High-Dose Macitentan for PAH

(UNISUS Trial)

Recruiting at 341 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Actelion

Disqualifiers: Obesity, Diabetes, Hypertension, Coronary artery disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

935 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing if a higher dose of macitentan can better help patients with pulmonary arterial hypertension by improving blood flow in their lungs. Macitentan has shown promise in helping patients by slowing down the disease and improving their health.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Macitentan for treating pulmonary arterial hypertension (PAH)?

Research shows that Macitentan significantly reduces the risk of PAH-related events and death, improves exercise capacity, and enhances quality of life in patients with PAH. In clinical practice, patients treated with Macitentan showed improvements in walking distance and heart function, with no hospitalizations or deaths reported. ^{1 2 3 4 5}

Who Is on the Research Team?

Actelion Clinical Trials

Principal Investigator

Actelion

Are You a Good Fit for This Trial?

Adults with symptomatic Pulmonary Arterial Hypertension (PAH) in various severity classes, confirmed by specific heart and lung pressure measurements. Eligible participants include those with PAH due to different causes such as genetic factors, drug use, or associated diseases like HIV. They must be able to perform a walking test and not have severe liver issues, certain blood disorders, or significant risk factors for heart failure.

Inclusion Criteria

I can complete a 6-minute walking test.

You have been diagnosed with pulmonary arterial hypertension (PAH) based on specific measurements of your heart and lung pressures.

I have symptoms of severe lung blood pressure in stages II, III, or IV.

Exclusion Criteria

You have three or more factors that increase your risk of heart failure with preserved ejection fraction.

Your hemoglobin level is less than 100 grams per liter at the time of screening.

I have a known liver condition that is moderate to severe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Period

Participants who are ERA-naive or on low doses of certain medications enter a 4-week open-label run-in period with macitentan 10 mg prior to randomization

4 weeks

Double-blind Treatment (DBT) Period

Participants receive macitentan 37.5 mg for 4 weeks and then macitentan 75 mg or 10 mg up to the end of DBT

Up to 4 years

Treatment Extension Period

Participants continue to receive macitentan 75 mg orally for 2 years in an open-label extension

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Macitentan

Trial Overview The trial is testing the effectiveness of a higher dose of Macitentan (75 mg) compared to the standard dose (10 mg) in delaying health deterioration or death in PAH patients. Participants will randomly receive either the high dose, standard dose, an intermediate dose (37.5 mg), or a placebo.

How Is the Trial Designed?

Group I: Macitentan 75 mg + Placebo Experimental Treatment 4 Interventions

Run-in period:Participants who are either ERA-naive or who are receiving a daily dose of macitentan or ambrisentan \<10 mg, or a daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated patients will bypass the run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.DBT Period: participants will receive macitentan 37.5 mg orally for 4 weeks and macitentan 75 mg thereafter up to End of DBT. To maintain the blind, participants will receive macitentan 10 mg-matching placebo up to End of DBT.Treatment Extension Period: After EDBT, participants will continue to receive macitentan 75 mg orally for 2 years. To maintain the blind, participants will receive macitentan 37.5 mg-matching placebo during the 4-week up-titration period.

Group II: Macitentan 10 milligrams (mg) + Placebo Active Control 4 Interventions

Run-in period:Participants who are either endothelin receptor antagonist (ERA)-naïve or who are receiving daily dose of macitentan or ambrisentan less (\<) 10 milligrams (mg), or daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated participants will bypass run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.Double-blind Treatment (DBT) Period:Participants will receive macitentan 10 mg orally up to End of DBT.To maintain blind, participants will receive macitentan 37.5 mg-matching placebo for 4 weeks and macitentan 75 mg-matching placebo thereafter up to DBT.Treatment Extension Period:After EDBT, participants will receive macitentan 37.5 mg once a day (qd) orally for 4 weeks, prior to receiving open-label macitentan 75 mg qd orally for 2 years. To maintain blind, participants will receive macitentan 75 mg-matching placebo during 4-week uptitration.

Who Is Running the Clinical Trial?

Actelion

Lead Sponsor

Trials

192

Recruited

35,500+

Jean-Paul Clozel

Actelion

Chief Executive Officer since 1997

MD from University of Basel

Martine Clozel

Actelion

Chief Medical Officer since 1997

MD from University of Geneva

Published Research Related to This Trial

In a clinical practice setting involving 13 patients with pulmonary arterial hypertension (PAH), 12 months of treatment with macitentan led to significant improvements in functional class and 6-minute walk distance for all patients.

Macitentan treatment also resulted in decreased NT-proBNP levels and improved cardiac imaging parameters, with no hospitalizations or serious adverse events reported during the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macitentan in daily clinical practice: A single centre, 1-year experience. Cadenas-Menéndez, S., Álvarez-Vega, P., Martín-Moreiras, J., et al.[2019]

Citations

1. Spain pubmed.ncbi.nlm.nih.gov

Macitentan in daily clinical practice: A single centre, 1-year experience. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Macitentan: a review of its use in patients with pulmonary arterial hypertension. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety, Tolerability and Survival in Patients with Pulmonary Arterial Hypertension Treated with Macitentan: Results from the SERAPHIN Open-Label Extension. [2022]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Hemodynamic and Histopathologic Benefits of Early Treatment with Macitentan in a Rat Model of Pulmonary Arterial Hypertension. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Macitentan: A Review in Pulmonary Arterial Hypertension. [2017]