search
Back to results

Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC

Primary Purpose

Progressive Familial Intrahepatic Cholestasis

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
A4250 (odevixibat)
Sponsored by
Albireo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Progressive Familial Intrahepatic Cholestasis focused on measuring Pediatric, Cholestasis

Eligibility Criteria

0 Months - 100 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 Completion of the 24-week Treatment Period of Study A4250-005 or withdrawn from Study A4250-005 due to patient/caregiver judgment of intolerable symptoms after completing at least 12 weeks of treatment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

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.

Sites / Locations

  • Children's Hospital Los Angeles
  • Children's Hospital Colorado
  • Emory University School of Medicine
  • Riley Hospital for Children - Riley Children's Specialists
  • Johns Hopkins School of Medicine
  • Washington University School of Medicine
  • Icahn School of Medicine at Mount Sinai
  • Columbia University Medical Center - Presbyterian Hospital Building
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh
  • Baylor College of Medicine - Texas Children's Liver Center
  • The Royal Children's Hospital
  • Cliniques Universitaires Saint-Luc
  • The Hospital for Sick Children
  • University and Pediatric Hospital of Lyon
  • Universite Paris SUD - Hpitaux Universitaires Paris-Sud - Hopital Bicetre
  • Hospital De La Timone
  • Hospital Necker-Enfants Maladies
  • Medizinische Hochschule Hannover
  • Kinderklinik Tubingen, Universitatsklinikum Tubingen
  • Univesitatsklinikum Tubingen Klinik fur Kinder und Jugendmedizin
  • Shaare-Zedek Mc
  • Schneider Children's Medical Center Of Israel
  • Azienda Ospedaliera Papa Giovanni XXIII
  • University Hospital Of Padova
  • Ospedale Regina Margherita
  • University Medical Center Groningen
  • Universitair Medisch Centrum (UMC) Utrecht
  • Instytut Pomnik - Centrum Zarowia Dziecka
  • King Faisal Specialist Hospital & Research Centre
  • Hospital Universitari Vall d'Hebron
  • Hospital Universitario La Paz
  • Astrid Lindgren Children's Hospital, Karolinska University Hospital
  • Gazi University
  • Hacettepe University Faculty of Medicine
  • Akdeniz University
  • Istanbul University Medical Faculty
  • Inonu University Medical Faculty
  • Birmingham Women's and Children's NHS Foundation Trust
  • Leeds General Infirmary
  • Institute of Liver Studies - Kings College Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A4250

Arm Description

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"

Outcomes

Primary Outcome Measures

Change in Pruritus
Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching
Change in serum bile acids

Secondary Outcome Measures

All-cause mortality
Number of patients undergoing biliary diversion surgery
Number of patients undergoing liver transplantation
Change in growth
The linear growth deficit compared to the standard growth curve
Change in AST to platelet ratio idex (APRI) score
Change in Fib-4 score
Change in pediatric end-stage liver disease (PELD)/model for end-stage liver disease (MELD) score
Change in use of antipruritic medication

Full Information

First Posted
August 24, 2018
Last Updated
July 13, 2023
Sponsor
Albireo
search

1. Study Identification

Unique Protocol Identification Number
NCT03659916
Brief Title
Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC
Official 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)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 28, 2018 (Actual)
Primary Completion Date
March 30, 2024 (Anticipated)
Study Completion Date
May 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Albireo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Open Label Extension Study to evaluate long term safety and persistence of effect of A4250 in children with PFIC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Familial Intrahepatic Cholestasis
Keywords
Pediatric, Cholestasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A4250
Arm Type
Experimental
Arm Description
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"
Intervention Type
Drug
Intervention Name(s)
A4250 (odevixibat)
Intervention Description
A4250 is a small molecule and selective inhibitor of IBAT
Primary Outcome Measure Information:
Title
Change in Pruritus
Description
Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching
Time Frame
From baseline over 72 weeks
Title
Change in serum bile acids
Time Frame
From baseline up to week 72
Secondary Outcome Measure Information:
Title
All-cause mortality
Time Frame
From baseline to weeks 24, 48, and 72
Title
Number of patients undergoing biliary diversion surgery
Time Frame
From baseline to weeks 24, 48, and 72
Title
Number of patients undergoing liver transplantation
Time Frame
From baseline to weeks 24, 48, and 72
Title
Change in growth
Description
The linear growth deficit compared to the standard growth curve
Time Frame
From baseline to weeks 24, 48, and 72
Title
Change in AST to platelet ratio idex (APRI) score
Time Frame
From baseline to week 72
Title
Change in Fib-4 score
Time Frame
From baseline to week 72
Title
Change in pediatric end-stage liver disease (PELD)/model for end-stage liver disease (MELD) score
Time Frame
From baseline to week 72
Title
Change in use of antipruritic medication
Time Frame
From baseline to weeks 24, 48, and 72

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Months
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Cohort 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 Signed informed consent and assent as appropriate Patients expected to have a consistent caregiver for the duration of the study Caregivers (and age appropriate patients) must be willing and able to use an eDiary device as required by the study Inclusion Criteria Cohort 2: 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. Patient must have clinical genetic confirmation of PFIC 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). 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). 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. 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. Age appropriate patients are expected to have a consistent caregiver for the duration of the study Caregivers and age-appropriate patients (≥8 years of age) must be willing and able to use an eDiary device as required by the study Exclusion Criteria Cohort 1: Decompensated liver disease: coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy 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 Patients not compliant with treatment in study A4250-005 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: Known pathologic variations of the ABCB11 gene that have been demonstrated to result in complete absence of the BSEP protein Patient with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following: Biliary atresia of any kind Suspected or proven liver cancer or metastasis to the liver on imaging studies Histopathology on liver biopsy is suggestive of alternate non-PFIC related etiology of cholestasis Note: Patients with clinically significant portal hypertension are allowed. 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. 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. 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. 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. Patient has had a liver transplant, or a liver transplant is planned within 6 months of the Screening/Inclusion Visit. Decompensated liver disease, coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy 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). Serum ALT >10 × upper limit of normal (ULN) at Screening. Serum ALT >15 × ULN at any time point during the last 6 months unless an alternate etiology was confirmed for the elevation. Total bilirubin >10 × ULN at Screening. 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. Any patient who is pregnant or lactating or who is planning to become pregnant within 72 weeks of the Screening/Inclusion Visit. 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). 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. Administration of bile acid or lipid binding resins and medications that slow GI motility. 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. 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.
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Riley Hospital for Children - Riley Children's Specialists
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Johns Hopkins School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center - Presbyterian Hospital Building
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Baylor College of Medicine - Texas Children's Liver Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Royal Children's Hospital
City
Melbourne
Country
Australia
Facility Name
Cliniques Universitaires Saint-Luc
City
Woluwe-Saint-Lambert
Country
Belgium
Facility Name
The Hospital for Sick Children
City
Toronto
Country
Canada
Facility Name
University and Pediatric Hospital of Lyon
City
Bron
Country
France
Facility Name
Universite Paris SUD - Hpitaux Universitaires Paris-Sud - Hopital Bicetre
City
Le Kremlin-Bicêtre
Country
France
Facility Name
Hospital De La Timone
City
Marseille
Country
France
Facility Name
Hospital Necker-Enfants Maladies
City
Paris
Country
France
Facility Name
Medizinische Hochschule Hannover
City
Hannover
Country
Germany
Facility Name
Kinderklinik Tubingen, Universitatsklinikum Tubingen
City
Tübingen
Country
Germany
Facility Name
Univesitatsklinikum Tubingen Klinik fur Kinder und Jugendmedizin
City
Tübingen
Country
Germany
Facility Name
Shaare-Zedek Mc
City
Jerusalem
Country
Israel
Facility Name
Schneider Children's Medical Center Of Israel
City
Petach-Tikva
Country
Israel
Facility Name
Azienda Ospedaliera Papa Giovanni XXIII
City
Bergamo
Country
Italy
Facility Name
University Hospital Of Padova
City
Padova
Country
Italy
Facility Name
Ospedale Regina Margherita
City
Torino
Country
Italy
Facility Name
University Medical Center Groningen
City
Groningen
Country
Netherlands
Facility Name
Universitair Medisch Centrum (UMC) Utrecht
City
Utrecht
Country
Netherlands
Facility Name
Instytut Pomnik - Centrum Zarowia Dziecka
City
Warsaw
Country
Poland
Facility Name
King Faisal Specialist Hospital & Research Centre
City
Riyadh
Country
Saudi Arabia
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Facility Name
Astrid Lindgren Children's Hospital, Karolinska University Hospital
City
Solna
Country
Sweden
Facility Name
Gazi University
City
Ankara
Country
Turkey
Facility Name
Hacettepe University Faculty of Medicine
City
Ankara
Country
Turkey
Facility Name
Akdeniz University
City
Antalya
Country
Turkey
Facility Name
Istanbul University Medical Faculty
City
Istanbul
Country
Turkey
Facility Name
Inonu University Medical Faculty
City
Malatya
Country
Turkey
Facility Name
Birmingham Women's and Children's NHS Foundation Trust
City
Birmingham
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds
Country
United Kingdom
Facility Name
Institute of Liver Studies - Kings College Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC

We'll reach out to this number within 24 hrs