High-Dose Macitentan for PAH

(UNISUS Trial)

Not currently recruiting at 415 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a higher dose of macitentan, a medication, can better prevent serious events or death in people with pulmonary arterial hypertension (PAH), a condition characterized by high blood pressure in the lungs. It compares macitentan at 75 mg to the standard 10 mg dose to determine which is more effective. People with PAH who experience symptoms and can walk at least 50 meters in six minutes might be suitable for this study. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that macitentan is generally safe for people with pulmonary arterial hypertension (PAH). Studies have examined the safety and effectiveness of different doses, specifically 10 mg and 75 mg.

For the 10 mg dose, studies have found that it significantly lowers the risk of PAH worsening, indicating its safety. Current research is exploring whether the 75 mg dose can better prevent serious health issues in people with PAH. Although the 75 mg dose is still under study, no major safety problems have emerged so far.

Overall, macitentan has been safely used at lower doses, and ongoing studies are assessing if the higher dose is equally safe while offering greater effectiveness. ^{1 2 3 4 5}

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

Researchers are excited about high-dose macitentan for pulmonary arterial hypertension (PAH) because it offers a potential boost in efficacy by increasing the dosage beyond what is commonly used. Unlike standard treatments such as lower doses of macitentan, ambrisentan, or bosentan, this study explores using a higher dose of macitentan, which may better inhibit endothelin receptor activity, a key contributor to PAH. This could lead to improved outcomes in managing PAH symptoms and slowing disease progression. Additionally, the trial includes a treatment extension period to assess the long-term benefits and safety of sustained high-dose therapy, promising new insights into optimizing PAH management.

What evidence suggests that macitentan might be an effective treatment for PAH?

Research has shown that macitentan effectively treats pulmonary arterial hypertension (PAH). Studies have found that a 10 mg dose of macitentan can improve exercise ability and slow the disease's progression. In this trial, participants will receive either a 10 mg dose or a higher dose of 75 mg. Early results suggest that the higher dose might be even more effective, potentially delaying serious health issues related to PAH. By blocking certain proteins that tighten blood vessels, macitentan helps blood flow more easily. Overall, both doses of macitentan appear promising in managing PAH symptoms. ^{1 4 5 6 7}

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.

academic.oup.com

academic.oup.com/eurheartj/article-abstract/doi/10.1093/eurheartj/ehac544.1929/6744805

UNISUS study design: a phase 3 superiority study comparing ...

UNISUS study design: a phase 3 superiority study comparing the efficacy, safety, and tolerability of macitentan 75 mg vs macitentan 10 mg in ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8258181/

Results of Macitentan in Japanese Patients With Chronic ...

A study to evaluate efficacy and safety of macitentan 75 mg in inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (MACiTEPH).

3.

mayo.edu

mayo.edu/research/clinical-trials/cls-20520135

An Outcome Study Assessing a 75 Milligrams (mg) Dose ...

The purpose of this study is to demonstrate superiority of macitentan 75 milligrams (mg) in prolonging the time to the first clinical events ...

4.

clinicaltrials.eu

clinicaltrials.eu/trial/study-comparing-the-effectiveness-and-safety-of-macitentan-75-mg-and-10-mg-for-patients-with-pulmonary-arterial-hypertension/

Study Comparing the Effectiveness and Safety of ...

The purpose of the study is to see if the higher dose of Macitentan is more effective in delaying the time to the first serious health event related to PAH.

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04273945

NCT04273945 | Outcome Study Assessing a 75 Milligrams ...

Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension (UNISUS). ClinicalTrials.gov ID NCT04273945.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9402744/

Long-Term Safety, Tolerability and Survival in Patients with ...

A long-term, event-driven, double-blind randomised controlled trial in pulmonary arterial hypertension (PAH), macitentan 10 mg significantly reduced the risk ...

7.

academic.oup.com

academic.oup.com/eurheartj/article/43/Supplement_2/ehac544.1929/6744805

UNISUS study design: a phase 3 superiority study comparing ...

The UNISUS study is the first head-to-head superiority study in PAH, comparing the time to morbidity or mortality (M/M) with macitentan 75 mg vs macitentan 10 ...