ADCC Mediated B-Cell dEpletion and BAFF-R Blockade

Study Overview
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Brief Summary
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VAY736 dose testing; VAY736 efficacy and safety testing.

Detailed Description
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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.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of VAY736 in Autoimmune Hepatitis

Conditions
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Autoimmune Hepatitis

Intervention / Treatment
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* Biological: VAY736
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: AIH diagnosed per International Autoimmune Hepatitis Group Liver biopsy with Ishak modified HAI indicating active AIH Incomplete response to OR intolerance of standard therapy (per AASLD) Key Exclusion Criteria 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 Required regular use of medications with known hepatotoxicity Decompensated cirrhosis Diagnosis of overlap syndrome with AIH (e.g., AIH+PBC, AIH+PSC). Drug related AIH at screening or a history of drug related AIH. History of drug abuse or unhealthy alcohol use History of malignancy of any organ system Pregnant or nursing (lactating) women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>VAY736 Dose 1 | Biological: VAY736<br>* VAY736<br>|
| Experimental: Arm 2<br>VAY736 Dose 2 | Biological: VAY736<br>* VAY736<br>|
| Experimental: Arm 3<br>VAY736 Dose 3 | Biological: VAY736<br>* VAY736<br>|
| Placebo Comparator: Arm 4<br>Placebo | Other: Placebo<br>* Placebo control with conversion to active VAY736<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALT (Alanine aminotransferase) normalization | Difference in ALT normalization | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALT normalization by dose | VAY736 dose-response | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1, Type 2, autoimmune hepatitis, AIH