Efficacy and Safety of Odevixibat in Patients With Alagille Syndrome

NCT04674761 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: A4250-012
• Study Type: interventional
• Target: 52
• Locations: 13 countries
• Sites: 32

Brief Summary

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

Conditions

Alagille Syndrome

Keywords

ALGS; Alagille syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Serum Bile Acid Levels

  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.

Study Arms (2)

Odevixibat (A4250)

EXPERIMENTAL

Capsules for oral administration once daily for 24 weeks.

Drug: Odevixibat

Placebo

PLACEBO COMPARATOR

Capsules for oral administration (to match active) once daily for 24 weeks.

Drug: Placebo

Interventions

Odevixibat DRUG

Odevixibat is a small molecule and selective inhibitor of IBAT.

Also known as: A4250

Odevixibat (A4250)

Placebo DRUG

Placebo identical in appearance to experimental drug (odevixibat).

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Albireo: lead

Study Sites (32)

University of California - San Francisco

San Francisco, California, 94158, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Mercy Hospital and Clinics

Kansas City, Missouri, 64108, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

The Childrens Hospital at Montefiore Albert Einstein School of Medicine

The Bronx, New York, 10467, United States

Location

Oregon Health Science University School of Medicine

Portland, Oregon, 97239, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Cliniques Universitaires Saint-Luc Bruxelles

Brussels, 1200, Belgium

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Hôpital Femme Mère Enfant de Lyon

Bron, 69677, France

Location

Antenne pédiatrique du CIC - Hopital Jeanne De Flandre

Lille, 59037, France

Location

APHM

Marseille, 13385, France

Location

Hopital Necker Enfants Malades

Paris, 75015, France

Location

Charité-Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinik für Kinder-und Jugendmedizin Tübingen

Tübingen, 72076, Germany

Location

Sharie Zedek

Jerusalem, 9103102, Israel

Location

Schneider Children's Medical Center of Israel

Petah Tikva, 4920235, Israel

Location

ASST Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

AOU Meyer

Florence, 50139, Italy

Location

Azienda Ospedale Università Padova

Padua, 35128, Italy

Location

Bambino Gesù Children's Hospital

Rome, 00165, Italy

Location

University of Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Universitair Medisch Centrum Groningen (UMCG)

Groningen, 9713 GZ, Netherlands

Location

University Medical Centre Utrecht, WKZ

Utrecht, 3584EA, Netherlands

Location

Starship Child Health

Auckland, 1023, New Zealand

Location

Instytut Pomnik-Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Hacettepe Üniversitesi İhsan Doğramacı Çocuk Hastanesi

Ankara, 06230, Turkey (Türkiye)

Location

Istanbul University Medical Faculty Hospital

Fatih, 34093, Turkey (Türkiye)

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Ovchinsky N, Aumar M, Baker A, Baumann U, Bufler P, Cananzi M, Czubkowski P, Durmaz O, Fischer R, Indolfi G, Karnsakul WW, Lacaille F, Lee WS, Maggiore G, Rosenthal P, Ruiz M, Sokal E, Sturm E, van der Woerd W, Verkade HJ, Wehrman A, Clemson C, Yu Q, Ni Q, Ruvido J, Manganaro S, Mattsson JP. Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSERT): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2024 Jul;9(7):632-645. doi: 10.1016/S2468-1253(24)00074-8. Epub 2024 Apr 23.

  PMID: 38670135 DERIVED

MeSH Terms

Conditions

Alagille Syndrome

Interventions

odevixibat

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Results Point of Contact

• Title: Albireo AB
• Organization: Albireo AB

medinfo@albireopharma.com

medinfo@albireopharma.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: December 19, 2020
• Study Start: March 19, 2021
• Primary Completion: September 9, 2022
• Study Completion: September 9, 2022
• Last Updated: November 2, 2023
• Results First Posted: November 2, 2023

Record last verified: 2023-10

Locations

CA (1); PL (1); FR (4); IL (2); NL (2); NZ (1); TU (2); MY (1); GB (1); DE (3); IT (4); BE (1); US (9)