Macitentan for Pulmonary Hypertension

(TOMORROW Trial)

No longer recruiting at 109 trial locations

Overseen By Nicole Shipitofsky

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Actelion

Must not be taking: IV prostanoids

Disqualifiers: Portal hypertension, Eisenmenger syndrome, 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

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called macitentan in children with pulmonary arterial hypertension (PAH), a condition characterized by high blood pressure in the lungs. The trial aims to assess the safety and effectiveness of macitentan in improving this condition. It compares macitentan to standard treatments that children might already receive. Children with PAH due to causes like congenital heart disease, Down Syndrome, or connective tissue diseases might be suitable candidates. However, the trial excludes those with certain other conditions, such as severe liver or kidney issues. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on more than two PAH-specific treatments or have used certain medications like IV or SC prostanoids within 4 weeks before starting the trial.

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

Research has shown that macitentan is generally safe and well-tolerated for treating pulmonary hypertension. Studies have found that patients using macitentan experienced few serious side effects, maintaining a good safety record. The treatment results aligned with expectations from earlier research. In a large study, macitentan reduced the risk of health worsening or death in individuals with this condition. Additionally, real-world data from patients in various settings confirm that macitentan is usually well tolerated, making it a promising option for managing pulmonary arterial hypertension (PAH). ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for pulmonary hypertension, which often involves a combination of non-specific treatments and PAH-specific drugs (excluding macitentan), macitentan offers a unique approach. This medication works by specifically targeting endothelin receptors, which play a significant role in the narrowing of blood vessels. By blocking these receptors, macitentan helps to relax and widen the blood vessels, potentially improving blood flow and reducing the strain on the heart. Researchers are excited about macitentan because it could offer more targeted relief with a once-daily oral dose, making it a convenient option, especially for children.

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

Research has shown that macitentan reduces risks associated with pulmonary arterial hypertension (PAH). In studies, macitentan reduced the risk of hospital visits due to PAH by 50% compared to a placebo. It also lowered the likelihood of hospitalization for any reason and extended patients' lives. Macitentan has clearly reduced both illness and death in people with PAH. In this trial, participants will receive either macitentan or standard-of-care treatment. These findings suggest that macitentan can effectively manage pulmonary hypertension. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children under 18 with pulmonary arterial hypertension (PAH), including those with Down Syndrome. They must have a confirmed PAH diagnosis and be in WHO Functional class I to III. Females of childbearing potential need negative pregnancy tests and must use contraception. Participants can't join if they have certain conditions like severe renal insufficiency, are on multiple PAH treatments, or have severe liver impairment.

Inclusion Criteria

I am under 18 years old.

I have been diagnosed with PAH confirmed by a heart catheter test.

Signed informed consent by the parent(s) or legally designated representative and assent from developmentally capable children prior to initiation of any study-mandated procedure

Exclusion Criteria

I haven't taken IV or SC prostanoids in the last 4 weeks, except for a specific test.

I am currently on more than two treatments for pulmonary arterial hypertension.

I have PAH linked to Eisenmenger syndrome or significant heart defects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive macitentan or standard-of-care treatment for pulmonary arterial hypertension

24 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue to receive macitentan in a single-arm extension period

Up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Macitentan

Trial Overview

The study is testing the effects of Macitentan compared to standard care in children with PAH. It's an open-label Phase 3 trial where participants are randomly assigned to either receive Macitentan or continue with their usual treatment while researchers track how well the drug works and its safety.

How Is the Trial Designed?

Group I: Standard-of-care Experimental Treatment 1 Intervention

Standard-of-care as per site's clinical practice which may comprise treatment with pulmonary arterial hypertension (PAH) non-specific treatment and/or up to two PAH-specific medications excluding macitentan and intravenous/subcutaneous (IV/SC) prostanoids.

Group II: Macitentan Experimental Treatment 1 Intervention

Macitentan is administered once daily via oral route. Children less than (\<) 2 years old (y.o.) will be assigned as a cohort to the macitentan group without randomization. The dose will be adjusted to the participant's age (for those \< 2 y.o.) or to the participant's body weight (for those greater than or equal to (\>=) 2 y.o.). single-arm extension period (SAEP) will start at end of core period (EOCP) visit and ends at end of study (EOS) visit.

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

Macitentan, a dual endothelin receptor antagonist, significantly reduces the risk of morbidity and mortality in patients with pulmonary arterial hypertension (PAH) by 45% compared to placebo, particularly benefiting those in WHO functional class II and III.

In the largest and longest trial for PAH to date, macitentan improved patients' exercise capacity, quality of life, and cardiopulmonary hemodynamics, while also demonstrating a favorable safety profile, marking a shift towards long-term outcome-oriented therapy in PAH management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of macitentan for the treatment of pulmonary arterial hypertension. Selej, M., Romero, AJ., Channick, RN., et al.[2016]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40273999/

A real-world comparative effectiveness analysis of ...

Conclusion: Macitentan was associated with a significantly reduced risk of PAH-related and all-cause hospitalization, with lower ICU healthcare ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10632077/

Efficacy and safety of macitentan for pulmonary hypertension

Our purpose of this study is to evaluate the effect and safety of macitentan in the treatment of pulmonary hypertension (PH).

3.

opsumithcp.com

opsumithcp.com/clinical-trials/seraphin-trial/

SERAPHIN Trial | OPSUMIT® (macitentan) HCP

There was a 50% reduction in the risk of PAH-related hospitalization vs placebo in the overall population.†. Kaplan-Meier estimates of risk of first key ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1213917

Macitentan and Morbidity and Mortality in Pulmonary ...

Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study.

5.

resmedjournal.com

resmedjournal.com/article/S0954-6111(25)00174-X/fulltext

A real-world comparative effectiveness analysis of ...

Macitentan was associated with a significantly reduced risk of PAH-related and all-cause hospitalization, with lower ICU healthcare resource utilization, ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36381290/

Real-world experience from the OPsumit® USers Registry ...

Macitentan is well tolerated in a large, diverse population of PAH patients, with overall and hepatic safety profiles consistent with previous macitentan ...

7.

tandfonline.com

tandfonline.com/doi/full/10.1080/03007995.2024.2349733

Real-world effectiveness and safety of macitentan in ...

This study provided real-world evidence on the clinical benefits and good tolerance of macitentan in Chinese patients with PAH treated in routine clinical ...

8.

cdt.amegroups.org

cdt.amegroups.org/article/view/41180/html

Safety and efficacy of the endothelin receptor antagonist ...

Macitentan treatment was well tolerated and was associated with improvements in invasive hemodynamics, longitudinal systolic RV function (TAPSE) and serum NT- ...