Macitentan for Pulmonary Hypertension

(TOMORROW Trial)

Recruiting at 85 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

165 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Macitentan for treating pulmonary hypertension?

Research shows that Macitentan significantly reduces the risk of worsening symptoms and hospitalizations in patients with pulmonary arterial hypertension. It also improves exercise capacity and quality of life, making it a useful treatment option for this condition. ^{1 2 3 4 5}

Is macitentan safe for humans?

Macitentan has been shown to be generally safe for treating pulmonary hypertension, with studies indicating it reduces hospitalizations and improves quality of life. It has a similar safety profile in real-world use as seen in initial trials, and long-term safety has been supported by multiple studies. ^{5 6 7 8 9}

What makes the drug Macitentan unique for treating pulmonary hypertension?

Macitentan is unique because it is a dual endothelin receptor antagonist (a type of drug that blocks certain proteins that cause blood vessels to narrow) with tissue targeting properties, and it is the only registered treatment for pulmonary arterial hypertension that has been shown to significantly reduce both morbidity and mortality in long-term studies. It also offers the convenience of once-daily oral administration. ^{1 10 11 12 13}

What is the purpose of this trial?

This trial is testing macitentan, a drug that helps lower lung blood pressure, in children with pulmonary arterial hypertension. Macitentan has shown significant effectiveness in improving the condition of patients with pulmonary arterial hypertension.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

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

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

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

Development of macitentan for the treatment of pulmonary arterial hypertension. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Benefits of Macitentan in Patients with Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2023]

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

Safety and tolerability of macitentan in the management of pulmonary arterial hypertension: an update. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Long-term safety of macitentan in patients with pulmonary hypertension: A meta-analysis of randomised controlled trials. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of macitentan for pulmonary hypertension: A meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Safety and Clinical Outcomes of Macitentan in Asian Patients with Pulmonary Arterial Hypertension: A Prospective Multicenter Study. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Macitentan treatment retards the progression of established pulmonary arterial hypertension in an animal model. [2022]

11. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension: extended study results. [2021]

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

Evolution of Patients with Pulmonary Arterial Hypertension Starting Macitentan After the Discontinuation of Other Endothelin-Receptor Antagonists: Results of a Retrospective Study. [2021]