A clinical study to confirm the doses of selexipag to be used in children with pulmonary arterial hypertension

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Actelion Pharmaceuticals Ltd.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

23 Jul 2018 → ongoing

Decision date (initial)

2023-08-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and Johnson

External identifiers

EU CT number

2022-503042-42-00

EudraCT number

2018-000145-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Safety

The primary objective of the study is to confirm the selexipag starting dose(s), selected based on pharmacokinetic (PK) extrapolation from adults, that leads to similar exposures as adult doses in children from ≥ 2 to < 18 years of age, with pulmonary arterial hypertension (PAH), by investigating the PK of selexipag and its active metabolite ACT-333679 in this population

Conditions and MedDRA coding

Pulmonary Arterial Hypertension

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000997-PIP01-10

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparecy. 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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Signed and dated informed consent by the parent(s) or Legally authorized representative(s) AND assent from developmentally capable children
2. 2. Males or females between ≥ 2 and < 18 years of age at Baseline / Enrollment / Visit 2 weighing ≥ 9 kg
3. 3. PAH diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before the participants's enrollment
4. 4. PAH with one of the following etiologies: • idiopathic (iPAH), • heritable (hPAH), • associated with congenital heart disease (CHD): – PAH with co-incidental CHD – Post-operative PAH (persisting/ recurring/ developing ≥ 6 months after repair of CHD) Drug or toxin-induced PAH • PAH associated with HIV • PAH associated with connective tissue disease
5. 5. Word Health Organizaition functional class (WHO FC) II to III
6. 6. Participants treated with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, provided that the treatment dose(s) has been stable for at least 3 months prior to enrollment, or participants who are not candidates for these therapies
7. 7. Females of childbearing potential must have a negative pregnancy test at Screening and at Enrollment, and must agree to undertake monthly pregnancy tests, and to use a reliable method of contraception (if sexually active) from screening up to study drug discontinuation + 30 days (EOS)

Exclusion criteria 30

1. 1. Participants with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis
2. 4. Participants with cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, univentricular heart, or pulmonary atresia with ventricular septal defect, as well as subjects with Fontan palliation
3. 5. Participants with PH due to lung disease and/or hypoxia. For subjects with Down syndrome, exclusion of lung disease and hypoxia causing PH should be documented (e.g., computed tomography scan, polysomnography, lung function tests)
4. 6. Previous treatment with Uptravi® (selexipag) within 2 weeks prior to enrollment
5. 7. Previous having received prostacyclin (epoprostenol) or prostacyclin analogs2 (i.e., treprostinil, iloprost, beraprost) within 2 months prior to enrollment or who are scheduled to receive any of these compounds during the trial
6. 8. Treatment with another investigational drug within 4 weeks prior to enrollment
7. 9. Treatment with strong and moderate inhibitors of CYP2C8 (eg, gemfibrozil, clopidogrel, deferasirox, teriflunomide) within 2 weeks prior to enrollment until the last dose of selexipag + 3 days
8. 16. 1 Moderate or severe hepatic impairment, eg, Child-Pugh Class B or C [see Appendix 4]
9. 17. Clinical signs of hypotension that, in the investigator's judgment, would preclude the initiation of a PAH-specific therapy
10. 18. Participants with severe renal insufficiency (estimated creatinine clearance < 30 mL/min or serum creatinine > 221 μmol/L)
11. 19. Severe coronary heart disease or unstable angina as assessed by the investigator
12. 10. Treatment with inhibitors of UGT1A3 and UGT2B7 (valproic acid, probenecid, and fluconazole) are prohibited from 2 weeks prior to enrollment and until the last dose of selexipag + 3 days
13. 20. Myocardial infarction within the last 6 months prior to enrollment
14. 21. Decompensated cardiac failure if not under close supervision
15. 22. Severe arrhythmias as assessed by the investigator
16. 23. Cerebrovascular events (eg, transient ischemic attack, stroke) within the last 3 months prior to enrollment.
17. 24. Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to PH
18. 25. Pregnancy (including family planning) or breastfeeding
19. 26. Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations
20. 27. Drug or substance abuse, or any condition that, in the opinion of the investigator, may prevent compliance with the protocol or adherence to study treatment
21. 28. Loss of 250 mL or more of blood within 3 months prior to screening
22. 29. History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism, or excretion of the study treatment(s) (e.g., cholecystectomy)
23. 11. Any PAH-related surgical intervention planned, or participants listed for organ transplantation related to PAH
24. 12. History or current suspicion of intussusception or ileus or gastrointestinal obstruction, per investigator's judgment
25. 13. Known concomitant life-threatening disease with a life expectancy < 12 months
26. 14. Uncontrolled thyroid disease, per investigator's judgment
27. 15. Hemoglobin or hematocrit < 75% of the lower limit of normal range
28. 2. Participants with PAH associated with Eisenmenger syndrome
29. 3. Participants with moderate to large left-to-right shunts
30. 30. "Criterion deleted per Amendment 6".

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary pharmacokinetic (PK) endpoint: - Model-based exposure (AUCτ,ss, combined) of selexipag and ACT- 333679 corrected for their potency, determined during the 12 weeks up- titration period

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Actelion Pharmaceuticals Ltd.

Sponsor organisation

Actelion Pharmaceuticals Ltd.

Address

Gewerbestrasse 16

City

Allschwil

Postcode

4123

Country

Switzerland

Scientific contact point

Organisation

Actelion Pharmaceuticals Ltd.

Contact name

CTIS Point of Contact

Public contact point

Organisation

Actelion Pharmaceuticals Ltd.

Contact name

CTIS Point of Contact

Third parties 4

Locations

3 EU/EEA countries · 4 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 28 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