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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03659916




Registration number
NCT03659916
Ethics application status
Date submitted
24/08/2018
Date registered
6/09/2018

Titles & IDs
Public title
Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC
Scientific title
An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 2)
Secondary ID [1] 0 0
A4250-008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Progressive Familial Intrahepatic Cholestasis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - A4250 (odevixibat)

Experimental: A4250 - Capsules for oral administration (40 or 120 µg/kg) once daily for 72 weeks, or 40 µg/kg/day for the first 12 weeks followed by 120 µg/kg/day for the remaining 60 weeks"


Treatment: Drugs: A4250 (odevixibat)
A4250 is a small molecule and selective inhibitor of IBAT
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
US: Change in Pruritus
Timepoint [1] 0 0
From baseline over 72 weeks
Primary outcome [2] 0 0
EU and rest of world: Change in serum bile acids
Timepoint [2] 0 0
From baseline up to week 72
Secondary outcome [1] 0 0
EU and rest of world: Proportion of positive pruritus assessments at the patient level over the 72-week treatment period using the Albireo ObsRO instrument.
Timepoint [1] 0 0
72 weeks
Secondary outcome [2] 0 0
US: Change from baseline in serum bile acids after 72 weeks of treatment.
Timepoint [2] 0 0
72 weeks
Secondary outcome [3] 0 0
All regions: 3. Change from baseline in serum bile acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, 72, and 76
Timepoint [3] 0 0
Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, 72, and 76
Secondary outcome [4] 0 0
All regions: Proportion of individual assessments meeting the definition of a positive pruritus assessment at the patient level using the Albireo ObsRO instrument.
Timepoint [4] 0 0
weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, 0-70, or the proportion of positive pruritus assessments at each 4-week interval between V1/Screening and V5/Week 24, then by each visit between V5/Week 24 to V12/Week 76
Secondary outcome [5] 0 0
All regions: Proportion of individual AM assessments meeting the definition of a positive pruritus assessment at the patient level using the Albireo ObsRO instrument
Timepoint [5] 0 0
weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, 0-70, or the proportion of positive pruritus assessments at each 4-week interval between V1/Screening and V5/Week 24, then by each visit between V5/Week 24 to V12/Week 76
Secondary outcome [6] 0 0
All regions: Proportion of individual PM assessments meeting the definition of a positive pruritus assessment at the patient level using the Albireo ObsRO instrument
Timepoint [6] 0 0
weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, 0-70, or the proportion of positive pruritus assessments at each 4-week interval between V1/Screening and V5/Week 24, then by each visit between V5/Week 24 to V12/Week 76
Secondary outcome [7] 0 0
All regions. All-cause mortality
Timepoint [7] 0 0
From baseline to weeks 24, 48, and 72
Secondary outcome [8] 0 0
All regions: Number of patients undergoing biliary diversion surgery
Timepoint [8] 0 0
From baseline to weeks 24, 48, and 72
Secondary outcome [9] 0 0
All regions: Number of patients undergoing liver transplantation
Timepoint [9] 0 0
From baseline to weeks 24, 48, and 72
Secondary outcome [10] 0 0
All regions: Change in growth
Timepoint [10] 0 0
From baseline to weeks 24, 48, and 72
Secondary outcome [11] 0 0
All regions: Change in AST to platelet ratio idex (APRI) score
Timepoint [11] 0 0
From baseline to week 72
Secondary outcome [12] 0 0
All regions: Change in Fib-4 score
Timepoint [12] 0 0
From baseline to week 72
Secondary outcome [13] 0 0
All regions: Change in pediatric end-stage liver disease (PELD)/model for end-stage liver disease (MELD) score
Timepoint [13] 0 0
From baseline to week 72
Secondary outcome [14] 0 0
All regions: Change in use of antipruritic medication
Timepoint [14] 0 0
From baseline to weeks 24, 48, and 72

Eligibility
Key inclusion criteria
Inclusion Criteria Cohort 1:

1. Completion of the 24-week Treatment Period of Study A4250-005 or withdrawn from Study A4250-005 due to patient/caregiver judgment of intolerable symptoms after completing at least 12 weeks of treatment
2. Signed informed consent and assent as appropriate
3. Patients expected to have a consistent caregiver for the duration of the study
4. Caregivers (and age appropriate patients) must be willing and able to use an eDiary device as required by the study

Inclusion Criteria Cohort 2:

1. A male or female patient of any age, with a clinical diagnosis of PFIC, including episodic forms (i.e., BRIC), and with a body weight =5 kg at Visit S-1.
2. Patient must have clinical genetic confirmation of PFIC
3. Patients with PFIC, excluding BRIC, must have elevated serum bile acid concentration,specifically measured to be =100 µmol/L, taken as the average of 2 samples at least 7 days apart (Visits S-1 and S-2) prior to the Screening/Inclusion Visit (Visit 1).
4. Patients with PFIC, excluding BRIC, must have history of significant pruritus and a caregiver-reported observed scratching or patient-reported itching (for patients >18 with no caregiver-reported observed scratching) in the eDiary average of =2 (on 0 to 4 scale) in the 2 weeks prior to the Screening/Inclusion Visit (Visit 1).
5. Patients with episodic forms of PFIC (i.e., BRIC) must have an emerging flare characterized by clinically significant pruritus and elevated serum bile acid levels/cholestasis as judged by the investigator.
6. Patient and/or legal guardian must sign 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 in order to remain in the study.
7. Age appropriate patients are expected to have a consistent caregiver for the duration of the study
8. Caregivers and age-appropriate patients (=8 years of age) must be willing and able to use an eDiary device as required by the study
Minimum age
0 Months
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria Cohort 1:

