Clinical trial • Phase III • Rare Disease

odevixibat for Alagille syndrome

Phase III trial of odevixibat for Alagille syndrome. open-label, none/not specified-controlled. 25 participants.

Overview

Trial Therapeutic Area
Rare Disease
Trial Disease
Alagille syndrome
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
20-12-2023
First CTIS Authorization Date
07-02-2024

Trial design

open-label, none/not specified-controlled Phase III trial in Belgium, Netherlands, France and others.

Open Label
Yes
Comparator
None/Not specified
Target Sample Size
25
Trial Duration For Participant
504

Eligibility

Recruits 25 paediatric patients.

Vulnerable Population
Vulnerable populations included children; informed consent and assent procedures are specified. The protocol requires "Signed informed consent and assent as appropriate." Age-specific participant information and consent/assent forms are provided (adult, parent/guardian, adolescent assent 12-17, assent 6-11, pregnant partner forms) in multiple languages (English, Dutch, French, Polish, Italian as available in site documents). Patients who reach legal adulthood during the study must re-consent to remain on study. Caregivers (and age-appropriate patients) must be willing and able to use an electronic diary (eDiary).

Inclusion criteria

  • {"criterion_text":"- 1. Completion of the 24-week Treatment Period of Study A4250-012\n- 2. Signed 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 to remain on the study\n- 3. Caregivers (and age-appropriate patients) must be willing and able to use an electronic diary (eDiary) device as required by the study\n- 4. Sexually active males and females must agree to use a reliable contraceptive method with ≤ 1% failure rate (such as intra-uterine device or complete abstinence) from signed informed consent through 90 days after last dose of study drug."}

Exclusion criteria

  • {"criterion_text":"- 1. Decompensated liver disease, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy\n- 2. Patients who were not compliant with study drug treatment or procedures in Study A4250-012\n- 3. Any other conditions or abnormalities which, in the opinion of the investigator, may compromise the safety of the patient, or interfere with the patient participating in or completing the study\n- 4. Known hypersensitivity to any components of odevixibat"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from baseline in scratching through Week 72 as measured by the Albireo ObsRO caregiver instrument.","definition_or_measurement_approach":"Change from baseline in scratching measured through Week 72 using the Albireo ObsRO (observer-reported outcome) caregiver instrument."}

Secondary endpoints

  • {"endpoint_text":"- • Change in serum bile acid levels from baseline to Week 72;","definition_or_measurement_approach":"Change in serum bile acid levels from baseline to Week 72 (laboratory measurement of serum bile acids)."}
  • {"endpoint_text":"- • Change from baseline through Week 72 in patient reported and observer reported itching and scratching severity scores, respectively, for the morning and evening assessment;","definition_or_measurement_approach":"Change from baseline through Week 72 in PRO and ObsRO itching and scratching severity scores for morning and evening assessments (patient- and observer-reported instruments)."}
  • {"endpoint_text":"- • Percentage of patients achieving a clinically meaningful decrease in pruritus (pruritus responders) at each visit as measured by the Albireo ObsRO/patient reported outcomes (PRO) instruments;","definition_or_measurement_approach":"Proportion of patients meeting predefined clinically meaningful decrease in pruritus at each visit as assessed by Albireo ObsRO and PRO instruments."}
  • {"endpoint_text":"- • Change from baseline to Week 72 in sleep parameters as measured with the Albireo ObsRO/PRO instruments (e.g. tiredness and number of awakenings);","definition_or_measurement_approach":"Change from baseline to Week 72 in sleep-related parameters (e.g. tiredness, number of awakenings) measured using Albireo ObsRO/PRO instruments."}
  • {"endpoint_text":"- • Change from baseline to Week 72 in Pediatric Quality of Life Inventory (PedsQL) scores","definition_or_measurement_approach":"Change from baseline to Week 72 in PedsQL (Pediatric Quality of Life Inventory) total and domain scores."}
  • {"endpoint_text":"- • Assessment of Global Symptom Relief from baseline to Weeks 4, 12, 24, 48, and 72 as measured by patient, caregiver, and clinician Global impression of Symptoms (PGIS, CaGIS, CGIS) items","definition_or_measurement_approach":"Global symptom relief assessed at Weeks 4, 12, 24, 48, and 72 using PGIS, CaGIS, and CGIS (patient, caregiver, clinician global impression of symptoms)."}
  • {"endpoint_text":"- • Assessment of Global Symptom Relief as measured by patient, caregiver, and clinician Global Impression of Change (PGIC, CaGIC, CGIC) items at Weeks 4, 12, 24, 48, and 72","definition_or_measurement_approach":"Global impression of change assessed at Weeks 4, 12, 24, 48, and 72 using PGIC, CaGIC, and CGIC instruments."}
  • {"endpoint_text":"- • Change in serum bile acid levels from baseline through Week 72","definition_or_measurement_approach":"Change in serum bile acid levels from baseline through Week 72 (laboratory measurement)."}

Recruitment

Planned Sample Size
25
Recruitment Window Months
63
Consent Approach
Signed informed consent required; assent obtained where appropriate. Specific mention: "Signed 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 to remain on the study." Age-specific information and consent/assent forms are provided (adult, parent/guardian, 12-17y assent, 6-11y assent), and documents are available in multiple languages (English, Dutch, French, Polish, Italian as provided in site-specific document list). Caregivers provide assistance and some instruments (eDiary) require caregiver or age-appropriate patient use.

Geography

Total Number Of Sites
12
Total Number Of Participants
35

Belgium

Earliest CTIS Part Ii Submission Date
19-01-2024
Latest Decision Or Authorization Date
18-08-2025
Processing Time Days
577
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Cliniques Universitaires Saint-Luc
Department Name
Paediatric Department
Principal Investigator Name
Xavier Stephenne
Principal Investigator Email
xavier.stephenne@saintluc.uclouvain.be
Contact Person Name
Xavier Stephenne

Netherlands

Earliest CTIS Part Ii Submission Date
19-01-2024
Latest Decision Or Authorization Date
20-08-2025
Processing Time Days
579
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Universitair Medisch Centrum Groningen
Department Name
Pediatric Gastro/Hepatology, Department Pediatrics
Principal Investigator Name
Hendrik Jan Verkade
Principal Investigator Email
h.j.verkade@umcg.nl
Contact Person Name
Hendrik Jan Verkade
Contact Person Email
h.j.verkade@umcg.nl
Site Name
Wilhelmina Childrens Hospital
Department Name
Paediatric Gastroenterology
Principal Investigator Name
Wendy Van der Woerd
Principal Investigator Email
wwoerd@umcutrecht.nl
Contact Person Name
Wendy Van der Woerd
Contact Person Email
wwoerd@umcutrecht.nl

France

Earliest CTIS Part Ii Submission Date
19-01-2024
Latest Decision Or Authorization Date
13-08-2025
Processing Time Days
572
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Centre d'lnvestigation Clinique pediatrique
Principal Investigator Name
Madeleine AUMAR
Principal Investigator Email
madeleine.aumar@chu-lille.fr
Contact Person Name
Madeleine AUMAR
Contact Person Email
madeleine.aumar@chu-lille.fr
Site Name
Hopital Necker Enfants Malades
Department Name
Centre d'lnvestigation Clinique
Principal Investigator Name
Florence LACAILLE
Principal Investigator Email
florence.lacaille@aphp.fr
Contact Person Name
Florence LACAILLE
Contact Person Email
florence.lacaille@aphp.fr

Germany

Earliest CTIS Part Ii Submission Date
19-01-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
756
Number Of Sites
3
Number Of Participants
8

Sites

Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Klinik für Kinder- und Jugendmedizin, Gastroenterologie und Hepatologie
Principal Investigator Name
Ekkehard Sturm
Principal Investigator Email
Ekkehard.sturm@med.uni-tuebingen.de
Contact Person Name
Ekkehard Sturm
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für Paediatrie mit Schwerpunkt Gastroenterologie, Nephrologie und Stoffwechselmedizin
Principal Investigator Name
Philip Bufler
Principal Investigator Email
Philip.bufler@charite.de
Contact Person Name
Philip Bufler
Contact Person Email
Philip.bufler@charite.de
Site Name
Medizinische Hochschule Hannover
Department Name
Paediatrische Gastroenterologie, Hepatologie und Lebertransplantation
Principal Investigator Name
Ulrich Baumann
Principal Investigator Email
Baumann.U@mh-hannover.de
Contact Person Name
Ulrich Baumann
Contact Person Email
Baumann.U@mh-hannover.de

Poland

Earliest CTIS Part Ii Submission Date
19-01-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
756
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
Instytut Pomnik Centrum Zdrowia Dziecka
Department Name
Poradnia Chorob i Transplantacji Watroby
Principal Investigator Name
Piotr Czubkowski
Principal Investigator Email
p.czubkowski@ipczd.pl
Contact Person Name
Piotr Czubkowski
Contact Person Email
p.czubkowski@ipczd.pl

Italy

Earliest CTIS Part Ii Submission Date
19-01-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
756
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
Bambino Gesu Childrens Hospital
Department Name
Division of Hepatology, Gastroenterology and Nutrition
Principal Investigator Name
Andrea Pietrobattista
Principal Investigator Email
andrea.pietrobattista@opbg.net
Contact Person Name
Andrea Pietrobattista
Contact Person Email
andrea.pietrobattista@opbg.net
Site Name
Azienda Ospedaliera Universitaria Meyer IRCCS
Department Name
Epatologia
Principal Investigator Name
Giuseppe Indolfi
Principal Investigator Email
giuseppe.indolfi@meyer.it
Contact Person Name
Giuseppe Indolfi
Contact Person Email
giuseppe.indolfi@meyer.it
Site Name
Azienda Ospedale-Universita Padova
Department Name
Dipartimento Di Salute Della Donna E Del Bambino
Principal Investigator Name
Mara Cananzi
Principal Investigator Email
mara.cananzi@aopd.veneto.it
Contact Person Name
Mara Cananzi
Contact Person Email
mara.cananzi@aopd.veneto.it

Sponsor

Primary sponsor

Full Name
Ipsen Pharma
Organisation Type
Pharmaceutical company
Country Of Registered Address
France

Contract research organisations

Name
Syneos Health Netherlands B.V.
Responsibilities
Vendor Management, Clinical Site Monitoring and Site Management, Pharmacovigilance (Safety Management), Project and Site Start-up Services, DSMB Management, IAC Management, Investigator Payments, Project and Site Close-out Services
Name
PPD Global Limited
Responsibilities
sponsorDuties codes: [8] (as listed); contact yavor.angelski@ppd.com
Name
Almac Clinical Services Limited
Responsibilities
sponsorDuties codes: [14]; contact info@almacgroup.com
Name
Almac Clinical Technologies LLC
Responsibilities
sponsorDuties codes: [3]; contact info@almacgroup.com

Third parties

  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]; contact helpdesk@mdsol.com","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties codes: [4]; contact siteservices.eu@ppd.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties codes: [14]; contact info@almacgroup.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"PPD Global Limited","duties_or_roles":"sponsorDuties codes: [8]; contact yavor.angelski@ppd.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"sponsorDuties codes: [15]; value: \"Patient Travel Reimbursement\"; contact support@greenphire.com","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties codes: [3]; contact info@almacgroup.com","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"sponsorDuties codes: [1,12,13,15,5,6,8,9]; value: \"Vendor Management, Clinical Site Monitoring and Site Management, Pharmacovigilance (Safety Management), Project and Site Start-up Services, DSMB Management, IAC Management, Investigator Payments, Project and Site Close-out Services\"; contact sm_clinopsams@syneoshealth.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: [15]; value: \"electronic clinical outcome assessment (\\\"eCOA\\\") Services\"; contact customercare@clario.com","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
KAYFANDA 200 microgram hard capsules
Active Substance
odevixibat
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Marketing authorisation (EU) EU/1/24/1854/001
Dose Levels
200 microgram hard capsule
Frequency
Daily
Maximum Dose
120 µg/Kg per day
Investigational Product Name
KAYFANDA 400 microgram hard capsules
Active Substance
odevixibat
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Marketing authorisation (EU) EU/1/24/1854/002
Dose Levels
400 microgram hard capsule
Frequency
Daily
Maximum Dose
120 µg/Kg per day
Investigational Product Name
KAYFANDA 600 microgram hard capsules
Active Substance
odevixibat
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Marketing authorisation (EU) EU/1/24/1854/003
Dose Levels
600 microgram hard capsule
Frequency
Daily
Maximum Dose
120 µg/Kg per day
Investigational Product Name
KAYFANDA 1 200 microgram hard capsules
Active Substance
odevixibat
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Marketing authorisation (EU) EU/1/24/1854/004
Dose Levels
1200 microgram hard capsule
Frequency
Daily
Maximum Dose
120 µg/Kg per day

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