Apabetalone for Pulmonary Arterial Hypertension

(APPROACH-2 Trial)

Overseen By Pascale Blais-Lecours, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Must be taking: Vasoactive therapy

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: HIV, Portal hypertension, Lung diseases, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 37

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, apabetalone, to determine if it can improve symptoms and enhance heart and lung function in people with pulmonary arterial hypertension (PAH). Researchers aim to assess how apabetalone, when added to existing treatments, impacts exercise capacity and overall health. The trial will compare apabetalone to a placebo (a pill with no active medicine) to understand its true effects. Individuals with PAH who have stable symptoms and have been on consistent treatment for at least three months might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial requires a 2-week period without taking strong CYP3A inhibitors (a type of medication) before starting apabetalone. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that apabetalone is likely to be safe for humans?

Research has shown that apabetalone, a treatment being tested for pulmonary arterial hypertension (PAH), is generally safe. Studies have found that this drug, which blocks a protein called BRD4, is well-tolerated by patients. While specific details about side effects in humans are not provided, the overall results suggest it is safe to use. This is encouraging for those considering joining the trial. Apabetalone is in the clinical development stage, indicating it has already passed some safety tests in earlier research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PAH?

Apabetalone is unique because it targets BET proteins, which play a role in inflammation and cardiovascular disease, setting it apart from other treatments for pulmonary arterial hypertension (PAH) that typically focus on vasodilation or endothelin receptor antagonism. This new mechanism of action could offer benefits by addressing underlying disease processes rather than just symptom management. Researchers are excited about apabetalone's potential to provide a novel approach to managing PAH, potentially improving outcomes for patients who do not respond well to existing therapies like prostacyclins, PDE5 inhibitors, or endothelin receptor antagonists.

What evidence suggests that apabetalone might be an effective treatment for pulmonary arterial hypertension?

Research has shown that apabetalone, a type of medication, may help treat pulmonary arterial hypertension (PAH). Animal studies found that apabetalone can reverse harmful changes in the blood vessels of the lungs. Specifically, it helps control excessive cell growth and resistance to cell death, which can worsen PAH. Additionally, apabetalone has been associated with fewer cases of heart failure and hospital visits in other heart-related conditions. In this trial, participants will receive either apabetalone or a placebo to evaluate its effectiveness as a treatment for PAH. These findings suggest it could be a helpful additional treatment for PAH. ^{1 2 3 4 6}

Who Is on the Research Team?

Steeve Provencher, MD

Principal Investigator

IUCPQ-UL

Pascale Blais-Lecours, PhD

Principal Investigator

IUCPQ-UL

Are You a Good Fit for This Trial?

Adults aged 18-75 with Pulmonary Arterial Hypertension (PAH) who are stable on current PAH medication for at least 3 months can join. They must be able to walk at least 150 meters and have a life expectancy of more than 28 weeks. Participants need normal organ function, not be pregnant or breastfeeding, and agree to use contraception if necessary.

Inclusion Criteria

Your body mass index (BMI) is between 18 and 40.

My pulmonary arterial hypertension is due to genetics, drugs, toxins, or related to a heart defect that was corrected over a year ago.

I am postmenopausal, sterilized, using contraception, or not engaging in activities that could lead to pregnancy.

Exclusion Criteria

My pulmonary hypertension is not caused by left heart diseases, lung diseases, chronic blood clots, or multiple factors.

Your doctor thinks you may not live for more than 1 year because of other health issues.

I have severe lung disease that affects my breathing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-treatment

A 4-week pre-treatment phase to ensure patients are on stable doses of PAH medication

4 weeks

Regular monitoring visits

Treatment

Participants receive apabetalone 100mg BID or placebo for 24 weeks

24 weeks

Baseline, week 8, and week 24 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End-of-study visit at week 28

What Are the Treatments Tested in This Trial?

Interventions

• Apabetalone

Trial Overview The trial is testing the effectiveness of Apabetalone as an additional treatment for PAH over a period of 24 weeks. It will compare changes in pulmonary vascular resistance (PVR) between those taking Apabetalone and those given a placebo while continuing their usual PAH therapy.

How Is the Trial Designed?

Group I: Apabetalone Active Control 1 Intervention

100mg BID, 24-week (168±3 days) Treatment Period.

Group II: Placebo Placebo Group 1 Intervention

24-week (168±3 days) period.

Who Is Running the Clinical Trial?

Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Lead Sponsor

Trials

26

Recruited

6,300+

Laval University

Lead Sponsor

Trials

439

Recruited

178,000+

Resverlogix Corp

Industry Sponsor

Trials

13

Recruited

3,700+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03655704

Apabetalone for Pulmonary Arterial Hypertension: a Pilot ... The overall HYPOTHESIS is that BRD4 inhibition with apabetalone is a safe and effective therapy for PAH. Detailed Description. In line with most pilot and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6888659/

EpiHope for the Treatment of Pulmonary Arterial ... This study provides convincing data, obtained both in vitro and in vivo, indicating that apabetalone normalized the hyperproliferative, apoptosis-resistant and ...

3. atsjournals.org atsjournals.org/doi/10.1164/rccm.202109-2182LE

BET Protein Inhibition for Pulmonary Arterial Hypertension Apabetalone, a clinically available BRD2–4 antagonist, was shown to reverse PA remodeling in diverse PAH rat models, as well as to support the pressure-loaded ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04915300?term=APABETALONE&rank=2

Apabetalone for Pulmonary Arterial Hypertension Moreover, long-term survival on PAH-specific also therapy remains poor in the modern era, with a yearly mortality rate of 15 % in incident idiopathic PAH. The ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11934121/

The Use of Apabetalone in Reducing Cardiovascular ... A meta-analysis of RCTs (n=3,223) demonstrated that apabetalone significantly reduced MACE and hospitalisation for heart failure compared to ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04915300/apabetalone-for-pulmonary-arterial-hypertension

Apabetalone for Pulmonary Arterial Hypertension The primary objective of the study is to assess the efficacy of apabetalone as evaluated by the change in PVR over a period of 24 weeks compared ...