Study of ARC-520 With or Without Other Drugs Used in the Treatment of Chronic Chronic Hepatitis B Virus (HBV) (MONARCH)
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
Patients with chronic HBV infection will receive either ARC-520 alone or ARC-520 in combination with other treatments such as entecavir (ENT) or tenofovir (TDF) and/or pegylated interferon (PEG IFN) alpha 2a therapy, and be evaluated for safety and efficacy.
Full description
This is a multicenter, open-label study of ARC-520 based treatment regimens administered to patients with HBeAg positive or HBeAg negative immune active chronic Hepatitis B Virus (HBV) infection of various genotypes, or patients with Hepatitis D Virus (HDV). Eligible patients naive to previous treatment, and who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 alone or ARC-520 plus additional treatments such as entecavir (ETV) or tenofovir (TDF) and/or pegylated interferon alpha 2a (PEG IFN) therapy. The study may initially involve up to a total of 96 eligible chronic HBV and HDV infected patients. Patients in all cohorts will receive a total of 13 doses of ARC-520 at 2mg/kg or 4 mg/kg. Patients will undergo the following evaluations at regular intervals during the study: medical history, physical examinations, vital sign measurements (blood pressure, heart rate, respiratory rate, and temperature), weight, adverse events assessment (AEs), 12-lead ECGs, liver fibrosis testing, concomitant medication assessment, blood sample collection for hematology, coagulation, chemistry, exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, cytokines, Follicle Stimulating Hormone (FSH) testing (post-menopausal females) and pregnancy testing for females of childbearing potential. Clinically significant changes including AEs will be followed until resolution, until the condition stabilizes, until the event is otherwise explained, or until the patient is lost to follow-up. For each patient, the duration of the study is approximately 96 weeks, from enrolment to last visit. Prior to enrolment there is a 60 day screening period. Addition of new cohorts and additional treatment regimens are anticipated for this study.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- Male or female, 18 to 75 years of age
- Written informed consent
- No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment
- Diagnosis of HBeAg negative or positive chronic HBV infection.
- Must be HBsAg (+) during screening.
- Must be treatment naïve: never on PEG IFN alpha 2a and/or ETV or TDF; and
- Have not used nucleoside/nucleotide analogs (NUCs) within the last 2 years prior to dosing on Day 1
- Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners)
Exclusion criteria
- Pregnant or lactating
- Acute signs of hepatitis/other severe infections within 4 weeks of screening
- Use within the last 14 days or anticipated requirement for anticoagulants, systemic corticosteroids, immunomodulators, or immunosuppressants
- Use of prescription medication within 14 days prior to treatment administration except: topical products without systemic absorption, statins (except rosuvastatin), hypertension medications, over-the-counter (OTC) and prescription pain medication or hormonal contraceptives
- History of poorly controlled autoimmune disease or any history of autoimmune hepatitis
- History of heterozygous or homozygous familial hypercholesterolemia.
- Human immunodeficiency virus (HIV) infection
- Is sero-positive for Hepatitis C Virus (HCV), or has a history of delta virus hepatitis (except for cohort in which delta virus infection is acceptable)
- Has hypertension: blood pressure > 170/100 mmHg; well-controlled blood pressure on hypertensive medication allowed
- History of cardiac rhythm disturbances
- Family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death
- Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease within 6 months prior to study entry
- History of malignancy, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer
- Has had major surgery within 1 month of screening
- Regular use of alcohol within 6 months prior to screening (ie, more than 14 units of alcohol per week)
- Use of recreational drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year prior to the screening
- History of allergy to bee sting
- Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's disease, hemochromatosis, or alpha-1 antitrypsin deficiency
- Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction
- Clinically significant history or presence of poorly controlled/uncontrolled systemic disease
- Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk
- History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s)
Trial design
Primary purpose
Allocation
Interventional model
Masking
79 participants in 8 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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