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A Study of Selexipag as Add-On Treatment to Standard of Care in Children With Pulmonary Arterial Hypertension (SALTO)

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ClinicalTrials.gov Identifier: NCT04175600
Recruitment Status : Recruiting
First Posted : November 25, 2019
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE November 8, 2019
First Posted Date  ICMJE November 25, 2019
Last Update Posted Date April 14, 2021
Actual Study Start Date  ICMJE January 16, 2020
Estimated Primary Completion Date December 9, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2019)
Time to Disease Progression [ Time Frame: From randomization up to 7 days after study treatment discontinuation (up to 5 years) ]
Time to disease progression is the time from randomization up to 7 days after study treatment discontinuation. Disease progression is defined as the first occurrence of either of the following components: Death (all causes), Atrial septostomy or Potts' anastomosis, or registration on lung transplant list, Hospitalization due to worsening pulmonary arterial hypertension (PAH), Clinical worsening of PAH.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
  • Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious AEs [ Time Frame: Up to 5 years ]
    An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are AEs with onset during the intervention period or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
  • Percentage of Participants with AEs Leading to Premature Discontinuation of Study Treatment [ Time Frame: Up to 5 years ]
    Percentage of participants with AEs leading to premature discontinuation of study treatment will be reported.
  • Change from Baseline in Systolic and Diastolic Arterial Blood Pressure [ Time Frame: Baseline up to end of treatment (EOT) (up to 8.3 years) ]
    Change from baseline in systolic and diastolic arterial blood pressure to all assessed time points will be reported.
  • Change from Baseline in Pulse Rate [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Change from baseline in pulse rate to all assessed time points will be reported.
  • Change from Baseline in Body Weight [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Change from baseline in body weight to all assessed time points will be reported.
  • Change from Baseline in Height [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Change from baseline in height to all assessed time points will be reported.
  • Sexual Maturation (Tanner Stage) Change from Baseline to all Assessed Time Points [ Time Frame: Up to 3 days after study treatment discontinuation (up to EOT) (multiple timepoints up to 8.3 years) ]
    The sexual maturation change as per Tanner stage will be assessed from baseline to all assessed time points. Tanner stage I is defined as no pubic hair at all (prepubertal Dominic state); stage II is defined as a small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females); stage III is defined as when the hair becomes more coarse and curly, and begins to extend laterally; stage IV is defined as adult-like hair quality, extending across pubis but sparing medial thighs; and stage V is defined as when the: hair extends to medial surface of the thighs.
  • Percentage of Participants with Treatment-emergent Electrocardiogram Abnormalities [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Percentage of participants with treatment-emergent electrocardiogram abnormalities will be reported.
  • Percentage of Participants with Treatment-emergent Marked Laboratory Abnormalities [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Percentage of participants with treatment-emergent marked laboratory (serum chemistry [including pregnancy testing and thyroid markers] and hematology) abnormalities will be reported.
  • Treatment-emergent Change from Baseline in Thyroid Stimulating Hormone [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Treatment-emergent change from baseline in thyroid stimulating hormone over time will be reported.
  • Time to First Clinical Event Committee (CEC)-confirmed Hospitalization and Death for PAH [ Time Frame: Until 7 days after study treatment discontinuation (Up to 8.3 years) ]
    Time to first CEC-confirmed hospitalization and death for PAH is the time (days) from randomization to first occurrence of CEC-confirmed hospitalization for PAH or death due to PAH up to 7 days after study intervention discontinuation.
  • Trough Plasma Concentration at Steady-state (Ctrough,ss) of Selexipag and its Metabolite ACT-333679 [ Time Frame: Weeks 16, 24 and every 12 weeks thereafter (up to 8.3 years) ]
    Ctrough,ss is defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the pharmacokinetic sampling and will be reported for Selexipag and its metabolite ACT-333679.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2019)
  • Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious AEs [ Time Frame: Up to 5 years ]
    An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are AEs with onset during the intervention period or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
  • Percentage of Participants with AEs Leading to Premature Discontinuation of Study Treatment [ Time Frame: Up to 5 years ]
    Percentage of participants with AEs leading to premature discontinuation of study treatment will be reported.
  • Treatment-emergent Change from Baseline in Systolic and Diastolic Arterial Blood Pressure [ Time Frame: Baseline up to end of treatment (EOT) (up to 8.3 years) ]
    Treatment-emergent change from baseline in systolic and diastolic arterial blood pressure to all assessed time points will be reported.
  • Treatment-emergent Change from Baseline in Pulse Rate [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Treatment-emergent change from baseline in pulse rate to all assessed time points will be reported.
  • Treatment-emergent Change from Baseline in Body Weight [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Treatment-emergent change from baseline in body weight to all assessed time points will be reported.
  • Treatment-emergent Change from Baseline in Height [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Treatment-emergent change from baseline in height to all assessed time points will be reported.
  • Sexual Maturation (Tanner Stage) from Baseline to all Assessed Time Points [ Time Frame: Up to 3 days after study treatment discontinuation (up to EOT) (multiple timepoints up to 8.3 years) ]
    The sexual maturation as per Tanner stage will be assessed from baseline to all assessed time points. Tanner stage I is defined as no pubic hair at all (prepubertal Dominic state); stage II is defined as a small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females); stage III is defined as when the hair becomes more coarse and curly, and begins to extend laterally; stage IV is defined as adult-like hair quality, extending across pubis but sparing medial thighs; and stage V is defined as when the: hair extends to medial surface of the thighs.
