This study has been transitioned to CTIS with ID 2023-509028-17-00 check the CTIS register for the current data. To demonstrate a sustained effect of odevixibat on pruritus in patients with ALGS who have completed study A4250-012 (ASSERT)
ID
Source
Brief title
Condition
- Hepatobiliary disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline in scratching through Week 72 as measured by the Albireo
observer-reported outcomes (ObsRO) caregiver instrument
Secondary outcome
• Change in serum bile acid levels from baseline to Week 72
• Change from baseline through Week 72 in patient reported and observer
reported itching and scratching severity scores, respectively, for the morning
and evening assessments
• Percentage of patients achieving a clinically meaningful decrease in pruritus
(pruritus responders) at each visit as measured by the Albireo ObsRO/patient
reported outcomes (PRO) instruments
• Change from baseline to Week 72 in sleep parameters as measured with the
Albireo ObsRO/PRO instruments (e.g. tiredness and number of awakenings)
• Change from baseline to Week 72 in Pediatric Quality of Life Inventory
(PedsQL) scores
• Assessment of Global Symptom Relief from baseline to Weeks 4, 12, 24, 48 and
72 as measured by patient, caregiver, and clinician Global Impression of
Symptoms (PGIS, CaGIS, CGIS) items
• Assessment of Global Symptom Relief as measured by patient, caregiver, and
clinician Global Impression of Change (PGIC, CaGIC, CGIC) items at Weeks 4, 12,
24, 48, and 72
• Change in serum bile acid levels from baseline through Week 72
Background summary
In this investigational study, odevixibat is under development for treatment of
pruritus in patients with ALGS.
Currently, there is no approved medical therapy for the treatment of pruritus
in patients with ALGS. The majority of patients present with severe,
intractable pruritus, which can be disabling. Attempts at managing pruritus are
made by including ursodeoxycholic acid, cholestyramine, rifampin, ondansetron,
or naltrexone in the patient*s treatment regimen; these agents are at best
partially effective. Biliary diversion surgery is occasionally used to treat
intractable pruritus with some success. Treatment of persistent cholestasis and
progressive liver cirrhosis is supportive and usually includes a choleretic
agent. Kasai hepatoportoenterostomy (HPE) has been attempted to increase
biliary flow from the liver to the intestine, but unlike patients with biliary
atresia, those with ALGS who undergo the procedure have a worse outcome .
Approximately 15% to 25% of patients with ALGS will require a liver transplant
during childhood. For patients with ALGS there is a positive response to
transplant with about 90% of patients showing improvement in liver parameters
and some degree of catch-up growth. The 5-year survival post-transplant in this
population is about 80% .
By inhibiting IBAT with high selectivity and potency, odevixibat has the
potential to reduce the elevations in systemic bile acids that result from
cholestasis and decrease pruritus, thereby improving the health and wellbeing
of patients affected with ALGS. By reducing the elevations in systemic bile
acids, odevixibat also has the potential to improve liver function and modify
the progression of liver damage in patients with ALGS.
Study objective
This study has been transitioned to CTIS with ID 2023-509028-17-00 check the CTIS register for the current data.
To demonstrate a sustained effect of odevixibat on pruritus in patients with
ALGS who have completed study A4250-012 (ASSERT)
Study design
Phase 3, multi-center, open-label extension study
Intervention
Odevixibat (A4250), 120 µg/kg/day once daily, orally administered
Study burden and risks
See schedule of assessments on pages 20-23 of the protocol for more information.
Patient participation in this study will last approximately 76 weeks. During
this period, the patient will visit the hospital at least 10
times. The screening visit and the treatment visits last 2 - 6 hours.
During these visits, the following tests and procedures will take place:
- physical examination is performed and questions are asked about medical
history.
- weight, height, blood pressure, temperature and heart rate are measured
- blood and urine samples will be taken.
- The study doctor will also perform a pregnancy test on female subjects of
childbearing age.
- Subjects are asked to keep an eDiary
Possible side effects that are already known are described in the IB and
patient information letter.
Arvid Wallgrens backe 20
Göteborg 413 46
SE
Arvid Wallgrens backe 20
Göteborg 413 46
SE
Listed location countries
Age
Inclusion criteria
1. Completion of the 24-week Treatment Period of Study A4250-012;
2. Signed informed consent and assent as appropriate. Patients who turn 18
years of age (or legal age per country) during the study will be required to
re-consent to remain on the study;
3. Caregivers (and age-appropriate patients) must be willing and able to use an
electronic diary (eDiary) device as required by the study;
4. Sexually active males and females must agree to use a reliable contraceptive
method with <= 1% failure rate (such as intra-uterine device, or complete
abstinence) from signed informed consent through 90 days after last dose of
study drug;
Exclusion criteria
1. Decompensated liver disease, history or presence of clinically significant
ascites, variceal hemorrhage, and/or encephalopathy;
2. Patients who were not compliant with study drug treatment or procedures in
Study A4250-012;
3. Any other 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;
4. Known hypersensitivity to any components of odevixibat;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-509028-17-00 |
| EudraCT | EUCTR2021-000996-36-NL |
| CCMO | NL78174.042.21 |