Clinical trial NCT03217422: ADCC Mediated B-Cell dEpletion and BAFF-R Blockade
Official title: A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of VAY736 in Autoimmune Hepatitis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Autoimmune Hepatitis
Keywords: Type 1
Type 2
autoimmune hepatitis
AIH
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-07-14
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: VAY736 dose testing; VAY736 efficacy and safety testing.

Detailed description: This is a randomized, placebo-controlled, double-blind dose range study in autoimmune hepatitis. The study population consists of female and male adult autoimmune hepatitis patients with incomplete response or intolerant to standard treatment of care. The diagnosis of autoimmune hepatitis has to fulfill the IAIHG criteria and must be confirmed by liver histology.

Patients will be randomly assigned to different doses of VAY736 or placebo. The primary analysis is planned at 24 weeks. A subsequent study part will then test the efficacy and safety of VAY736 in a parallel group design. For this part of the trial a new group of autoimmune hepatitis patients will be enrolled.

Eligibility criteria: Key Inclusion Criteria:

1. AIH diagnosed per International Autoimmune Hepatitis Group
2. Liver biopsy with Ishak modified HAI indicating active AIH
3. Incomplete response to OR intolerance of standard therapy (per AASLD)

Key Exclusion Criteria

1. Prior use of any B-cell depleting therapy (e.g., rituximab or other anti-CD20 mAb, anti-CD22 mAb or anti-CD52 mAb) within 1 year prior to Screening or as long as B-cell count \<50 cells/µL
2. Required regular use of medications with known hepatotoxicity
3. Decompensated cirrhosis
4. Diagnosis of overlap syndrome with AIH (e.g., AIH+PBC, AIH+PSC).
5. Drug related AIH at screening or a history of drug related AIH.
6. History of drug abuse or unhealthy alcohol use
7. History of malignancy of any organ system
8. Pregnant or nursing (lactating) women

Primary outcomes:
measure: ALT (Alanine aminotransferase) normalization
timeFrame: Week 24
Secondary outcomes:
measure: ALT normalization by dose
timeFrame: Week 24
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Houston
country: United States
facility: St. Lukes Advanced Liver Therapies
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Vinohrady
country: Czechia
facility: Novartis Investigative Site
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Takamatsu city
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Itabashi ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Chung YY, Rahim MN, Heneghan MA. Autoimmune hepatitis and pregnancy: considerations for the clinician. Expert Rev Clin Immunol. 2022 Apr;18(4):325-333. doi: 10.1080/1744666X.2022.2044307. Epub 2022 Mar 2.