A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension

NCT ID: NCT03492177

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-23
• Study Completion Date: 2026-12-31

Brief Summary

The purpose of this study to confirm the selexipag starting dose(s), selected based on pharmacokinetic (PK) extrapolation from adults, that leads to similar exposure as adults doses in children from greater than or equal to (>=) 2 to less than (˂) 18 years of age with Pulmonary Arterial Hypertension (PAH), by investigating the PK of selexipag and its active metabolite ACT-333679 in this population.

Detailed Description

The selection of the starting dose for pediatric participants is based on the PK extrapolation from adults, taking into account the children body weight category, in order to lead to an exposure similar to that in adult PAH participants at a starting dose of 200 micrograms (mcg). As in adults, selexipag will be up-titrated to the individual maximum tolerated dose (iMTD) during the first 12 weeks. Approximately 60 participants will be enrolled in 3 different age cohorts to obtain at least 45 participants with evaluable PK profiles: Cohort 1: >= 12 to < 18 years of age, Cohort 2: >= 6 to < 12 years of age, Cohort 3: >= 2 to < 6 years of age. In each age cohort the starting dose will depend on the body weight. Enrollment will start with both Cohort 1 and Cohort 2. After completion of PK assessments in at least 15 participants from Cohort 1 at Week 12, a first interim analysis will be conducted to establish the dose-exposure relationship using a population PK model. The PK data from any participants in Cohort 2 who have completed their PK assessments at this time will be included in this first interim analysis. Results of this model-based analysis will be used to confirm or adjust the selexipag doses initially selected. Enrollment of Cohort 3 (children >= 2 to < 6 years of age) will start once the appropriate doses have been confirmed in a second interim analysis of PK data from Cohorts 1 and 2, and if there is no safety concern based on review by an Independent Data Monitoring Committee (IDMC).

Conditions

Pulmonary Arterial Hypertension

Keywords

Pediatric

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

open label selexipag

The first dose of selexipag (Uptravi) will be administered in the evening of Day 1 and will be based on the body weight. Thereafter selexipag will be administered twice daily (morning and evening). Selexipag will be up-titrated during the first 12 weeks, with weekly increments equal to the starting dose until the participants reach their individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline weight category is achieved (which will be 8-fold of the corresponding starting dose). Up-titration is followed by a stable maintenance treatment period from Week 12 to Week 16, at the maximum tolerated dose. Thereafter, participants will be treated with selexipag as long as the treatment is beneficial to the participants, as per investigator's decision.

Group Type: EXPERIMENTAL

selexipag (Uptravi)

Intervention Type: DRUG

Film-coated tablets for oral administration

Interventions

selexipag (Uptravi)

Film-coated tablets for oral administration

Intervention Type: DRUG

Other Intervention Names

ACT-293987; JNJ-67896049

Eligibility Criteria

Inclusion Criteria

• Signed and dated informed consent by the parent(s) or Legally authorized representative(s) AND assent from developmentally capable children
• Males or females between greater than or equal to (>=) 2 and less than (<) 18 years of age with weight >= 9 kilograms (kg)
• Pulmonary arterial hypertension (PAH) diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before participant's enrollment
• PAH with one of the following etiologies:

• idiopathic (iPAH),
• heritable (hPAH),
• associated with congenital heart disease (CHD): PAH with co-incidental CHD; post-operative PAH (persisting/ recurring/ developing >= 6 months after repair of CHD)
• Drug or toxin-induced
• PAH associated with HIV
• PAH associated with connective tissue disease
• Word Health Organization functional class (WHO FC) II to III
• Participants treated with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor provided that the treatment dose(s) has been stable for at least 3 months prior to enrollment, or participants who are not candidates for these therapies
• Females of childbearing potential must have a negative pregnancy test at Screening and at Enrollment, and must agree to undertake monthly pregnancy tests, and to use a reliable method of contraception (if sexually active) from screening up to study drug discontinuation plus 30 days (EOS)

