Efficacy and Safety of Odevixibat in Patients With Alagille Syndrome (ASSERT)

A Phase 3 Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of Odevixibat (A4250) in Patients With Alagille Syndrome (ASSERT)

Double-blind, randomized, placebo-controlled, Phase 3 study to investigate the efficacy and safety of odevixibat compared to placebo in Patients with Alagille Syndrome.

Study Overview

• Status: Completed
• Conditions: Alagille Syndrome
• Intervention / Treatment: Drug: Odevixibat; Drug: Placebo

Detailed Description

Approximately 35 sites will be initiated for this study in North America, Europe, Middle East, and Asia Pacific.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc Bruxelles
• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
• France
  • Bron, France, 69677
    • Hôpital Femme Mère Enfant de Lyon
  • Lille, France, 59037
    • Antenne pédiatrique du CIC - Hopital Jeanne De Flandre
  • Marseille, France, 13385
    • APHM
  • Paris, France, 75015
    • Hopital Necker Enfants Malades
• Germany
  • Berlin, Germany, 13353
    • Charite-Universitatsmedizin Berlin
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Tübingen, Germany, 72076
    • Universitatsklinik fur Kinder-und Jugendmedizin Tubingen
• Israel
  • Jerusalem, Israel, 9103102
    • Sharie Zedek
  • Petah tikva, Israel, 4920235
    • Schneider Children's Medical Center of Israel
• Italy
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII
  • Firenze, Italy, 50139
    • AOU Meyer
  • Padova, Italy, 35128
    • Azienda Ospedale Università Padova
  • Rome, Italy, 00165
    • Bambino Gesù Children's Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University of Malaya Medical Centre
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen (Umcg)
  • Utrecht, Netherlands, 3584EA
    • University Medical Centre Utrecht, WKZ
• New Zealand
  • Auckland, New Zealand, 1023
    • Starship Child Health
• Poland
  • Warszawa, Poland, 04-730
    • Instytut Pomnik-Centrum Zdrowia Dziecka
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe Üniversitesi İhsan Doğramacı Çocuk Hastanesi
  • Fatih, Turkey, 34093
    • Istanbul University Medical Faculty Hospital
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California - San Francisco
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital and Clinics
  • New York
    • Bronx, New York, United States, 10467
      • The Childrens Hospital at Montefiore Albert Einstein School of Medicine
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University School of Medicine
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Genetically confirmed diagnosis of Alagille syndrome
• History of significant pruritus as measured by the Albireo Observer or Patient Reported Outcome instrument
• Elevated serum bile acid level

Key Exclusion Criteria:

• History or ongoing presence of other types of liver disease (eg. biliary atresia, progressive familial intrahepatic cholestasis, hepatocellular carcinoma)
• History of liver transplant, or a liver transplant is planned within 6 months of randomization
• ALT >10× upper limit of normal (ULN) at screening
• Total bilirubin >15 × ULN at screening
• Patient suffers from uncontrolled, recalcitrant pruritic condition other than Alagille syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Odevixibat (A4250); Capsules for oral administration once daily for 24 weeks.	Drug: Odevixibat; Odevixibat is a small molecule and selective inhibitor of IBAT.; Other Names: A4250
Placebo Comparator: Placebo; Capsules for oral administration (to match active) once daily for 24 weeks.	Drug: Placebo; Placebo identical in appearance to experimental drug (odevixibat).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Scratching Score	Change from baseline in average AM (measured after waking up) and PM (measured before bedtime) scratching score to Month 6 as measured by the Albireo Observer-Reported Outcome (ObsRO) Instrument. The ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with scores from 0 to 4 where 0 is no scratching and 4 is worst possible scratching.	Change from baseline for each four-week average pruritis score to Month 6 (Weeks 21 to 24), in which baseline was calculated based on the 14 days before the start of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Bile Acid Levels	Change in serum bile acid levels (μmol/L) from baseline to average of week 20 and 24	Change from baseline to average of week 20 and 24, where baseline was calculated by averaging the last two values preceding start of treatment, and average of Week 20 and Week 24 was defined as the average of Week 20 and Week 24 values.

Collaborators and Investigators

• Sponsor: Albireo

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Actual): September 9, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 19, 2020

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: ALGS; Alagille syndrome
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Disease; Congenital Abnormalities; Liver Diseases; Genetic Diseases, Inborn; Biliary Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Abnormalities, Multiple; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Syndrome; Alagille Syndrome
• Other Study ID Numbers: A4250-012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No