Chronic Hepatitis B Virus Infection MedDRA version: 19.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Arrowhead Research Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for randomization, the following criteria must be met: 1. Male or female, 18 to 75 years of age, inclusive, at the time of informed consent. 2. Able to provide written informed consent prior to the performance of any study specific procedures. 3. Body mass index (BMI) between 17.5 and 30.0 kg/m2, inclusive. BMI = weight (kg)/(height [m])2 4. Have no abnormalities at screening or pre-dose 12-lead ECG assessment (measured after the patient is supine for at least 3 minutes) that, in the opinion of the principal investigator, may compromise patient’s safety in this study. 5. Willing and able to comply with all study assessments and adhere to the protocol schedule. 6. Have suitable venous access for blood sampling. 7. Have no new abnormal finding of clinical relevance at the screening evaluation. 8. Have a diagnosis of HBeAg positive, immune active, chronic HBV infection (HBsAg (+) for > 6 months) and all of the following: a. History of being HBsAg positive at 2 time points > 6 months apart, one of which can include at screening b. HBeAg positive at screening c. HBV DNA 2 months of continuous treatment with daily, oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) and a willingness to continue taking entecavir or tenofovir throughout the study. 10. Patients must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners) during the study and for 3 months following the last study treatment (ARC-520 or PBO). Males must not donate sperm for at least 3 months post-dose of the last study treatment. Male partners of female patients and female partners of male patients must also use contraception, if they are of childbearing potential. Females of childbearing potential must have a negative urine pregnancy test at screening and predose on Day 1. Females not of childbearing potential must be postmenopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle-stimulating hormone (FSH) level > 40 mIU/mL. Contraception that is deemed acceptable in this study includes the following: a. Condom b. Birth control pills (The Pill) c. Depot or injectable birth control (administered at least 3 months prior to planned study dose) d. Intrauterine device e. Birth Control Patch (eg, Ortho Evra®) f. NuvaRing® g. Surgical sterilization (ie, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women or vasectomy for men) Rhythm methods WILL NOT be considered as highly effective methods of contraception, however abstinence may be allowed based on opinion of treating physician. 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 39 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: A potential patient will be excluded from the study if any of the following criteria apply: 1. Female patients have a positive pregnancy test or are lactating. 2. Acute signs of hepatitis other severe infection (eg, moderate fever, jaundice, nausea, vomiting, and abdominal pain) evident within 4 weeks of screening and/or at the screening examination. 3. Hepatic transaminases (ALT or AST) > 3X upper limits of normal at screening. 4. Liver Elastography (i.e. FibroScan®) score > 9 at screening (if FibroScan® is not available, the following tests/criteria are acceptable: FibroTest/Fibrosure score > 0.59 n/a; Accoustic Radiation Force Impulse (ARFI, e.g Siemens Acuson) >1.55 m/s; Shear Wave Elastography (e.g. Aixplorer) >10.0 kPa at screening). 5. Patients with antiviral therapy other than entecavir or tenofovir within 3 months of screening or prior treatment with interferon in the last 3 years. 6. Use within the last 6 months or an anticipated requirement for anticoagulants, systemically administered corticosteroids, systemically administered immunomodulators, or systemically administered immunosuppressants. 7. Use of prescription medication within 14 days prior to administration of study treatment that in the opinion of the PI or the Sponsor would interfere with study conduct. Topical products without systemic absorption, statins (except rosuvastatin), hypertensive medications, OTC and prescription pain medication or hormonal contraceptives (females) are acceptable. 8. Has had a depot injection or implant of any drug within 3 months prior to administration of study treatment, with the exception of injectable/implantable birth control. 9. Has a known diagnosis of Non-alcoholic steatohepatitis or homozygous or heterozygous familial hypercholesterolemia. 10. Patients with any of the following laboratory abnormalities: a. Serum creatinine > 1.5 mg/dL (132.6 µmol/L) b. International normalized ratio (INR) > 1.25 × ULN c. Platelets 150/100 mmHg at screening confirmed by repeat. Patients with well-controlled blood pressure on hypertensive medication for > 2 months prior to study treatment administration will be allowed. 15. Patients with a history of torsades de pointes, ventricular rhythm disturbances (eg, ventricular tachycardia or fibrillation), pathologic sinus bradycardia (heart rate 450 msec for males and > 470 msec for females, following ECG tracings at screening. 18. Has experienced symptoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: To evaluate the depth of HBsAg decline in response to multiple doses of ARC-520 compared to PBO in patients with chronic HBV infection as a measure of drug activity;Secondary Objective: Secondary Objectives: • To determine the incidence and frequency of adverse events possibly or probably related to treatment as a measure of safety and tolerability of ARC-520 when coadministered with a fixed dose of entecavir or tenofovir in patients with chronic HBV infection • To evaluate multi-dose pharmacokinetics (PK) of ARC-520 in patients with chronic HBV infection when coadministered with a fixed dose of entecavir or tenofovir in a subset of patients ;Primary end point(s): Change from baseline to Day 113 in log qHBsAg will be evaluated by treatment and dose using a repeated measures mixed model.;Timepoint(s) of evaluation of this end point: Day 113 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A secondary analysis of change from baseline in log qHBsAg by visit will be evaluated by treatment and dose using an ANOVA model for each time point.;Timepoint(s) of evaluation of this end point: Each visit | — |
Countries
Germany, Hong Kong, Korea, Republic of
Contacts
Public ContactIlse-Maria Nolan
ICON Clinical Research
Outcome results
None listed