  • Percentage of Participants with Treatment-emergent Electrocardiogram Abnormalities [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Percentage of participants with treatment-emergent electrocardiogram abnormalities will be reported.
  • Percentage of Participants with Treatment-emergent Marked Laboratory Abnormalities [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Percentage of participants with treatment-emergent marked laboratory (serum chemistry [including pregnancy testing and thyroid markers] and hematology) abnormalities will be reported.
  • Treatment-emergent Change from Baseline in Thyroid Stimulating Hormone [ Time Frame: Baseline up to EOT (up to 8.3 years) ]
    Treatment-emergent change from baseline in thyroid stimulating hormone over time will be reported.
  • Time to First Clinical Event Committee (CEC)-confirmed Hospitalization and Death for PAH [ Time Frame: Until 7 days after study treatment discontinuation (Up to 8.3 years) ]
    Time to first CEC-confirmed hospitalization and death for PAH is the time (days) from randomization to first occurrence of CEC-confirmed hospitalization for PAH or death due to PAH up to 7 days after study intervention discontinuation.
  • Trough Plasma Concentration at Steady-state (Ctrough,ss) of Selexipag and its Metabolite ACT-333679 [ Time Frame: Weeks 16, 24 and every 12 weeks thereafter (up to 8.3 years) ]
    Ctrough,ss is defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the pharmacokinetic sampling and will be reported for Selexipag and its metabolite ACT-333679.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Selexipag as Add-On Treatment to Standard of Care in Children With Pulmonary Arterial Hypertension
Official Title  ICMJE A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group, Event-Driven, Group-Sequential Study With Open-Label Extension Period to Assess the Efficacy and Safety of Selexipag as Add-On Treatment to Standard of Care in Children Aged >=2 to <18 Years With Pulmonary Arterial Hypertension
Brief Summary 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.
Detailed Description Pediatric PAH is a rare and progressive disorder associated with considerable morbidity and mortality. Given the significant medical need to develop treatments in children with PAH, further clinical studies in the pediatric population are therefore needed to provide more data for the management of PAH in children. Selexipag (JNJ-67896049) is an orally available, selective, and long-acting non-prostanoid agonist of the prostacyclin receptor approved and commercially available for the treatment of adult participants with PAH. Selexipag and its metabolite possess anti-fibrotic, anti-proliferative, and anti-thrombotic properties. Currently, no medicines targeting prostacyclin pathway are approved for pediatric use in PAH. An effective and orally available therapy acting on the prostacyclin receptor such as selexipag introduced at medically appropriate stage of PAH disease, and primarily in combination with current first-line oral PAH-specific medicines in participants in need of additional therapy because of insufficient disease control would represents a major advance to the therapeutic management of PAH pediatric participants. This study consists of a screening period of up to 6 weeks and a double-blind treatment period, including up-titration and maintenance periods, followed by a 3-year open-label extension period (OLEP) and a 30-day safety follow-up period that occurs after the last dose of study intervention (either double-blind or open-label). Safety, pharmacokinetic and efficacy assessments will be performed during the study. An Independent Data Monitoring Committee (IDMC) will be established to monitor data on an ongoing basis, to review interim data, and to ensure the continuing safety of the participants enrolled in this study. The approximate duration of the study is 8.3 years.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hypertension, Pulmonary
Intervention  ICMJE
  • Drug: Selexipag
    Selexipag tablet will be administered orally.
    Other Name: JNJ-67896049
  • Drug: Placebo
    Matching placebo tablets will be administered orally.
Study Arms  ICMJE
  • Experimental: Selexipag
    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.
    Intervention: Drug: Selexipag
  • Placebo Comparator: Placebo
    Participants will receive matching placebo based on the body weight on Day 1 and will continue thereafter with twice daily dosing.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 21, 2019)
237
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 10, 2028
Estimated Primary Completion Date December 9, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants between greater than or equal to (>=) 2 and less than (<) 18 years of age weighing >=9 kilogram (kg) at randomization
  • Pulmonary arterial hypertension (PAH) diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before participant's screening
  • PAH (World Health Organization [WHO] Group 1), including participants with Down syndrome, of the following etiologies: Idiopathic PAH (IPAH); Heritable PAH (HPAH); PAH associated with congenital heart disease (PAH-associated with congenital heart disease [aCHD]) (PAH with coincidental CHD [that is, a small atrial septal defect, ventricular septal defect, or patent ductus arteriosus that does not itself account for the development of elevated PVR] and if approved by the BCAC) and Post-operative PAH (persisting / recurring/ developing >=6 months after repair of CHD); Drug or toxin-induced; PAH associated with Human immunodeficiency virus (HIV)
  • WHO functional class (FC) II and III
  • Participants treated with at least 1 PAH-specific treatment, example, an Endothelin receptor antagonist (ERA) and/or a Phosphodiesterase type-5 (PDE-5) inhibitor/soluble guanylate cyclase stimulator, provided that the treatment dose(s) has been stable for at least 3 months prior to screening

Exclusion Criteria:

  • PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis
  • PAH associated with Eisenmenger syndrome
  • Previous exposure to Uptravi (selexipag)
  • Known concomitant life-threatening disease with a life expectancy <12 months
  • Pregnant, planning to become pregnant, or lactating
  • Known allergies, hypersensitivity, or intolerance to selexipag or its excipients
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Australia,   Belarus,   Belgium,   Brazil,   Bulgaria,   Canada,   China,   Colombia,   Denmark,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Korea, Republic of,   Lithuania,   Malaysia,   Mexico,   Poland,   Portugal,   Russian Federation,   Serbia,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   Ukraine,   United States,   Vietnam
Removed Location Countries Argentina,   Austria,   Romania
 
Administrative Information
NCT Number  ICMJE NCT04175600
Other Study ID Numbers  ICMJE CR108716
2019-002817-21 ( EudraCT Number )
AC-065A310 ( Other Identifier: Actelion )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency
Responsible Party Actelion
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Actelion Clinical Trial Actelion
PRS Account Actelion
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP