E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autoimmune Hepatitis (AIH) |
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E.1.1.1 | Medical condition in easily understood language |
AIH is a chronic disease in which your body's immune system attacks the liver and causes inflammation and liver damage |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003827 |
E.1.2 | Term | Autoimmune hepatitis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
AIH is a chronic disease in which your body's immune system attacks the liver and causes inflammation and liver damage |
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E.2.2 | Secondary objectives of the trial |
¿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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to relapse from randomization |
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E.5.1.1 | 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) |
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E.5.2 | 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
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E.5.2.1 | 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) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Korea, Republic of |
New Zealand |
Germany |
Italy |
Netherlands |
Portugal |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |