Effect of RO7049665 on the Time to Relapse Following Steroid Tapering in Participants With Autoimmune Hepatitis (AIH)

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the effect of RO7049665 on time to relapse following forced corticosteroid (CCS) tapering as measured by the hazard ratio between RO7049665 7.5 milligrams (mg) and placebo arm.

Official Title
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A Double-Blind, Randomized, Parallel-Group, Phase 2 Study to Investigate the Effect of RO7049665 on the Time to Relapse Following Steroid Tapering in Patients With Autoimmune Hepatitis

Conditions
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Autoimmune Hepatitis, Autoimmune Chronic Hepatitis

Intervention / Treatment
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* Drug: RO7049665
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with a definite diagnosis of AIH (type 1, 2 and 3) as per simplified or revised original diagnostic criteria Participants who have been in biochemical remission for > 2 years (or less if according to the local practice) prior to randomization Participants who have been on stable treatment (corticosteroids [CCSs] +/- non-specific immunosuppressants [NSIs]) for at least 3 months prior to randomization and who have not had a dose increase in the previous 6 months prior to randomization No signs of liver inflammation on a liver biopsy taken no more than 12 months prior to randomization Participants with AIH who have previously not attempted (or not attempted in the last 3 years, if this is the local practice) to taper CCSs to 0 mg/day Body mass index within the range of 18-35 kilograms per meter square (kg/m^2) Women of childbearing potential who agree to remain abstinent or use at least one acceptable contraceptive method during the treatment period and for at least 28 days after the final dose of study drug Exclusion Criteria: Participants with cirrhosis (F4 fibrosis by Fibroscan®) with significant impairment of liver function (Child Pugh category B or C) Any other autoimmune disease requiring immunomodulating treatment History of infection with hepatitis B, human immunodeficiency virus, active hepatitis C virus (HCV) infection, detection of replicating cytomegalovirus (CMV) or Epstein-Barr virus (EBV) Active infections requiring systemic therapy with antibiotic, antiviral, or antifungal treatment or febrile illness within 7 days before Day-1 History of primary or acquired immunodeficiency Pregnant or lactating female participants Symptomatic herpes zoster within 3 months prior to screening History of active or latent tuberculosis or a positive Quantiferon Gold test History of clinically significant severe drug allergies, multiple drug allergies, allergy to any constituent of the product, or intolerance to topical steroids Lymphoma, leukemia, or any malignancy within the past 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years and in situ carcinoma of the cervix that was completely removed surgically. Breast cancer within the past 10 years Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders Any condition or disease detected during the medical interview/physical examination that would render the participant unsuitable for the study, place the participant at undue risk, or interfere with the ability of the participant to complete the study in the opinion of the Investigator CCSs of <5 mg/day, or <2.5 mg CCSs plus immune suppressant, or <3 mg/day budesonide with or without immune suppressant CCSs >20 mg/day or >9 mg/day budesonide Non-specific immunosuppressant (NSI) daily dose higher than recommended standard of care therapy T or B cell-depleting therapy within the last 12 months or T- or B-cell number below normal due to depleting therapy Leukocyte apheresis within 12 weeks of screening Donation of blood or blood products in excess of 500 milliliters (mL) within 3 months prior to screening. Exposure to any investigational treatment within 6 months prior to Day 1 Abnormal hematologic, hepatic enzyme, hepatic function, or biochemistry values

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: RO7049665 3.5 mg<br>Participants will receive RO7049665 3.5 mg, administered as subcutaneous (SC) injection, every 2 weeks (Q2W) until participants experience relapse or the study is closed. | Drug: RO7049665<br>* RO7049665, subcutaneous injection, Q2W.<br>|
| Experimental: RO7049665 7.5 mg<br>Participants will receive RO7049665 7.5 mg, administered as SC injection, Q2W until participants experience relapse or the study is closed. | Drug: RO7049665<br>* RO7049665, subcutaneous injection, Q2W.<br>|
| Placebo Comparator: Placebo<br>Participants will receive RO7049665-matching placebo, administered as SC injection, Q2W until participants experience relapse or the study is closed. | Other: Placebo<br>* RO7049665-matching placebo, subcutaneous injection, Q2W.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Relapse for RO7049665 7.5 mg Versus Placebo | The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | From randomization (Day 1) up to relapse or end of the study (up to approximately 25 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Alanine Aminotransferase (ALT) | The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Up to end of the study (up to approximately 25 months) | 
| Change From Baseline in Aspartate Aminotransferase (AST) | The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Up to end of the study (up to approximately 25 months) | 
| Change From Baseline in Immunoglobulin G (IgG) | The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Up to end of the study (up to approximately 25 months) | 
| Time to Relapse for RO7049665 3.5 mg Versus Placebo | The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | From Randomization (Day 1) up to relapse or end of the study (up to approximately 25 months) | 
| Percentage of Participants With Adverse Events (AEs) | The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Up to end of the study (up to approximately 25 months) | 
| Number of Participants With Anti-drug Antibody (ADA) Emergence and Neutralizing Potential | The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Up to end of the study (up to approximately 25 months) |