autoimmune condition chronic inflammation
Conditions
Interventions
See section E4 of the ABR form
Sponsors
Covance
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria Participants are eligible to be included in the study only if all of the following criteria apply: Informed Consent 1. Able and willing to provide written informed consent and to comply with the study protocol according to International Conference on Harmonisation (ICH) and local regulations. Age 2. Between 18 to 75 years of age, inclusive, at the time of signing the informed consent. Type of Participants and Disease Characteristics 3. Patients with a definite diagnosis of AIH (type 1, 2 and 3) as per simplified or revised original diagnostic criteria (including response to CCSs) (Hennes et al 2008). 4. Patients who have been in biochemical remission (complete normalization of serum transaminases and IgG levels) for * 2 years prior to randomization. 5. Patients who have been on stable treatment (CCSs * NSIs) for at least 6 months prior to randomization. 6. No signs of liver inflammation (HAI * 3) on a liver biopsy taken no more than 12 months prior to randomization. 7. Patients with AIH who have previously not attempted to taper CCS to 0 mg/day. Weight 8. Body mass index within the range of 18-35 kg/m2 (inclusive). Sex and Contraception/Barrier Requirements 9. Male and female participants are eligible. The contraception and abstinence requirements are intended to prevent exposure of an embryo to the study treatment. Therefore, the reliability of sexual abstinence for female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure. A female participant is only eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Women of non-childbearing potential (WONCBP), OR Women of childbearing potential (WOCBP), who: Agree to remain abstinent (refrain from heterosexual intercourse) 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. The following are acceptable contraceptive methods: bilateral tubal occlusion/ ligation, male sexual partner who is sterilized, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices, male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide.
Exclusion criteria
Exclusion criteria: Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Patients with cirrhosis (F4 fibrosis by Fibroscan®) with significant impairment of liver function (Child Pugh category B or C). 2. Any other autoimmune disease (including overlap syndrome) requiring immunomodulating treatment. 3. History of infection with hepatitis B (hepatitis B surface antigen [HBsAg] positive and/or anti-HBc positive; HBV vaccinated patients are eligible), human immunodeficiency virus (HIV; positive HIV antibody test), active hepatitis C virus (HCV) infection (detectable HCV RNA), detection of replicating CMV or Epstein-Barr virus. 4. Active infections requiring systemic therapy with antibiotic, antiviral or antifungal treatment or febrile illness within 7 days before Day *1. 5. History of primary or acquired immunodeficiency. 6. Female patients: Pregnant or lactating. 7. Symptomatic herpes zoster within 3 months prior to screening. 8. History of active or latent tuberculosis or a positive Quantiferon* Gold test. 9. History of clinically significant severe drug allergies, multiple drug allergies, allergy to any constituent of the product, or intolerance to topical steroids. 10. 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. 11. Significant uncontrolled comorbidity, such as cardiac (e.g., moderate to severe heart failure New York Heart Association [NYHA] Class III/IV), pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders (excluding UC). 12. 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 13. CCSs of * 5 mg/day (prednisolone-equivalent dose), or 9 mg/day budesonide. 15. NSI daily dose higher than recommended standard of care therapy. 16. T or B cell-depleting therapy (e.g., rituximab) within the last 12 months or T- or B-cell number below normal due to depleting therapy. Prior/Concurrent Clinical Study Experience 17. Leukocyte apheresis within 12 weeks of screening. 18. Donation of blood or blood products in excess of 500 mL within 3 months prior to screening. 19. Exposure to any investigational treatment within 6 months prior to Day 1. Laboratory Abnormalities 20. Abnormal hematologic values: * Anemia (hemoglobin * 9 g/dL) * Leukocytosis (white blood cells * 2 * ULN) * Thrombocytopenia (platelet count * 100,000/*L) * Thrombocytosis (platelet count * 2 * ULN) * Eosinophilia (eosinophil count * 2 * ULN) 21. Abnormal hepatic enzyme or hepatic function values: * ALT, AST, or alkaline phosphatase, above normal range * Total bilirubin * 2 * ULN * International normalized rat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints - Time to relapse from randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints - ALT, AST, and IgG (for both absolute and relative [ULN]) over time. - Time to relapse from randomization. - Incidence and severity of adverse events. - Changes in vital signs, physical examination, ECG parameters, and safety laboratory parameters. - ADA emergence and neutralizing potential. | — |
Countries
Netherlands
Outcome results
None listed