Open-label, single-arm, non-controlled trial to evaluate the safety and tolerability of treprostinil sodium in children below the age of 18 years with pulmonary arterial hypertension (PAH)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aop Orphan Pharmaceuticals GmbH

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

29 May 2024 → ongoing

Decision date (initial)

2024-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AOP Orphan Pharmaceuticals GmbH

External identifiers

EU CT number

2023-505082-91-00

WHO UTN

U1111-1297-2710

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the safety and tolerability of preservative-free treprostinil in paediatric patients with PAH (PH Group 1) who are below 18 years of age and are either treatment naive or have been previously treated with commercially available parenteral treprostinil formulatio

Secondary objectives 1

1. To assess the efficacy of preservative-free treprostinil in terms of quality of life, symptom improvement, and risk assessment.

Conditions and MedDRA coding

Pulmonary Arterial Hypertension (PAH)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003182-PIP01-22

Plan to share IPD

No

IPD plan description

Individual participant data (IPD) from this study will not be shared. The data will remain confidential in accordance with applicable data protection regulations and ethical guidelines.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Signed informed consent by the parents or the legal representatives and written assent from appropriately aged participants
2. 2. Males or females from birth to under 18 years of age at the time informed consent was signed
3. 3. Confirmed diagnosis of severe PAH classified as PH Group 1 requiring a treatment with prostacyclin infusion
4. 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. 5. PAH-treatment naïve or pretreated patients
6. 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 15

1. 1. Known intolerance to prostacyclin analogues
2. 6. Acutely decompensated heart failure within previous 30 days from screening
3. 7. Subjects who have had an atrial septostomy or potts shunt within the previous 6 months of screening
4. 8. Any clinically significant laboratory abnormality that precludes initiation or continuation of treprostinil therapy
5. 9. 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
6. 15. 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
7. 10. Subjects who are pregnant or breastfeeding
8. 11. Haematological abnormalities (e.g., severe anaemia, Hgb <10 g/dL, leukopenia, WBC <2500/µL)
9. 12. History of substance use disorder, unless a proof of abstinence ≥1 year is provided
10. 13. 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
11. 14. Participation in another clinical trial of an investigational drug or device (including placebo) within 5 half-lives (max. 30 days) prior to screening
12. 3. PH related to conditions other than specified above
13. 4. Unrepaired congenital heart disease if surgery is planned within next 5 months
14. 5. Subjects diagnosed with any lung disease
15. 2. Patient receiving any other prostacyclin analogue, except parenteral treprostinil, or any prostacyclin receptor agonist within 72 hours prior to enrolment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 7

1. Change from baseline in quality of Life (QoL) as assessed by the Pediatric Quality of Life Inventory (PedsQoL Version 4.0) questionnaire.
2. Change from baseline in 6MWD (patients > 6 years)
3. Change from baseline in WHO FC
4. Change from baseline in echocardiography (ECHO) parameters
5. Change from baseline in plasma N-terminal pro-brain natriuretic peptide (NTproBNP)
6. The frequency and seriousness of adverse events and adverse drug reactions according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) during the observational period
7. Treprostinil plasma concentration

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aop Orphan Pharmaceuticals GmbH

Sponsor organisation

Aop Orphan Pharmaceuticals GmbH

Address

Leopold-Ungar-Platz 2, Döbling Döbling

City

Vienna

Postcode

1190

Country

Austria

Scientific contact point

Organisation

Aop Orphan Pharmaceuticals GmbH

Contact name

AOP Orphan Pharmaceuticals GmbH

Public contact point

Organisation

Aop Orphan Pharmaceuticals GmbH

Contact name

AOP Orphan Pharmaceuticals GmbH

Third parties 5

Locations

6 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 79 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications