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This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC 1 or 2 (PEDFIC 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03566238
Recruitment Status : Active, not recruiting
First Posted : June 25, 2018
Last Update Posted : March 5, 2020
Sponsor:
Information provided by (Responsible Party):
Albireo

Tracking Information
First Submitted Date  ICMJE May 25, 2018
First Posted Date  ICMJE June 25, 2018
Last Update Posted Date March 5, 2020
Actual Study Start Date  ICMJE May 16, 2018
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2018)
  • Change in pruritus (US) [ Time Frame: From baseline over the last 5 months of the treatment period ]
    Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching compared to placebo
  • Bile acid reduction (EU and rest of world) [ Time Frame: From baseline to Week 24 ]
    Bile acid responder rate on treatment compared to the placebo group
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2018)
  • Change in pruritus (US) [ Time Frame: From baseline to Week 24 ]
    Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching compared to placebo
  • Bile acid reduction (EU and rest of world) [ Time Frame: From randomization to Week 24 ]
    Bile acid responder rate on treatment compared to the placebo group
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2019)
  • Bile acid reduction (US) [ Time Frame: From baseline to Week 24 ]
    Bile acid responder rate on treatment compared to the placebo group
  • Change in pruritus (EU and rest of world) [ Time Frame: From baseline over the last 5 months of the treatment period ]
    Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching compared to placebo
  • Change in fasting serum bile acids (s-BA) [ Time Frame: From baseline to Week 24 ]
  • Change in serum ALT concentration [ Time Frame: From baseline to Week 24 ]
  • Change in growth [ Time Frame: From baseline to Week 24 ]
    defined as the linear deficit (weight for age and body mass index) compared to the standard growth curves (Z-score, standard deviation from P50)
  • Proportion of patients achieving meaningful reduction in caregiver-reported observed scratching [ Time Frame: From baseline over the last 5 months of the treatment period ]
  • Change in sleep disturbances [ Time Frame: From baseline over the last 5 months of the treatment period ]
    measured with the Albireo PRO instrument
  • Change in sleep disturbances, including number of awakenings [ Time Frame: From baseline over the last 5 months of the treatment period ]
    measured with the ObsRO instrument
  • Change in patient-reported itch severity [ Time Frame: From baseline over the last 5 months of the treatment period ]
    measured by the average daily score of the Albireo PRO instrument
  • Number of patients undergoing biliary diversion surgery or liver transplantation [ Time Frame: From randomization to week 24 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2018)
  • Bile acid reduction (US) [ Time Frame: From randomization to Week 24 ]
    Bile acid responder rate on treatment compared to the placebo group
  • Change in pruritus (EU and rest of world) [ Time Frame: From baseline to Week 24 ]
    Change in pruritus as indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching compared to placebo
  • Change in fasting serum bile acids (s-BA) [ Time Frame: From baseline to Week 24 ]
  • Change in serum ALT concentration [ Time Frame: From baseline to Week 24 ]
  • Change in growth [ Time Frame: From baseline to Week 24 ]
    defined as the linear deficit (weight for age and body mass index) compared to the national growth curves (Z-score, standard deviation from P50)
  • Proportion of patients achieving meaningful reduction in caregiver-reported observed scratching [ Time Frame: From baseline to Week 24 ]
  • Change in sleep disturbances [ Time Frame: From baseline to Week 24 ]
    measured with the Albireo PRO instrument
  • Change in sleep disturbances, including number of awakenings [ Time Frame: From baseline to Week 24 ]
    measured with the ObsRO instrument
  • Change in patient-reported itch severity [ Time Frame: From baseline to Week 24 ]
    measured by the average daily score of the Albireo PRO instrument
  • Number of patients undergoing biliary diversion surgery or being listed for liver transplantation [ Time Frame: From randomization to week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC 1 or 2
Official Title  ICMJE A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study to Demonstrate Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 1)
Brief Summary Double blind, randomized, placebo controlled, Phase 3 study to investigate the efficacy and safety of low doses and high doses of A4250 compared to placebo in children with PFIC (deficiencies of familial intrahepatic cholestasis-1 or bile salt export pump).
Detailed Description

Up to 50 sites in the following countries will take part in this study:

Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States, and Saudi Arabia

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-Blind, Randomized, Placebo-Controlled
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • PFIC1
  • PFIC2
Intervention  ICMJE
  • Drug: A4250 (odevixibat)
    A4250 is a small molecule and selective inhibitor of IBAT.
  • Drug: Placebo
    Placebo identical in appearance to active drug (A4250)
Study Arms  ICMJE
  • Experimental: A4250 low dose
    Capsules for oral administration (40 ug/kg) once daily for 24 weeks
    Intervention: Drug: A4250 (odevixibat)
  • Experimental: A4250 high dose
    Capsules for oral administration (120 ug/kg) once daily for 24 weeks
    Intervention: Drug: A4250 (odevixibat)
  • Placebo Comparator: Placebo
    Capsules for oral administration (to match active) once daily for 24 weeks
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 4, 2020)
62
Original Estimated Enrollment  ICMJE
 (submitted: June 20, 2018)
60
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • A male or female patient with a clinical diagnosis of PFIC Type 1 or 2 and with a body weight above 5 kg
  • Patient must have clinical genetic confirmation of PFIC-1 or PFIC-2
  • Patient must have elevated s-BA concentration
  • Patient must have history of significant pruritus and a caregiver reported observed scratching in the eDiary
  • Patient and/or legal guardian must sign informed consent (and assent) as appropriate.
  • Patients will be expected to have a consistent caregiver(s) 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

Key Exclusion Criteria:

  • Patient with pathologic variations of the ABCB11 gene that predict 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:

    1. Biliary atresia of any kind
    2. Benign recurrent intrahepatic cholestasis, indicated by any history of normal s BAs
    3. Suspected or proven liver cancer or metastasis to the liver on imaging studies
    4. Histopathology on liver biopsy that is suggestive of alternate non-PFIC related etiology of cholestasis
  • Patient with past medical history or ongoing chronic diarrhea
  • Any patient with suspected or confirmed cancers except for basal cell carcinoma
  • Patient with a past medical history of chronic kidney disease with an impaired renal function and a glomerular filtration rate <70 mL/min/1.73 m^2
  • Patient with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period
  • Patient has had a liver transplant or a liver transplant is planned within 6 months of randomization
  • Decompensated liver disease
  • Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC
  • Patient who has been previously treated with an IBAT inhibitor whose pruritus has not responded to treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Israel,   Italy,   Netherlands,   Poland,   Saudi Arabia,   Spain,   Sweden,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03566238
Other Study ID Numbers  ICMJE A4250-005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Albireo
Study Sponsor  ICMJE Albireo
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Albireo
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP