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

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

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.

Study Overview

• Status: Terminated
• Conditions: Autoimmune Hepatitis; Autoimmune Chronic Hepatitis
• Intervention / Treatment: Drug: RO7049665; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital - Professor Stuart Roberts' Clinic - The Alfred Centre Location
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Universite de Montreal - Centre Hospitalier de l'Universite de Montreal CHUM - Hopital Saint-Luc
• Germany
  • Hamburg, Germany, 20246
    • Martin Zeitz Centrum für Seltene Erkrankungen ZSE Hamburg
• Italy
  • Lombardia
    • Monza, Lombardia, Italy, 20900
      • Ospedale San Gerardo
  • Puglia
    • Castellana Grotte, Puglia, Italy, 70013
      • IRCCS Saverio De Bellis; Anatomia Patologica
• Korea, Republic of
  • Busan, Korea, Republic of
    • Pusan National University Hospital; division of pulmonology
  • Gyeonggi-do, Korea, Republic of, 15355
    • Korea University Ansan Hospital
  • Seoul, Korea, Republic of, KOR
    • University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Liver Center
• Netherlands
  • Amstermdam, Netherlands, 1105 AZ
    • Amsterdam UMC - Location AMC
  • Nijmegen, Netherlands, 6525 GA
    • Radboud Universiteit - Radboud Universitair Medisch Centrum Radboudumc
• Portugal
  • Vila Real, Portugal, 5000-508
    • Centro Hospitalar de Vila Real
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King College Hospital NHS Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust - City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7049665 3.5 mg; 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; RO7049665, subcutaneous injection, Q2W.
Experimental: RO7049665 7.5 mg; Participants will receive RO7049665 7.5 mg, administered as SC injection, Q2W until participants experience relapse or the study is closed.	Drug: RO7049665; RO7049665, subcutaneous injection, Q2W.
Placebo Comparator: Placebo; Participants will receive RO7049665-matching placebo, administered as SC injection, Q2W until participants experience relapse or the study is closed.	Other: Placebo; RO7049665-matching placebo, subcutaneous injection, Q2W.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Actual): November 18, 2021
• Study Completion (Actual): November 18, 2021

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis, Autoimmune
• Other Study ID Numbers: BP42698; 2020-003990-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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