Selexipag for Pulmonary Arterial Hypertension

(SALTO Trial)

Recruiting at 146 trial locations

Overseen By Study Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Actelion

Must be taking: Endothelin antagonists, PDE-5 inhibitors

Disqualifiers: Eisenmenger syndrome, Life expectancy <12 months, others

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: Up to 5 years

138 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate whether the addition of selexipag to standard of care treatment delays disease progression in children with Pulmonary Arterial Hypertension (PAH) in comparison to placebo.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you have been on a stable dose of at least one PAH-specific treatment for at least 3 months before starting the study.

Is selexipag safe for humans?

Selexipag is generally considered safe for humans, with a low side-effect profile observed in clinical trials for pulmonary arterial hypertension (PAH). It is well tolerated, with side effects similar to other treatments targeting the same pathway. ^{1 2 3 4 5}

How does the drug selexipag differ from other treatments for pulmonary arterial hypertension?

Selexipag is unique because it is an oral drug that specifically targets the prostacyclin receptor, helping to relax and widen blood vessels in the lungs, which reduces blood pressure. Unlike some other treatments, it is used in combination with other medications to improve outcomes for patients with pulmonary arterial hypertension. ^{3 4 6 7 8}

Research Team

Actelion Clinical Trial

Principal Investigator

Actelion

Eligibility Criteria

This trial is for children aged 2-18 with Pulmonary Arterial Hypertension (PAH) who are already on stable PAH treatment. They must weigh at least 9 kg and have a confirmed diagnosis through right heart catheterization. It's not for those with certain types of PAH, previous selexipag use, life-threatening diseases, or pregnancy.

Inclusion Criteria

I have been on a stable dose of treatment for pulmonary arterial hypertension for at least 3 months.

I have pulmonary arterial hypertension (PAH) and may also have Down syndrome.

My heart condition allows me to perform light to moderate activities.

Exclusion Criteria

I have a serious illness and am expected to live less than a year.

You are allergic or very sensitive to selexipag or its ingredients.

Pregnant, planning to become pregnant, or lactating

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

Treatment

Participants receive either selexipag or placebo with uptitration for 12 weeks followed by a maintenance period until end of treatment

Up to 5 years

Open-label extension

Participants may continue to receive selexipag for an additional 3 years

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Treatment Details

Interventions

• Placebo
• Selexipag

Trial Overview The study tests if adding Selexipag to standard treatments can slow down the progression of PAH in children compared to a placebo. Participants will be randomly assigned to receive either Selexipag or a placebo alongside their current treatment.

Participant Groups

Group I: Selexipag Experimental Treatment 1 Intervention

Participants will receive selexipag based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Selexipag will be uptitrated during the first 12 weeks until the participants reaches the individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline body-weight category is achieved. Uptitration is followed by a maintenance period after Week 12 until end of treatment (EOT), at the maximum tolerated dose.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo based on the body weight on Day 1 and will continue thereafter with twice daily dosing.

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

Selexipag, an oral prostacyclin agonist approved for pulmonary arterial hypertension (PAH), has shown significant efficacy in reducing death and hospitalization rates in PAH patients during the phase 3 GRIPHON study, which involved multiple centers.

While selexipag improved patients' 6-minute walk distance, indicating better symptom management, it did not demonstrate a significant impact on overall mortality, highlighting the need for further studies to fully understand its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies. Ghosh, RK., Ball, S., Das, A., et al.[2018]

A 42-year-old woman with high-risk idiopathic pulmonary arterial hypertension (PAH) showed significant clinical and hemodynamic improvement after being treated with an off-label triple oral combination therapy that included selexipag, a phosphodiesterase-5 inhibitor, and an endothelin receptor antagonist.

This case suggests that oral combination therapies, like the one used in this patient, could be a viable alternative to parenteral prostacyclin analogues for high-risk PAH patients, warranting further investigation in controlled clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront triple oral combination therapy including selexipag in a high-risk patient with idiopathic pulmonary arterial hypertension: a case report. Rossi, S., Pietrangelo, C., Pierdomenico, SD., et al.[2022]

Selexipag is an effective treatment for pulmonary arterial hypertension (PAH), showing significant improvements in pulmonary artery obstruction and right ventricular function in both animal models and clinical trials, including a large study with 1156 patients.

In clinical trials, selexipag demonstrated good tolerability and a significant reduction in the risk of death or complications related to PAH, indicating its potential to prevent disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of Selexipag (Uptravi&#174; tablets), a selective prostacyclin receptor agonist]. Kuwano, K., Kosugi, K., Fuchikami, C., et al.[2021]

References

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

Selexipag for the Treatment of Pediatric Pulmonary Hypertension: A Systematic Review. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies. [2018]

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

Upfront triple oral combination therapy including selexipag in a high-risk patient with idiopathic pulmonary arterial hypertension: a case report. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Selexipag-based triple combination therapy improves prognosis in Chinese pulmonary arterial hypertension patients. [2022]

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

Selexipag: A Review in Pulmonary Arterial Hypertension. [2018]

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

Patient and disease characteristics of the first 500 patients with pulmonary arterial hypertension treated with selexipag in real-world settings from SPHERE. [2022]

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

Disease characteristics, treatments, and outcomes of patients with pulmonary arterial hypertension treated with selexipag in real-world settings from the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry). [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of Selexipag (Uptravi&#174; tablets), a selective prostacyclin receptor agonist]. [2021]