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

Phase 2
Terminated
Conditions
Autoimmune Hepatitis
Autoimmune Chronic Hepatitis
Interventions
Other: Placebo
Registration Number
NCT04790916
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
2
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants will receive RO7049665-matching placebo, administered as SC injection, Q2W until participants experience relapse or the study is closed.
RO7049665 3.5 mgRO7049665Participants will receive RO7049665 3.5 mg, administered as subcutaneous (SC) injection, every 2 weeks (Q2W) until participants experience relapse or the study is closed.
RO7049665 7.5 mgRO7049665Participants will receive RO7049665 7.5 mg, administered as SC injection, Q2W until participants experience relapse or the study is closed.
Primary Outcome Measures
NameTimeMethod
Time to Relapse for RO7049665 7.5 mg Versus PlaceboFrom randomization (Day 1) up to relapse or end of the study (up to approximately 25 months)

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Immunoglobulin G (IgG)Up to end of the study (up to approximately 25 months)

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.

Time to Relapse for RO7049665 3.5 mg Versus PlaceboFrom Randomization (Day 1) up to relapse or end of the study (up to approximately 25 months)

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.

Change From Baseline in Alanine Aminotransferase (ALT)Up to end of the study (up to approximately 25 months)

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.

Change From Baseline in Aspartate Aminotransferase (AST)Up to end of the study (up to approximately 25 months)

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.

Percentage of Participants With Adverse Events (AEs)Up to end of the study (up to approximately 25 months)

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.

Number of Participants With Anti-drug Antibody (ADA) Emergence and Neutralizing PotentialUp to end of the study (up to approximately 25 months)

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.

Trial Locations

Locations (14)

The Alfred Hospital - Professor Stuart Roberts' Clinic - The Alfred Centre Location

🇦🇺

Melbourne, Victoria, Australia

Toronto General Hospital

🇨🇦

Toronto, Ontario, Canada

Martin Zeitz Centrum für Seltene Erkrankungen ZSE Hamburg

🇩🇪

Hamburg, Germany

Universite de Montreal - Centre Hospitalier de l'Universite de Montreal CHUM - Hopital Saint-Luc

🇨🇦

Montreal, Quebec, Canada

Centro Hospitalar de Vila Real

🇵🇹

Vila Real, Portugal

Ospedale San Gerardo

🇮🇹

Monza, Lombardia, Italy

Nottingham University Hospitals NHS Trust - City Hospital

🇬🇧

Nottingham, United Kingdom

IRCCS Saverio De Bellis; Anatomia Patologica

🇮🇹

Castellana Grotte, Puglia, Italy

Pusan National University Hospital; division of pulmonology

🇰🇷

Busan, Korea, Republic of

University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Liver Center

🇰🇷

Seoul, Korea, Republic of

Amsterdam UMC - location AMC

🇳🇱

Amstermdam, Netherlands

Radboud Universiteit - Radboud Universitair Medisch Centrum Radboudumc

🇳🇱

Nijmegen, Netherlands

Korea University Ansan Hospital

🇰🇷

Gyeonggi-do, Korea, Republic of

King College Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

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