Study of ARC-520 in Participants With Hepatitis B Virus e Antigen (HBeAg) Positive Chronic Hepatitis B Virus

Arrowhead Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: diphenhydramine; Drug: Entecavir; Drug: ARC-520; Drug: Placebo; Drug: Tenofovir

Study type: Interventional

Funder types: Industry

Identifiers

NCT02452528

Heparc-2004

Details and patient eligibility

About

Participants with chronic HBV infection will receive multiple doses of ARC-520 in combination with entecavir or tenofovir and be evaluated for safety and efficacy.

Enrollment: 4 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female, 18 to 75 years of age
• Written informed consent
• Body mass index (BMI) between 17.5 and 30.0 kg/m2
• No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment
• No abnormal finding of clinical relevance
• Diagnosis of HBeAg positive, immune active, chronic HBV infection
• > 2 months of continuous treatment with daily oral entecavir or tenofovir
• Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive)

Exclusion criteria

• Pregnant or lactating
• Acute signs of hepatitis/other infection within 4 weeks of screening
• Hepatic transaminases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) > 3 times the upper limits of normal
• Liver Elastography (i.e. FibroScan®) score > 9
• Antiviral therapy other than entecavir or tenofovir within 3 months of screening
• Prior treatment with interferon in the last 3 years
• Use of anticoagulants, corticosteroids, immunomodulators, or immunosuppressants within 6 months of screening
• Use within 7 days prior to screening of dietary and/or herbal supplements that can interfere with liver metabolism
• Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days of study drug administration
• Use of prescription medication within 14 days prior to study drug administration
• Depot injection/implant of any drug except birth control within 3 months prior to study drug administration
• Known diagnosis of diabetes mellitus
• History of autoimmune disease
• Human immunodeficiency virus (HIV) infection
• Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis
• Hypertension; blood pressure > 150/100 mmHg
• 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, in situ cervical cancer
• Major surgery within 3 months of screening
• History of alcohol and/or drug abuse < 12 months from screening
• Regular use of alcohol within 6 months (ie, more than 14 units of alcohol per week)
• Evidence of systemic acute inflammation, sepsis, or hemolysis
• Diagnosed with a significant psychiatric disorder
• Use of drugs of abuse
• History of allergy to bee venom
• Positive reaction to the bee venom allergy immunoglobulin E (IgE) test
• Use of investigational agents or devices within 30 days
• Clinically significant inherited or acquired gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease
• Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction
• Clinically significant history or presence of uncontrolled systemic disease
• Donated or had a loss of whole blood of 50 milliliters (mL) to 499 mL within 30 days or more than 499 mL between 31 and 56 days prior to study treatment
• History of fever within 2 weeks of screening
• Immunization/planned immunization with live attenuated vaccine except influenza vaccine
• Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk
• Excessive exercise/physical activity within 7 days of screening/enrolment or during study
• History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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4 participants in 2 patient groups, including a placebo group

ARC-520

Experimental group

Description:

Intravenous administration of 1.0 mg/kg ARC-520 once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study. Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of study drug.

Treatment:

Drug: Tenofovir

Drug: ARC-520

Drug: Entecavir

Drug: diphenhydramine

Placebo

Placebo Comparator group

Description:

Intravenous administration of normal saline (0.9%) once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study. Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of placebo.

Treatment:

Drug: Tenofovir

Drug: Entecavir

Drug: Placebo

Drug: diphenhydramine