Clinical trial NCT02452528: Study of ARC-520 in Participants With Hepatitis B Virus e Antigen (HBeAg) Positive Chronic Hepatitis B Virus
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Multi-dose Study to Determine the Depth of Hepatitis B Surface Antigen (HBsAg) Reduction Following Intravenous ARC-520 in Combination With Entecavir or Tenofovir in Patients With HBeAg Positive, Chronic Hepatitis B Virus (HBV) Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Hepatitis B Virus
Chronic Hepatitis B
HBV
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-05-22
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 85
timeFrame: Baseline, Day 85
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to Adverse Events (AEs)
timeFrame: From time of informed consent through Day 147 ± 3 days
measure: Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)
timeFrame: Through 48 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast)
timeFrame: Through 48 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)
timeFrame: Through 48 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Through 48 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of ARC-520: Apparent Clearance (CL)
timeFrame: Through 48 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V)
timeFrame: Through 48 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel)
timeFrame: Through 48 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2)
timeFrame: Through 48 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of Entecavir or Tenofovir: AUC0-24
timeFrame: Through 24 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of Entecavir or Tenofovir: AUClast
timeFrame: Through 24 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of Entecavir or Tenofovir: Cmax
timeFrame: Through 24 hours post-dosing on Days 1 and 57
measure: Pharmacokinetics of Entecavir or Tenofovir: Time of Cmax (Tmax)
timeFrame: Through 24 hours post-dosing on Days 1 and 57
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: Miami
country: United States
facility: Univ. Of Miami School Of Medicine/Center For Liver Diseases
state: Florida
city: New York
country: United States
facility: Ichan School of Medicine at Mount Sinai
state: New York
city: San Antonio
country: United States
facility: The Texas Liver Institute
state: Texas
Study officials:
References: