Biliary AtresiaPhase 2CARENCT05321524
Obeticholic Acid in Pediatric Subjects With Biliary Atresia
A Phase 2 study testing OCA 0.1mg, OCA 1.5mg and OCA 5mg in people with Biliary Atresia, run by Intercept Pharmaceuticals at 17 sites in 9 countries.
Trial summary
This is a Phase 2, multicenter, open-label, single dose and multi-dose, dose-finding study with an optional open-label extension (OLE) to assess the safety, tolerability, and pharmacokinetics of obeticholic acid (OCA) in pediatric subjects with biliary atresia with successful hepatoportoenterostomy (HPE, also known as… Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Biliary Atresia
- What is being tested?
- OCA 0.1mg, OCA 1.5mg and OCA 5mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 17 sitesin 9 countries
- Study dates
- 1 Jul 2015to 9 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female pediatric subjects ≥2 to <18 years old
- Diagnosis of biliary atresia
- Demonstrated successful HPE (also known as Kasai portoenterostomy) as defined by total bilirubin <2 mg/dL (34.2 μmol/L) at least 3 months post-HPE procedure.
- Able to swallow tablets (ie, tablet or mini-tablet formulation)
Who cannot join
- Prior liver transplant or active status on transplant list
- Conjugated (direct) bilirubin ≥ULN of site specific reference range
- If conjugated bilirubin is not available: total bilirubin ≥2 mg/dL (34.2 μmol/L)
- Platelets <150,000/μL
- INR ≥1.5
- Current or history of complications of decompensated chronic liver disease including:
Show all 23Show fewer
- high-risk gastroesophageal varices and/or variceal bleeding
- clinically evident ascites related to portal hypertension
- hepatic encephalopathy
- prior placement of portosystemic shunt
- hepatopulmonary syndrome or portopulmonary hypertension
- hepatorenal syndrome
- Current intractable pruritus or requires systemic treatment for pruritus within 3 months of Screening (e.g., with bile acid sequestrants or rifampicin)
- Height and weight Z-score <-2 per site specific ranges
- Acholic (pale) stools
- AST >4x ULN
- ALT >4x ULN
- GGT >500 U/L
- Anticoagulation therapy
- Albumin <3.5 g/dL
- Ongoing current cholangitis
- Choledochal cystic disease
- Renal disease defined as serum creatinine >ULN for subject's age, prior to enrollment
Trial locations and contacts
17 sites in 9 countries.
17 sites in 9 countries
France4 sites
CHU Lille
Lille, ME, 59037
Hopital de la Timone
Marseille, PACA, 13385
APHP- Hopital Necker Enfants Malades
Paris, 75015
CHU de Toulouse Purpan-Hopital des Enfants
Toulouse, 31059
Israel4 sites
Soroka University Medical Center
Beersheba, 84101
Shaare-Zedek Medical Center
Jerusalem, 9103102
Hadassah Medical Center
Jerusalem, 91120
Schneider Children's Medical Center
Petah Tikva, 4920235
Italy2 sites
Centre for Paediatric Hepatology
Bergamo, 24127
Regina Margherita Children's Hospital
Turin, 10126
Spain2 sites
Passeig Vall d'Hebron
Barcelona
Hospital Materno-Infantil de Malaga
Málaga
Germany1 site
Hannover Medical School, Children's Hospital, Paediatric Gastroenterology and Hepatology,
Hanover, Lower Saxony, 30625
Netherlands1 site
University Medical Center Gröningen-Beatrix, children's Hospital
Groningen, 9713 GZ
United Kingdom1 site
Birmingham Children's Hospital
Birmingham, West Midlands, B4 6NH
About this study
Official title: A Multicenter, Open-Label, Single- and Multiple-Dose, Dose-Finding Study, With an Optional Open-Label Extension to Assess the Safety, Tolerability, and Pharmacokinetics of Obeticholic Acid in Pediatric Subjects With Biliary Atresia
This is a Phase 2, multicenter, open-label, single dose and multi-dose, dose-finding study with an optional open-label extension (OLE) to assess the safety, tolerability, and pharmacokinetics of obeticholic acid (OCA) in pediatric subjects with biliary atresia with successful hepatoportoenterostomy (HPE, also known as a Kasai portoenterosomy). The OLE will continue to evaluate safety, tolerability, pharmacodynamics, and efficacy of OCA. In addition, a change in vitamin A and D levels, and where possible the degree of change in liver stiffness, will be assessed during the OLE.
- Conditions
- Biliary Atresia
- Being tested
- OCA 0.1mg, OCA 1.5mg, OCA 5mg
- Keywords
- Biliary Atresia, hepatoportoenterostomy (HPE), Kasai portoenterostomy, Liver, Obeticholic Acid
- Medical subject headings
- Biliary Atresia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OCA 0.1mgDrug
Also called Obeticholic Acid, 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
Tablets administered orally once daily.
OCA 1.5mgDrug
Also called 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
Tablets administered orally once daily.
