Olaparib for Pulmonary Arterial Hypertension (OPTION Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen BySteeve Provencher, MD, MSc

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Laval University

No Placebo Group

Approved in 2 jurisdictions

Trial Summary

What is the purpose of this 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.

Eligibility Criteria

This trial is for adults with Pulmonary Arterial Hypertension (PAH) who are stable on current PAH therapy, have a specific range of blood pressure and organ function, and can commit to contraception. Excluded are those recently in other trials, with certain diseases like liver cirrhosis or cancer, uncontrolled medical issues, or unable to take oral meds.

Inclusion Criteria

I will use protection during sex for 3 months after my last olaparib dose.

My heart or lung condition mildly or moderately affects my daily activities.

I am postmenopausal or cannot become pregnant.

My PAH is caused by genetics, drugs, toxins, or is related to a connective tissue disease.

I can walk 150 meters or more without stopping, twice.

Exclusion Criteria

I am not taking strong or moderate CYP3A inhibitor medications.

I have 3 or more risk factors for a specific type of heart failure.

I have had a bacterial infection in the last 30 days.

I have not had major surgery in the last 2 weeks.

I have liver problems but not related to right ventricle failure.

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

I am not taking any strong or moderate drugs that affect liver enzymes.

I have been diagnosed with high blood pressure.

I have had a bone marrow or cord blood transplant in the past.

I have a history of cancer.

I do not have any serious, uncontrolled health issues or infections.

I have had a condition where my lymphocytes grow abnormally.

I cannot take pills by mouth or have stomach issues that affect medication absorption.

I have had a severe spike in blood pressure before.

I have a type of high blood pressure that affects the arteries in my lungs.

I have severe lung disease that affects my breathing.

I have active hepatitis B or C.

I have never been treated with a PARP inhibitor like Olaparib.

Participant Groups

The study tests Olaparib's safety in treating PAH. It's an early-phase trial aiming to see if the drug that helps treat ovarian cancer by protecting against DNA damage could also benefit PAH patients. Participants will be monitored for both safety and initial signs of effectiveness.

1Treatment groups

Experimental Treatment

Group I: OlaparibExperimental Treatment1 Intervention

After a 4-week pre-treatment phase to ensure that patients are on stable doses of PAH medication, patients will be given progressive doses of olaparib up to 300 mg BID for 24 weeks.

Olaparib is already approved in European Union, United States for the following indications:

🇪🇺 Approved in European Union as Lynparza for: