Riociguat for treatment of PAH in children from 6 to less than 18 years old

Phase 1

• Conditions: Pulmonary arterial hypertension (PAH); MedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2014-003952-29-PL
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-04-13
• Last Update Posted: 28 August 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Children aged =6 to <18 years
2. Diagnosed with PAH :
- Idiopathic (IPAH)
- Hereditable (HPAH)
- PAH associated with (APAH)
o Connective tissue disease
o 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:
o Patent foramen ovale (PFO)
o 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
3. Diagnosis of PAH confirmed by right heart catheterization (RHC) at any time prior to enrolment (for patients with closed shunts – RHC no less than 4 months after surgery)
4. Pulmonary arterial hypertension 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•m2)
5. 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:
o Prevalent: Patients currently on PAH medication (allowing ERA and/or PCA)
who need additional treatment (discretion of the investigator)
o 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
6. WHO functional class I-III
7. 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.
8. Young men must agree to use adequate contraception when sexually active.
9. Written inform consent provided and if applicable child assent provided
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.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
(Footnote: Pretreatment with the phosphodiesterase (PDE) 5 inhibitor Sildenafil is allowed up to 24 h prior to start of riociguat treatment (Visit 1). Pretreatment with the phosphodiesterase (PDE) 5 inhibitor tadalafil is allowed up to 3 days prior to start of riociguat treatment (Visit 1). Patients are not expected to be withdrawn from treatment with PDE5i for the purpose of entering into this trial. During the period without PDE5i, patients who received treatment with PDE5i are expected to be on stable clinical condition and receiving standard of care treatment with ERA and/or PCAs.)
2. 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.
3. 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
4. Systolic blood pressure (SBP) more than 5 mmHg lower than the age-, sex- and height-adapted level of the 50th SBP percentile (NHBPEP, 2004)
5. History of left-sided heart disease, including valvular disease or heart failure
6. Pulmonary hypertension related to conditions other than specified in the inclusion criteria
7. WHO functional class IV
8. Pulmonary veno-occlusive disease
9. Screening aspartate transaminase (AST) and/ or alanine transaminase (ALT) more than 3 times the upper limit of normal (ULN)
10. Non-stable disease status, e.g. , signs and symptoms of decompensated right heart failure
11. Severe bronchial asthma
12. Severe restrictive lung disease
13. Severe congenital abnormalities of the lung, thorax, and diaphragm
14. Clinically relevant hepatic dysfunction (especially Child Pugh C)
15. Renal insufficiency (estimated glomerular filtration rate <30 mL/min/1.73m2 e.g. calculated based on Schwartz formula)
16. Subject with hypersensitivity to the investigational drug or any of the excipients
17. Active smoking of tobacco of any type or quantity. Smoking marijuana is also not permitted.
18. Subjects with any other condition that is not recommended with riociguat
19. Previous assignment to treatment during this study
20. Previous (within 30 days) or concomitant participation in another clinical study with investigational medicinal product(s)
21. Any condition that, according to treating physician, might jeopardize subject's participation and compliance with procedures indicated in this protocol.
22. PH associated with idiopathic interstitial pneumonia (PH-IIP)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified