Pulmonary Arterial HypertensionPhase 2NCT03492177
A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension
A Phase 2 study testing selexipag (Uptravi) in people with Pulmonary Arterial Hypertension, run by Actelion at 34 sites in 16 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- selexipag (Uptravi)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 34 sitesin 16 countries
- Study dates
- 23 Jul 2018to 31 Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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),
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
34 sites in 16 countries.
34 sites in 16 countries
Russia6 sites
Kazan State Medical University
Kazan', 420059
Scientific and Research Institution of Cardiovascular Diseases Complex Problems
Kemerovo, 650002
Moscow Scientific Research Institute For Pediatrics And Childrens Surgery Of Rosmedtechnologies
Moscow, 125412
Saint Petersburg State Pediatric Medical University
Saint Petersburg, 194100
Almazov National Medical Research Center Of The Ministry Of Health Of The Russian Federation
Saint Petersburg, 197341
Samara Regional Clinical Cardiological Dispensary
Samara, 443070
Ukraine4 sites
Municipal Enterprise Of The Dnipropetrovsk Regional Council
Dnipro, 49070
State Institution Of The Ministry Of Health Of Ukraine
Kiev, 04050
Lviv Regional Clinical Hospital
Lviv, 79010
Municipal Institution Of The Zaporizhzhya Regional Council
Zaporizhzhya, 69063
United States3 sites
Children'S Hospital Cardiac Care Center University Of Colorado
Aurora, Colorado, 80045
University of Iowa Hospital
Iowa City, Iowa, 52242
Seattle Children's Hospital
Seattle, Washington, 98105
France3 sites
CHU Arnaud de Villeneuve
Montpellier, 34295
Hôpital Necker - Enfants Malades
Paris, 75015
Chu Hopital Des Enfants
Toulouse, 31059
Belarus2 sites
State Institution Republican Scientific And Practical Center For Pediatric Surgery
Minsk, 220013
Health Institution 4Th City Children'S Clinical Hospital
Minsk, 220118
China2 sites
Beijing Anzhen Hospital
Beijing, 100029
Shanghai Childrens Medical Center
Shanghai, 200127
Israel2 sites
Schneider Children's Medical Center
Petach Tikvah
Sheba Medical Center
Ramat Gan, 52621
Malaysia2 sites
Sarawak Heart Center
Kota Samarahan, 94300
Institut Jantung Negara (National Heart Institute)
Kuala Lumpur, 50400
Serbia2 sites
Univerzitetska Dečja Klinika
Belgrade, 11000
Institut Za Zdravstvenu Zastitu Majke I Deteta Srbije Dr Vukan Cupic
Belgrade, 11070
Taiwan2 sites
National Cheng Kung University Hospital
Tainan, 704
National Taiwan University Hospital
Taipei, 100
Germany1 site
Universitätsklinikum Freiburg Zentrum
Freiburg im Breisgau, 70106
Hungary1 site
Gottsegen Gyorgy Orszagos Kardiologiai Intezet, Felnott kardiologiai osztaly
Budapest, 1096
About this study
Official title: A Prospective, Multicenter, Open Label, Single Arm, Phase 2 Study to Investigate the Safety, Tolerability and Pharmacokinetics of Selexipag in Children With Pulmonary Arterial Hypertension
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.
Read the 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
- Being tested
- selexipag (Uptravi)
- Keywords
- Pediatric
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
selexipag (Uptravi)Drug
Also called ACT-293987, JNJ-67896049
Film-coated tablets for oral administration
| Study group | Role | What they receive |
|---|---|---|
| open label selexipag | Experimental | 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. Receives: Drug: selexipag (Uptravi) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-time Curve Over a Dose Interval at Steady State of Selexipag and Its Metabolite ACT-333679 Combined (AUCτ, ss, Combined)
AUCτ, ss, combined was defined as the area under the plasma concentration-time curve over one dosing interval at steady state. AUCτ,ss,combined was calculated as 1/38 AUCτ,ss,selexipag plus 37/38 AUCτ,ss,ACT-333679.
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Secondary outcomes (22)
Area Under the Plasma Concentration-time Curve Over a Dose Interval of Selexipag at Steady State (AUCτ,ss)
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Area Under the Plasma Concentration-Time Curve Over a Dose Interval of ACT-333679 at Steady State (AUCτ,ss)
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Maximum Observed Plasma Concentration of Selexipag at Steady State (Cmax,ss)
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Maximum Observed Plasma Concentration of ACT-333679 at Steady State (Cmax,ss)
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Time to Reach the Maximum Observed Plasma Concentration of Selexipag at Steady State (Tmax,ss)
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Time to Reach the Maximum Observed Plasma Concentration of ACT-333679 at Steady State (Tmax,ss)
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Trough Concentration of Selexipag at Steady State (Ctrough,ss)
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Trough Concentration of ACT-333679 at Steady State (Ctrough,ss)
Measured: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (End of Treatment [EOT] + 3 Days)
Measured: EOT+3 days (Up to Week 17)
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) (EOT + 3 Days)
Measured: EOT+3 days (Up to Week 17)
Number of Participants With Adverse Events (AEs) Leading to Permanent Discontinuation of Study Drug
Measured: Up to 7 years
Number of Participants With Treatment-emergent Deaths (EOT + 3 Days)
Measured: EOT+3 days (Up to Week 17)
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (EOT + 3 Days)
Measured: EOT+3 days (Up to Week 17)
Change From Baseline in Hematology Parameters (EOT + 3 Days)
Measured: EOT+3 days (Up to Week 17)
Change From Baseline in Chemistry Parameters (EOT + 3 Days)
Measured: EOT+3 days (Up to Week 17)
Number of Participants With Treatment-emergent Electrocardiogram (ECG) Abnormalities (EOT + 3 Days)
Measured: EOT+3 days (Up to Week 17)
Change From Baseline in Thyroid Stimulating Hormone (TSH) up to EOT + 3 Days
Measured: EOT+3 days (Up to Week 17)
Change From Baseline in Blood Pressure
Measured: Up to 7 years
Change From Baseline in Heart Rate
Measured: Up to 7 years
Change From Baseline Over Time in Height up to EOT+3 Days
Measured: EOT+3 days (Up to Week 17)
Change From Baseline Over Time in Body Mass Index (BMI) up to EOT + 3 Days
Measured: EOT+ 3 days (Up to Week 17)
Change From Baseline in Sexual Maturation (Tanner Stage) up to End of Treatment (EOT + 3 Days)
Measured: EOT+ 3 days (Up to Week 17)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2018
- Study start23 Jul 2018
- Primary completion28 Mar 2022
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Catherine Boisson, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03492177
- Sponsor's protocol ID
- AC-065A203
- Other IDs
- AC-065A203, 2022-503042-42-00
- Status last verified
- Sep 2026
- First submitted
- 3 Apr 2018
- Last updated
- 25 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Beghetti M, Axelsen LN, Borissoff JI, Farhan M, Grill S, Leng S, Russu A, Lesage C, Remenova T, Hsu Schmitz SF, Moledina S. A Prospective, Multicenter, Open-Label, Single-Arm Phase 2 Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Exploratory Efficacy of Selexipag in Children With Pulmonary Arterial Hypertension. Chest. 2026 May;169(5):1330-1344. doi: 10.1016/j.chest.2025.12.013. Epub 2025 Dec 20.
PubMed 41429287