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This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC 1 or 2 (PEDFIC1)

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ClinicalTrials.gov Identifier: NCT03566238
Recruitment Status : Recruiting
First Posted : June 25, 2018
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Albireo

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).

Condition or disease Intervention/treatment Phase
PFIC1 PFIC2 Drug: A4250 Drug: Placebo Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-Blind, Randomized, Placebo-Controlled
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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 (PEDFIC1)
Actual Study Start Date : May 16, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: A4250 low dose
Capsules for oral administration (40 ug/kg) once daily for 24 weeks
Drug: A4250
A4250 is a small molecule and selective inhibitor of IBAT.

Experimental: A4250 high dose
Capsules for oral administration (120 ug/kg) once daily for 24 weeks
Drug: A4250
A4250 is a small molecule and selective inhibitor of IBAT.

Placebo Comparator: Placebo
Capsules for oral administration (to match active) once daily for 24 weeks
Drug: Placebo
Placebo identical in appearance to active drug (A4250)




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. Bile acid reduction (US) [ Time Frame: From baseline to Week 24 ]
    Bile acid responder rate on treatment compared to the placebo group

  2. 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

  3. Change in fasting serum bile acids (s-BA) [ Time Frame: From baseline to Week 24 ]
  4. Change in serum ALT concentration [ Time Frame: From baseline to Week 24 ]
  5. 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)

  6. Proportion of patients achieving meaningful reduction in caregiver-reported observed scratching [ Time Frame: From baseline over the last 5 months of the treatment period ]
  7. Change in sleep disturbances [ Time Frame: From baseline over the last 5 months of the treatment period ]
    measured with the Albireo PRO instrument

  8. 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

  9. 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

  10. Number of patients undergoing biliary diversion surgery or being listed for liver transplantation [ Time Frame: From randomization to week 24 ]


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Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 excluding those who have undergone a successful reversal procedure that has permanently restored flow of bile acids from the liver to the duodenum
  • Patient has had a liver transplant or listed for liver transplant, excluding those who have been listed for transplant for pruritus who have since been removed from the transplant list
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03566238


Contacts
Contact: Albireo (857) 254-5555 medinfo@albireopharma.com

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Sponsors and Collaborators
Albireo

Responsible Party: Albireo
ClinicalTrials.gov Identifier: NCT03566238     History of Changes
Other Study ID Numbers: A4250-005
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019

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

Keywords provided by Albireo:
Pediatric
Cholestasis