Clinical trial NCT04790916: Effect of RO7049665 on the Time to Relapse Following Steroid Tapering in Participants With Autoimmune Hepatitis (AIH)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Autoimmune Hepatitis
Autoimmune Chronic Hepatitis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-03-10
Enrollment: 2
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: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to Relapse for RO7049665 7.5 mg Versus Placebo
timeFrame: From randomization (Day 1) up to relapse or end of the study (up to approximately 25 months)
Secondary outcomes:
measure: Change From Baseline in Alanine Aminotransferase (ALT)
timeFrame: Up to end of the study (up to approximately 25 months)
measure: Change From Baseline in Aspartate Aminotransferase (AST)
timeFrame: Up to end of the study (up to approximately 25 months)
measure: Change From Baseline in Immunoglobulin G (IgG)
timeFrame: Up to end of the study (up to approximately 25 months)
measure: Time to Relapse for RO7049665 3.5 mg Versus Placebo
timeFrame: From Randomization (Day 1) up to relapse or end of the study (up to approximately 25 months)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to end of the study (up to approximately 25 months)
measure: Number of Participants With Anti-drug Antibody (ADA) Emergence and Neutralizing Potential
timeFrame: Up to end of the study (up to approximately 25 months)
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: The Alfred Hospital - Professor Stuart Roberts' Clinic - The Alfred Centre Location
state: Victoria
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Universite de Montreal - Centre Hospitalier de l'Universite de Montreal CHUM - Hopital Saint-Luc
state: Quebec
city: Hamburg
country: Germany
facility: Martin Zeitz Centrum für Seltene Erkrankungen ZSE Hamburg
city: Monza
country: Italy
facility: Ospedale San Gerardo
state: Lombardia
city: Castellana Grotte
country: Italy
facility: IRCCS Saverio De Bellis; Anatomia Patologica
state: Puglia
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital; division of pulmonology
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seoul
country: Korea, Republic of
facility: University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Liver Center
city: Amstermdam
country: Netherlands
facility: Amsterdam UMC - location AMC
city: Nijmegen
country: Netherlands
facility: Radboud Universiteit - Radboud Universitair Medisch Centrum Radboudumc
city: Vila Real
country: Portugal
facility: Centro Hospitalar de Vila Real
city: London
country: United Kingdom
facility: King College Hospital NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: