An extension study to evaluate the long-term efficacy and safety of odevixibat (A4250) in children with biliary atresia (BOLD-EXT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ipsen Pharma

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

14 Dec 2022 → ongoing

Decision date (initial)

2023-01-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ipsen Pharma

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate a sustained effect of odevixibat on native liver survival (NLS) in children with biliary atresia (BA) who have completed study A4250-011 (BOLD)

Secondary objectives 1

1. • To demonstrate a sustained effect of odevixibat on serum bile acids and prevention of liver fibrosis in children with BA • To evaluate the effect of odevixibat on lowering serum bile acids in patients who previously received placebo in Study A4250-011 • To evaluate the long-term safety and tolerability of repeated daily doses of odevixibat • To evaluate the effect of odevixibat on growth • To evaluate the effect of odevixibat on sentinel events (defined as clinically significant ascites, bleeding gastroesophageal varices, thrombocytopenia [platelet count <150,000/μL], liver transplant, or death)

Conditions and MedDRA coding

Biliary Atresia

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board. Supporting Information Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later. Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available at https://vivli.org/members/ourmembers/.”

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Completion of the 104-week Treatment Period of Study A4250-011 22. Signed informed consent by the patient’s parent(s) or legal guardian

Exclusion criteria 1

1. 1. Patients who were not compliant with study drug treatment or procedures in Study A4250-011 as per the investigator’s discretion 2. Any conditions or abnormalities which, in the opinion of the investigator, may compromise the safety of the patient, or interfere with the patient participating in or completing the study 3. Known hypersensitivity to any components of odevixibat 4. Patients who are scheduled for a liver transplant or are likely to require a liver transplant in the immediate future based on the investigator’s judgment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time from the date of first dose of study treatment to first occurrence of liver transplant, or death

Secondary endpoints 5

1. • Change in aspartate aminotransferase (AST) to platelet ratio index (APRI) score from baseline to Weeks 4, 13, 26, 39, 52, 78, and 104 • Change in fibrosis-4 (Fib-4) score from baseline to Weeks 4, 13, 26, 39, 52, 78 and 104 • Change from baseline in serum bile acids at Weeks 26, 52, 78, and 104
2. • Change in growth from baseline to Weeks 26, 52, 78, and 104 after initiation of odevixibat treatment, defined as the linear growth deficit (height for age, weight for age, and body mass index [BMI]) compared to a standard growth curve (Z-score, standard deviation [SD] from P50); mid-arm circumference
3. • Time to onset of first sentinel event during the 104-week treatment period.
4. • Change in pediatric end-stage liver disease (PELD) score from baseline to Weeks 26, 52, 78, and 104
5. • Proportion of patients who are alive and have not undergone a liver transplant at Weeks 26, 52, 78 and 104

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ipsen Pharma

Sponsor organisation

Ipsen Pharma

Address

70 Rue Balard

City

Paris

Postcode

75015

Country

France

Scientific contact point

Organisation

Ipsen Pharma

Contact name

Clinical Operations Department

Public contact point

Organisation

Ipsen Pharma

Contact name

Clinical Operations Department

Third parties 7

Locations

8 EU/EEA countries · 17 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 207 files

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

Application history

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