1. Decompensated liver disease: coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
2. Sexually active males and females who are not using a reliable contraceptive method with =1% failure rate (such as hormonal contraception, intra-uterine device, or complete abstinence) throughout the duration of the study and 90 days thereafter
3. Patients not compliant with treatment in study A4250-005
4. Any other conditions or abnormalities which, in the opinion of the investigator or Medical Monitor, may compromise the safety of the patient, or interfere with the patient participating in or completing the study

Exclusion Criteria Cohort 2:

1. Known pathologic variations of the ABCB11 gene that have been demonstrated to result in complete absence of the BSEP protein
2. Patient with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following:

1. Biliary atresia of any kind
2. Suspected or proven liver cancer or metastasis to the liver on imaging studies
3. Histopathology on liver biopsy is suggestive of alternate non-PFIC related etiology of cholestasis Note: Patients with clinically significant portal hypertension are allowed.
3. Patient with a past medical history or ongoing presence of any other disease or condition known to interfere with the absorption, distribution, metabolism (specifically bile acid metabolism), or excretion of drugs in the intestine, including but not limited to,inflammatory bowel disease.
4. Patient with past medical history or ongoing chronic (i.e., >3 months) diarrhea requiring intravenous fluid or nutritional intervention for treatment of the diarrhea and/or its sequelae.
5. Patient has a confirmed past diagnosis of infection with human immunodeficiency virus or other present and active, clinically significant, acute, or chronic infection, or past medical history of any major episode of infection requiring hospitalization or treatment with parenteral anti-infective treatment within 4 weeks of treatment start (Study Day 1) or completion of oral anti-infective treatment within 2 weeks prior to start of Screening Period.
6. Any patient with suspected or confirmed cancers except for basal cell carcinoma, and non-liver cancers treated at least 5 years prior to Screening with no evidence of recurrence.
7. Patient has had a liver transplant, or a liver transplant is planned within 6 months of the Screening/Inclusion Visit.
8. Decompensated liver disease, coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
9. INR >1.4 (the patient may be treated with Vitamin K intravenously, and if INR is =1.4 at resampling the patient may be included).
10. Serum ALT >10 × upper limit of normal (ULN) at Screening.
11. Serum ALT >15 × ULN at any time point during the last 6 months unless an alternate etiology was confirmed for the elevation.
12. Total bilirubin >10 × ULN at Screening.
13. Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC.

Examples include, but not limited to, refractory atopic dermatitis or other primary pruritic skin diseases.
14. Any patient who is pregnant or lactating or who is planning to become pregnant within 72 weeks of the Screening/Inclusion Visit.
15. Sexually active males and females who are not using a reliable contraceptive method with =1% failure rate (such as hormonal contraception, intrauterine device, or complete abstinence) throughout the duration of the study and 90 days thereafter (from signed informed consent through 90 days after last dose of study drug).
16. Patient with a past medical history of alcohol or substance abuse will be excluded. Patient must agree to refrain from illicit drug and alcohol use during the study.
17. Administration of bile acid or lipid binding resins and medications that slow GI motility.
18. Patient has had investigational exposure to a drug, biologic agent, or medical device within 30 days prior to Screening, or 5 half-lives of the study agent, whichever is longer.
19. Any other conditions or abnormalities which, in the opinion of the investigator or Medical Monitor, may compromise the safety of the patient, or interfere with the patient participating in or completing the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
Accrual to date
Final
116
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Belgium
State/province [10] 0 0
Woluwe-Saint-Lambert
Country [11] 0 0
Canada
State/province [11] 0 0
Toronto
Country [12] 0 0
France
State/province [12] 0 0
Bron
Country [13] 0 0
France
State/province [13] 0 0
Le Kremlin-Bicêtre
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Germany
State/province [16] 0 0
Hannover
Country [17] 0 0
Germany
State/province [17] 0 0
Tübingen
Country [18] 0 0
Israel
State/province [18] 0 0
Jerusalem
Country [19] 0 0
Israel
State/province [19] 0 0
Petach-Tikva
Country [20] 0 0
Italy
State/province [20] 0 0
Bergamo
Country [21] 0 0
Italy
State/province [21] 0 0
Padova
Country [22] 0 0
Italy
State/province [22] 0 0
Torino
Country [23] 0 0
Netherlands
State/province [23] 0 0
Groningen
Country [24] 0 0
Netherlands
State/province [24] 0 0
Utrecht
Country [25] 0 0
Poland
State/province [25] 0 0
Warsaw
Country [26] 0 0
Saudi Arabia
State/province [26] 0 0
Riyadh
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Sweden
State/province [29] 0 0
Solna
Country [30] 0 0
Turkey
State/province [30] 0 0
Ankara
Country [31] 0 0
Turkey
State/province [31] 0 0
Antalya
Country [32] 0 0
Turkey
State/province [32] 0 0
Istanbul
Country [33] 0 0
Turkey
State/province [33] 0 0
Malatya
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Birmingham
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Leeds
Country [36] 0 0
United Kingdom
State/province [36] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Albireo, an Ipsen Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
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.
Available to whom?
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/members/ourmembers


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03659916