Exclusion Criteria

• Participants with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis
• Participants with PAH associated with Eisenmenger syndrome
• Participants with moderate to large left-to-right shunts
• Participants with cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, univentricular heart or pulmonary atresia with ventricular septal defect, as well as Participants with Fontan-palliation
• Participants with pulmonary hypertension due to lung disease
• Previous treatment with Uptravi (selexipag) within 2 weeks prior to enrollment
• Participants having received prostacyclin (epoprostenol) or prostacyclin analogs (that is, treprostinil, iloprost, beraprost) within 2 months prior to enrollment or are scheduled to receive any of these compounds during the trial
• Treatment with another investigational drug within 4 weeks prior to enrollment
• History, or current suspicion of intussusception or ileus or gastrointestinal obstruction as per investigator's judgment
• Uncontrolled thyroid disease as per investigator judgment
• Hemoglobin or hematocrit < 75 percentage (%) of the lower limit of normal range
• Known severe or moderate hepatic impairment
• Clinical signs of hypotension that in the investigator's judgment would preclude initiation of a PAH-specific therapy
• Participants with severe renal insufficiency
• Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Catherine Boisson

Role: STUDY_DIRECTOR

Actelion

Locations

Children'S Hospital Cardiac Care Center University Of Colorado

Aurora, Colorado, United States

University of Iowa Hospital

Iowa City, Iowa, United States

Seattle Children's Hospital

Seattle, Washington, United States

State Institution Republican Scientific And Practical Center For Pediatric Surgery

Minsk, , Belarus

Health Institution 4Th City Children'S Clinical Hospital

Minsk, , Belarus

UZ Gent

Ghent, , Belgium

Centre Hospitalier Sainte Justine

Montreal, Quebec, Canada

Beijing Anzhen Hospital

Beijing, , China

Shanghai Childrens Medical Center

Shanghai, , China

CHU Arnaud de Villeneuve

Montpellier, , France

Hôpital Necker - Enfants Malades

Paris, , France

Chu Hopital Des Enfants

Toulouse, , France

Universitätsklinikum Freiburg Zentrum

Freiburg im Breisgau, , Germany

Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály

Budapest, , Hungary

Schneider Children's Medical Center

Petach Tikvah, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Sarawak General Hospital

Kota Samarahan, , Malaysia

Institut Jantung Negara (National Heart Institute)

Kuala Lumpur, , Malaysia

Wojewodzki Szpital Specjalistyczny We Wroclawiu

Wroclaw, , Poland

Kazan State Medical University

Kazan', , Russia

Federal State Budget Scientific Institution

Kemerovo, , Russia

Moscow Scientific Research Institute For Pediatrics And Childrens Surgery Of Rosmedtechnologies

Moscow, , Russia

Saint Petersburg State Pediatric Medical University

Saint Petersburg, , Russia

Federal State Budgetary Institution

Saint Petersburg, , Russia

Samara Regional Clinical Cardiological Dispensary

Samara, , Russia

Univerzitetska Dečja Klinika

Belgrade, , Serbia

Institut Za Zdravstvenu Zastitu Majke I Deteta Srbije Dr Vukan Cupic

Belgrade, , Serbia

National Cheng Kung University Hospital

Tainan, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Municipal Enterprise Of The Dnipropetrovsk Regional Council

Dnipro, , Ukraine

State Institution Of The Ministry Of Health Of Ukraine

Kiev, , Ukraine

Lviv Regional Clinical Hospital

Lviv, , Ukraine

Municipal Institution Of The Zaporizhzhya Regional Council

Zaporizhzhya, , Ukraine

Great Ormond Street Hospital

London, , United Kingdom

Countries

Romania; United States; Belarus; Belgium; Canada; China; France; Germany; Hungary; Israel; Malaysia; Poland; Russia; Serbia; Taiwan; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AC-065A203

Identifier Type: OTHER

Identifier Source: secondary_id

2022-503042-42-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

AC-065A203

Identifier Type: -

Identifier Source: org_study_id