Clinical trial NCT03566238: This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2
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 (PEDFIC 1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: PFIC1
PFIC2
Keywords: Pediatric
Cholestasis
Lead sponsor: AlbireoPharma
Sponsor class: UNKNOWN
First posted: 2018-06-25
Enrollment: 62
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-Blind, Randomized, Placebo-Controlled
Primary purpose: TREATMENT

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 progressive familial intrahepatic cholestasis (PFIC) types 1 and 2.

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

Eligibility criteria: Key Inclusion Criteria:

* A male or female participant with a clinical diagnosis of PFIC Type 1 or 2 and with a body weight above 5 kg
* Participant must have clinical genetic confirmation of PFIC-1 or PFIC-2
* Participant must have elevated serum bile acid (s-BA) concentration
* Participant must have history of significant pruritus and a caregiver reported observed scratching in the eDiary
* Participant and/or legal guardian must sign informed consent (and assent) as appropriate.
* Participants will be expected to have a consistent caregiver(s) for the duration of the study
* Caregivers and age-appropriate participants (≥8 years of age) must be willing and able to use an eDiary device as required by the study

Key Exclusion Criteria:

* Participant with pathologic variations of the ABCB11 gene that predict complete absence of the bile salt export pump (BSEP) protein
* Participant 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
* Participant with past medical history or ongoing chronic diarrhea
* Any participant with suspected or confirmed cancers except for basal cell carcinoma
* Participant 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
* Participant with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period
* Participant has had a liver transplant or a liver transplant is planned within 6 months of randomization
* Decompensated liver disease
* Participant suffers from uncontrolled, recalcitrant pruritic condition other than PFIC
* Participant who has been previously treated with an IBAT inhibitor whose pruritus has not responded to treatment

Primary outcomes:
measure: Proportion of Positive Pruritus Assessments at the Participant Level Over the 24-week Treatment Period Based on the Albireo Observer-reported Outcome (ObsRO) Instrument (United States Primary Endpoint)
timeFrame: Over 24 weeks of treatment
measure: Percentage of Participants Experiencing at Least a 70% Reduction in Fasting s-BA Concentration From Baseline to the End of Treatment or Reaching a Level <= 70 μmol/L After 24 Weeks of Treatment (European Union and Rest of the World Primary Endpoint)
timeFrame: Over 24 weeks of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - Presbyterian Hospital Building
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine - Texas Children's Liver Center
state: Texas
city: Melbourne
country: Australia
facility: The Royal Children's Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
city: Bron
country: France
facility: University and Pediatric Hospital of Lyon
city: le Kremlin Bicetre
country: France
facility: Universite Paris SUD - Hopitaux Universitaires Paris-Sud - Hopital Bicetre
city: Marseille
country: France
facility: Hospital de la Timone
city: Paris
country: France
facility: Hospital Necker-Enfants maladies
city: Essen
country: Germany
facility: Uniklinikum Essen- Kinderklinik II
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Tubingen
country: Germany
facility: Kinderklinik Tübingen, Universitätsklinikum Tübingen
city: Haifa
country: Israel
facility: Rambam Medical Centre
city: Jerusalem
country: Israel
facility: Shaare-Zedek Mc
city: Petach-Tikva
country: Israel
facility: Schneider Children's Medical Center Of Israel
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Padova
country: Italy
facility: University Hospital Of Padova
city: Torino
country: Italy
facility: Ospedale Regina Margherita
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum (UMC) Utrecht
city: Warsaw
country: Poland
facility: Instytut Pomnik - Centrum Zdrowia Dziecka
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Centre
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Solna
country: Sweden
facility: Astrid Lindgren Children's Hospital, Karolinska University Hospital
city: Ankara
country: Turkey
facility: Gazi University
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine
city: Antalya
country: Turkey
facility: Akdeniz University
city: Istanbul
country: Turkey
facility: Istanbul University Medical Faculty
city: Malatya
country: Turkey
facility: Inonu University Medical Faculty
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: Institute of Liver Studies - Kings College Hospital
Study officials:
References:
citation: Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz O, Fischler B, Gonzales E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Ozen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P. Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2022 Sep;7(9):830-842. doi: 10.1016/S2468-1253(22)00093-0. Epub 2022 Jul 1.