OCA 5mgDrug
Also called 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
Tablets administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA) | Experimental | At Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Enrollment in the Multiple Dose (MD) Phase will occur in a sequential fashion. At Day 28, the first 8 (±1) eligible subjects will be assigned to the Low Dose Cohort and will receive a 1.5 mg adult-equivalent dose of OCA daily for 4 weeks.
The adult-equivalent dose is based on a 70-kg adult. 2 OCA tablet dose strength (0.1mg and 1.5mg) are available in the study and dose will be determined using weight based dosing chart. Receives: Drug: OCA 0.1mg; Drug: OCA 1.5mg |
| SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA) | Experimental | At Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Upon safety and tolerability assessment in the Low Dose Cohort, 8 (±1) eligible subjects will be assigned to the Medium Dose Cohort and will receive a 5 mg adult-equivalent dose of OCA daily for 4 weeks.
The adult-equivalent dose is based on a 70-kg adult. 3 OCA tablet dose strength (0.1mg, 1.5mg and 5mg tablets) are available in the study and dose will be determined using weight based dosing chart. Receives: Drug: OCA 0.1mg; Drug: OCA 1.5mg; Drug: OCA 5mg |
| SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA) | Experimental | At Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Upon safety and tolerability assessment in the Medium Dose Cohort, 8 (±1) eligible subjects will be assigned to the High Dose Cohort and will receive a 10 mg adult-equivalent dose of OCA daily for 4 weeks.
The adult-equivalent dose is based on a 70-kg adult. 3 OCA tablet dose strength (0.1mg, 1.5mg and 5mg tablets) are available in the study and dose will be determined using weight based dosing chart. Receives: Drug: OCA 0.1mg; Drug: OCA 1.5mg; Drug: OCA 5mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)
Measured: Day 1, 21, and 56.
The plasma concentration of OCA and its conjugates (glyco-OCA and tauro-OCA)
Change in plasma concentrations of unconjugated OCA and its conjugates (glyco-OCA and tauro-OCA) will be quantitated, and total OCA concentration will be calculated in the SD and MD Phase.
Measured: Day 1, 21, and 56.
Secondary outcomes (7)
Biomarkers of FXR-activation: change from baseline of the plasma value of Fibroblast Growth Factor-19 (FGF-19)
Measured: Day 1, 21, and 56
Biomarkers of FXR-activation: change from baseline of the plasma value of 7-hydroxyl-4-cholesten-3-one (C4)
Measured: Day 1, 21, and 56
Biomarkers of FXR-activation: change from baseline of the plasma value of Endogenous Bile Acids
Measured: Day 1, 21, and 56
Biomarkers of hepatobiliary function: Alkaline Phosphatase (ALP)
Measured: Time Frame: Day 1, 21, and 56
Biomarkers of hepatobiliary function: Aspartate Aminotransferase (AST)
Measured: Time Frame: Day 1, 21, and 56
Biomarkers of hepatobiliary function: Alanine Aminotransferase (ALT)
Measured: Time Frame: Day 1, 21, and 56
Biomarkers of hepatobiliary function: Gamma-Glutamyl Transpeptidase (GGT)
Measured: Time Frame: Day 1, 21, and 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2022
- Study start1 Jul 2015
- Primary completion9 Mar 2023
- Study completion9 Mar 2023
Why it stopped: After extensive efforts to improve recruitment, it is deemed not feasible to enroll the requisite number of subjects to generate data needed to meet the study objectives. EMA Paediatric Committee agreed with the Sponsor to terminate this study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Biliary AtresiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intercept Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lynda Szczech, MD, Study director, Intercept Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05321524
- Sponsor's protocol ID
- 747-206
- Acronym
- CARE
- Status last verified
- Mar 2023
- First submitted
- 18 Mar 2022
- Last updated
- 28 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, Single- and Multiple-Dose, Dose-Finding Study, With an Optional Open-Label Extension to Assess the Safety, Tolerability, and Pharmacokinetics of Obeticholic Acid in Pediatric Subjects With Biliary Atresia
- ClinicalTrials.gov ID
- NCT05321524
- Acronym / sponsor ID
- CARE / 747-206
- Conditions
- Biliary Atresia
- Keywords
- Biliary Atresia, hepatoportoenterostomy (HPE), Kasai portoenterostomy, Liver, Obeticholic Acid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After extensive efforts to improve recruitment, it is deemed not feasible to enroll the requisite number of subjects to generate data needed to meet the study objectives. EMA Paediatric Committee agreed with the Sponsor to terminate this study.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Intercept PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2015 (actual)
- Primary completion
- 9 Mar 2023 (actual)
- Study completion
- 9 Mar 2023 (actual)
- First posted
- 11 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, multicenter, open-label, single dose and multi-dose, dose-finding study with an optional open-label extension (OLE) to assess the safety, tolerability, and pharmacokinetics of obeticholic acid (OCA) in pediatric subjects with biliary atresia with successful hepatoportoenterostomy (HPE, also known as a Kasai portoenterosomy). The OLE will continue to evaluate safety, tolerability, pharmacodynamics, and efficacy of OCA. In addition, a change in vitamin A and D levels, and where possible the degree of change in liver stiffness, will be assessed during the OLE.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA) | Experimental | Drug: OCA 0.1mg, Drug: OCA 1.5mgAt Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Enrollment in the Multiple Dose (MD) Phase will occur in a sequential fashion. At Day 28, the first 8 (±1) eligible subjects will be assigned to the Low Dose Cohort and will receive a 1.5 mg adult-equivalent dose of OCA daily for 4 weeks. The adult-equivalent dose is based on a 70-kg adult. 2 OCA tablet dose strength (0.1mg and 1.5mg) are available in the study and dose will be determined using weight based dosing chart. |
| SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA) | Experimental | Drug: OCA 0.1mg, Drug: OCA 1.5mg, Drug: OCA 5mgAt Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Upon safety and tolerability assessment in the Low Dose Cohort, 8 (±1) eligible subjects will be assigned to the Medium Dose Cohort and will receive a 5 mg adult-equivalent dose of OCA daily for 4 weeks. The adult-equivalent dose is based on a 70-kg adult. 3 OCA tablet dose strength (0.1mg, 1.5mg and 5mg tablets) are available in the study and dose will be determined using weight based dosing chart. |
| SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA) | Experimental | Drug: OCA 0.1mg, Drug: OCA 1.5mg, Drug: OCA 5mgAt Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Upon safety and tolerability assessment in the Medium Dose Cohort, 8 (±1) eligible subjects will be assigned to the High Dose Cohort and will receive a 10 mg adult-equivalent dose of OCA daily for 4 weeks. The adult-equivalent dose is based on a 70-kg adult. 3 OCA tablet dose strength (0.1mg, 1.5mg and 5mg tablets) are available in the study and dose will be determined using weight based dosing chart. |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Male or female pediatric subjects ≥2 to <18 years old
- Diagnosis of biliary atresia
- Demonstrated successful HPE (also known as Kasai portoenterostomy) as defined by total bilirubin <2 mg/dL (34.2 μmol/L) at least 3 months post-HPE procedure.
- Able to swallow tablets (ie, tablet or mini-tablet formulation)
Key exclusion criteria (23 listed)
- Prior liver transplant or active status on transplant list
- Conjugated (direct) bilirubin ≥ULN of site specific reference range
- If conjugated bilirubin is not available: total bilirubin ≥2 mg/dL (34.2 μmol/L)
- Platelets <150,000/μL
- INR ≥1.5
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OCA 0.1mgAlso: Obeticholic Acid, 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747Tablets administered orally once daily. | Drug | SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA) |
| OCA 1.5mgAlso: 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747Tablets administered orally once daily. | Drug | SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA) |
| OCA 5mgAlso: 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747Tablets administered orally once daily. | Drug | SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA) |
Primary outcome
Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)
Time frame: Day 1, 21, and 56.
The plasma concentration of OCA and its conjugates (glyco-OCA and tauro-OCA)
Time frame: Day 1, 21, and 56.
Change in plasma concentrations of unconjugated OCA and its conjugates (glyco-OCA and tauro-OCA) will be quantitated, and total OCA concentration will be calculated in the SD and MD Phase.
7 secondary outcomes
Biomarkers of FXR-activation: change from baseline of the plasma value of Fibroblast Growth Factor-19 (FGF-19)
Time frame: Day 1, 21, and 56
Biomarkers of FXR-activation: change from baseline of the plasma value of 7-hydroxyl-4-cholesten-3-one (C4)
Time frame: Day 1, 21, and 56
Biomarkers of FXR-activation: change from baseline of the plasma value of Endogenous Bile Acids
Time frame: Day 1, 21, and 56
Biomarkers of hepatobiliary function: Alkaline Phosphatase (ALP)
Time frame: Time Frame: Day 1, 21, and 56
Biomarkers of hepatobiliary function: Aspartate Aminotransferase (AST)
Time frame: Time Frame: Day 1, 21, and 56
Biomarkers of hepatobiliary function: Alanine Aminotransferase (ALT)
Time frame: Time Frame: Day 1, 21, and 56
Biomarkers of hepatobiliary function: Gamma-Glutamyl Transpeptidase (GGT)
Time frame: Time Frame: Day 1, 21, and 56
Results and safety
The study was stopped early (reason given: After extensive efforts to improve recruitment, it is deemed not feasible to enroll the requisite number of subjects to generate data needed to meet the study objectives. EMA Paediatric Committee agreed with the Sponsor to terminate this study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynda Szczech, MD study director
Intercept Pharmaceuticals
17 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OCA 0.1mg, OCA 1.5mg and OCA 5mg in people with Biliary Atresia, run by Intercept Pharmaceuticals at 17 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in France, Israel, Italy, Spain, Belgium and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: After extensive efforts to improve recruitment, it is deemed not feasible to enroll the requisite number of subjects to generate data needed to meet the study objectives. EMA Paediatric Committee agreed with the Sponsor to terminate this study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) (time frame: Day 1, 21, and 56.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2023.