Investigational Trial to Evaluate Safety and Tolerability of Treprostinil in Children Diagnosed With PAH

Pulmonary Arterial Hypertension Clinical Trial

Official title:

Open-label, Single-arm, Non-controlled Trial to Evaluate Safety and Tolerability of Treprostinil Sodium in Children Below the Age of 18 Years Diagnosed With Pulmonary Arterial Hypertension (PAH)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06350032
• Other study ID #: TREPaed
• Secondary ID: 2023-505082-91-0
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 2024
• Est. completion date: November 2028

Study information

• Verified date: April 2024
• Source: AOP Orphan Pharmaceuticals AG
• Contact: Clinical Project Manager
• Phone: 4366488375206
• Email: trepaed[@]aop-health.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to evaluate safety and tolerability of preservative-free parenteral treprostinil in paediatric patients with PAH (PH Group 1) who are below 18 years of age. The main question it aims to answer is:

• if preservative-free parenteral treprostinil is safe and tolerable in the treatment of paediatric PAH in patients who are either treatment-naïve or have been previously treated with commercially available parenteral treprostinil formulations.

Participants will receive either subcutaneous (SC) or intravenous (IV) preservative-free treprostinil and will be observed for 5 months (20 weeks ± 1 week).

Description:

In this study, a preservative-free treprostinil solution provided in a single-use vial will be used. Efficacy of treprostinil for the treatment of PAH in pulmonary hypertension (PH) Group 1 in children is reported throughout literature. However, since the removal of the preservative might impact the safe use of the parenteral solution for infusion, the safety profile of the newly developed preservative-free treprostinil solution will be assessed within this trial.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: November 2028
• Est. primary completion date: November 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent by the parents or the legal representatives and written assent from appropriately aged participants

2. Males or females from birth to under 18 years of age at the time informed consent was signed

3. Confirmed diagnosis of severe PAH classified as PH Group 1 requiring a treatment with prostacyclin infusion

4. Current diagnosis of PAH confirmed by right heart catheterisation (RHC) at screening or by historical RHC prior to screening with following haemodynamic findings:

• Mean pulmonary arterial pressure (mPAP) >20 mmHg

• Pulmonary vascular resistance Index (PVRI) >3 Wood Units (WU) m² If RHC is not possible due to medical reasons (e.g. neonates and infants), the confirmation by ECHO at the screening is sufficient.

5. Prostacyclin naïve or patients pre-treated with SC or IV treprostinil prior to screening

6. A subject is eligible to participate in this study, as assessed by the investigator, if they are of:

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or,

• Child-bearing potential - has a negative pregnancy test and is not lactating and, if sexually active, agrees to continue to use 2 reliable methods of contraception until study completion and for at least 30 days following the last dose of study drug. Examples of reliable birth control methods include true abstinence as a lifestyle choice (periodic sexual abstinence method is not acceptable); the use of oral contraceptives; a reliable barrier method of birth control (diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices)

Exclusion Criteria:

1. Known intolerance to prostacyclin analogues

2. PH related to conditions other than specified above

3. Unrepaired congenital heart disease if surgery is planned within next 5 months

4. Subjects diagnosed with any lung disease

5. Acutely decompensated heart failure within previous 30 days from screening

6. Subjects who have had an atrial septostomy or potts shunt within the previous 6 months of screening

7. Any clinically significant laboratory abnormality that precludes initiation or continuation of treprostinil therapy

8. Moderate to severe hepatic dysfunction as defined by elevated liver function tests (aspartate aminotransferase or alanine aminotransferase) =3 times the upper limit of normal at Screening, or Child Pugh class B or C hepatic disease

9. Subjects who are pregnant or breastfeeding

10. Haematological abnormalities (e.g., severe anaemia, Hgb <10 g/dL, leukopenia, White Blood Cells (WBC) <2500/µL)

11. History of substance use disorder, unless a proof of abstinence =1 year is provided

12. Other concurrent severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study

13. Participation in another clinical trial of an investigational drug or device (including with placebo) within 30 days or 5 half-lives prior to screening, which-ever is longer

14. Patients not able to handle pumps and infusion site if there is no parent, family member, guardian present in their household taking over pump handling or if they are not treated in hospital set-up

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• preservative-free parenteral treprostinil
Continuous infusion of either SC or IV preservative-free treprostinil. The dosing is not stipulated by the study protocol and will be done according to patient needs.

Locations

Country	Name	City	State
Austria	Medizinische Universität Wien	Vienna
France	Necker-Enfants Malades Hospital, Paris	Paris
Hungary	Gottsegen National Cardiovascular Center	Budapest
Spain	Ramón y Cajal University Hospital	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
AOP Orphan Pharmaceuticals AG

Countries where clinical trial is conducted

Austria,  France,  Hungary,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in quality of Life (QoL)	Change from baseline in quality of Life (QoL) as assessed by the Pediatric Quality of Life Inventory (PedsQoL Version 4.0) questionnaire.; Rating from 0 (never) to 4 (almost always) per question. Questionnaire will be completed by pediatric patient (version appropriate for age group) and parents/caregivers.	5 months (20 weeks ± 1 weeks)
Other	Change from baseline in 6-minute walk distance (6MWD)	Change from baseline in 6MWD (patients > 6 years)	5 months (20 weeks ± 1 weeks)
Other	Change from baseline in World Health Organization Functional Class (WHO FC)	Change in WHO FC class assessment based on current PH guidelines ranging from class I to class IV, whereas class IV means severe limitations.	5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - RA/RV enlargement	right atrium (RA) / right ventricle (RV)	5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - RV systolic dysfunction		5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - RV/LV end-systolic ratio (PSAX)	RV / left ventricle (LV)	5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - tricuspid annular plane systolic excursion (TAPSE)		5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - S/D ratio (TR jet)		5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - Pulmonary Artery Acceleration Time (PAAT)		5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - pericardial effusion		5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - eccentricity index		5 months (20 weeks ± 1 weeks)
Other	Change from baseline in echocardiography (ECHO) parameters - acceleration time		5 months (20 weeks ± 1 weeks)
Other	Change from baseline in plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels		5 months (20 weeks ± 1 weeks)
Other	Treprostinil plasma concentration	For treprostinil plasma concentration analysis one 0,5 ml blood sample for patients = 20 kg and one 1ml blood (K3-EDTA) sample for patients > 20kg will be taken.	5 months (20 weeks ± 1 weeks)
Primary	Frequency and seriousness of adverse events and adverse drug reactions	The frequency and seriousness of adverse events and adverse drug reactions during the first 5 months (20 weeks ± 1 weeks) of treatment according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).	5 months (20 weeks ± 1 weeks)