Riociguat in Children With Pulmonary Arterial Hypertension (PAH)

Launched by BAYER · Sep 28, 2015

Keywords

ClinConnect Summary

This clinical trial is looking at a medication called riociguat to see how safe and effective it is for children aged 6 to less than 18 years who have pulmonary arterial hypertension (PAH), a serious condition that affects the blood vessels in their lungs and can make it hard to breathe. The trial will involve giving children different doses of riociguat over a period of up to 24 weeks, including both a phase where the dose may be adjusted and a phase where the dose remains stable. The goal is to gather information on how well the medication works and how children tolerate it.

To participate in the trial, children must have a confirmed diagnosis of PAH and be receiving standard treatments for at least 12 weeks before joining. This includes conditions like idiopathic PAH (where the cause is unknown) or PAH related to other health issues, like heart defects. However, children with certain health problems or those taking specific medications cannot join the study. Parents and guardians will need to give consent for their children to participate, and girls who are able to become pregnant will need to agree to use effective birth control during the study. Overall, this trial aims to help improve treatment options for children with this challenging condition.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Children from 6 years to less than 18 years of age with pulmonary arterial hypertension (PAH)
• * Diagnosed with PAH :
• • Idiopathic (IPAH)
• • Hereditable (HPAH)
• • PAH associated with (APAH)
• • Connective tissue disease
• • Congenital heart disease with shunt closure more than 6 months ago (no open shunts, confirmed by RHC no less than 4 months after surgery)
• Regardless of the type of PAH, the following findings are not exclusionary:
• • --- Patent foramen ovale (PFO) and asymptomatic, isolated, ostium secundum atrial septal defect (OS-ASD) ≤ 1 cm (both confirmed by echocardiogram) and not associated with hemodynamic alterations indicative of significant shunt, e.g. Qp/Qs ratio less \<1.5:1 are not exclusionary
• • PAH diagnosed by right heart catheterization (RHC) at any time prior to enrolment (for patients with closed shunts - RHC no less than 4 months after surgery)
• • PAH confirmed by a RHC at any time prior to start of study, with mean pulmonary artery pressure (PAPmean) ≥25 mmHg at rest, pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) ≤15 mmHg, and pulmonary vascular resistance (PVR) \>240 dyn•sec•cm\^-5 (i.e., ≥3.0 wood units•m\^2)
• • Patients must be on standard of care PAH medications, allowing Endothelin Receptor Antagonists (ERA) and/or Prostacyclin Analogues (PCA), for at least 12 weeks prior to baseline visit.
• Two groups of patients will be included:
• • Prevalent: Patients currently on PAH medication (allowing ERA and/or PCA) who need additional treatment (discretion of the investigator)
• • Incident: Treatment naïve patients initiated on PAH medication (allowing ERA and /or PCA) and then riociguat added once patients are stable on standard of care
• • WHO functional class I-III
• • Adolescent females of childbearing potential can only be included in the study if a pregnancy test is negative. Adolescent females of childbearing potential must agree to receive sexual counseling and use effective contraception as applicable. 'Effective contraception' is defined as progestogen-only hormonal contraception associated with inhibition of ovulation (implant), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), or any combination of adequate methods of birth control (e.g. condoms with hormonal contraception). Agreement to use contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration.
• • Young men must agree to use adequate contraception when sexually active.
• • Written inform consent provided and if applicable child assent provided
• Exclusion Criteria:
• • Concomitant use of the following medications: phosphodiesterase (PDE) 5 inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific phosphodiesterase (PDE) inhibitors (theophylline, dipyridamole), nitrates or NO donors (such as amyl nitrite) in any form
• • -- Pretreatment with NO donors (e.g. nitrates) within the last 2-weeks before visit 1. The use of any drug including NO acutely for testing during catheterization is not an exclusion criterion.
• • Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization or any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening
• • Systolic blood pressure (SBP) more than 5 mmHg lower than the age-, sex- and height-adapted level of the 50th SBP percentile (NHBPEP, 2004)
• • History of left-sided heart disease, including valvular disease or heart failure
• • Pulmonary hypertension related to conditions other than specified in the inclusion criteria
• • WHO functional class IV
• • Pulmonary veno-occlusive disease
• • Screening aspartate transaminase (AST) and/ or alanine transaminase (ALT) more than 3 times the upper limit of normal (ULN)
• • Severe restrictive lung disease
• • Severe congenital abnormalities of the lung, thorax, and diaphragm
• • Clinically relevant hepatic dysfunction (especially Child Pugh C)
• • Renal insufficiency (estimated glomerular filtration rate \<30 mL/min/1.73m\^2 e.g. calculated based on Schwartz formula)
• • PH associated with idiopathic interstitial pneumonia (PH-IIP)