrawn |
NCT02958358 -
FDG Uptake and Lung Blood Flow in PAH Before and After Treatment With Ambrisentan
|
N/A | |
| Terminated |
NCT01953965 -
Look at Way the Heart Functions in People With Pulmonary Hypertension (PH) Who Have Near Normal Right Ventricle (RV) Function and People With Pulmonary Hypertension Who Have Impaired RV Function. Using Imaging Studies PET Scan and Cardiac MRI.
|
Phase 2 | |
| Unknown status |
NCT01712997 -
Study of the Initial Combination of Bosentan With Iloprost in the Treatment of Pulmonary Hypertension Patients
|
Phase 3 | |
| Not yet recruiting |
NCT01649739 -
Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
|
Phase 4 | |
| Withdrawn |
NCT01723371 -
Beta Blockers for Treatment of Pulmonary Arterial Hypertension in Children
|
Phase 1/Phase 2 | |
| Completed |
NCT01548950 -
Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension
|
N/A | |
| Completed |
NCT01165047 -
Nitric Oxide, GeNO Nitrosyl Delivery System
|
Phase 2 | |
| Completed |
NCT00902174 -
Imatinib (QTI571) in Pulmonary Arterial Hypertension
|
Phase 3 | |
| Completed |
NCT00942708 -
Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension
|
Phase 2 |