A Study to Investigate the Effect of RO7049665 on the Time to Relapse Following Steroid Tapering in Patients With Autoimmune Hepatitis

• Register: EUCTR
• Last refreshed on: 6 December 2021
• Main ID: EUCTR2020-003990-23-NL
• Date of registration: 22/02/2021
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study to Investigate the Effect of RO7049665 on the Time to Relapse Following Steroid Tapering in Patients With Autoimmune Hepatitis
• Scientific 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
• Date of first enrolment: 28/04/2021
• Target sample size: 84
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-003990-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Germany, Italy, Korea, Republic of, Netherlands, New Zealand, Portugal, United Kingdom

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Age
•Age between 18 to 75 years

Type of Participants and Disease Characteristics
•Patients with a definite diagnosis of AIH (type 1, 2 and 3) as per simplified or revised original diagnostic criteria
•Patients who have been in biochemical remission for > 2 years prior to randomization
•Patients who have been on stable treatment for at least 6 months prior to randomization
•No signs of liver inflammation on a liver biopsy taken no more than 12 months prior to randomization.
•Patients with AIH who have previously not attempted to taper CCS to 0 mg/day

Weight
•Body mass index within the range of 18-35 kg/m2 (inclusive)

Sex and Contraception/Barrier Requirements
•Women of childbearing potential, who: agree to remain abstinent or use at least one acceptable contraceptive methods during the treatment period and for at least 28 days after the final dose of study drug

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

Exclusion criteria:
Medical Conditions
•Patients 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 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
•Female patients: Pregnant or lactating
•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 patient unsuitable for the study, place the patient at undue risk, or interfere with the ability of the patient to complete the study in the opinion of the Investigator
Prior/Concomitant Therapy
•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
•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
Prior/Concurrent Clinical Study Experience
•Leukocyte apheresis within 12 weeks of screening.
•Donation of blood or blood products in excess of 500 mL within 3 months prior to screening.
•Exposure to any investigational treatment within 6 months prior to Day 1

Laboratory Abnormalities
•Abnormal hematologic, hepatic enzyme or hepatic function, biochemistry values

Other Exclusions
•History of regular alcohol consumption within 2 months of screening
•Any suspicion or history of illicit drug use
•Patients under judicial supervision, guardianship, or curatorship



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Autoimmune Hepatitis (AIH)
MedDRA version: 20.1 Level: PT Classification code 10003827 Term: Autoimmune hepatitis System Organ Class: 10019805 - Hepatobiliary disorders

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

Product Name: IgG IL2/RO7049665
Product Code: RO7049665
Pharmaceutical Form: Solution for injection
INN or Proposed INN: NA
CAS Number: 2056881-92-4
Current Sponsor code: RO7049665
Other descriptive name: RO7049665/IgG-IL2/ IgG-IL2ND2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: AIH is a chronic disease in which your body's immune system attacks the liver and causes inflammation and liver damage

Primary end point(s): Time to relapse from randomization

Secondary Objective: •To assess changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and IgG over time and by dose
•To evaluate the effect of RO7049665 on time to relapse following forced CCS tapering as measured by the hazard ratio between 3.5 mg RO7049665 and placebo
•To evaluate the safety and tolerability of RO7049665 in participants with AIH

Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed when the required number of events has occurred (Approximately 60 months)

Secondary Outcome(s)

Secondary end point(s): Efficacy
1.ALT, AST, and IgG (for both ?, absolute and relative [upper limit of normal]) over time
2.Time to relapse from randomization
3.Incidence and severity of adverse events
4.Changes in vital signs, physical examination, ECG parameters, and safety laboratory parameters
5.Anti-drug antibody emergence and neutralizing potential

Timepoint(s) of evaluation of this end point: 1-5. The secondary endpoints will be assessed when the required number of events has occurred (Approximately 60 months)

Secondary ID(s)

BP42698

Source(s) of Monetary Support

F. Hoffman-La Roche Ltd

Ethics review

Status: Approved
Approval date: 28/04/2021
Contact: