Study of ARC-520 in Patient With Chronic Hepatitis B Virus
Primary Purpose
Chronic Hepatitis B
Status
Withdrawn
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
ARC-520 Injection
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Hepatitis B, HBV infection, Hepatitis B Surface Antigen
Eligibility Criteria
Inclusion Criteria:
- Male or female, 18 to 65 years of age
- Written informed consent
- No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment
- No abnormal finding of clinical relevance
- Diagnosis of immune active chronic HBV infection
- > 6 months of continuous treatment with daily, oral entecavir or tenofovir
Exclusion Criteria:
- Pregnant or lactating
- Acute signs of hepatitis/other infection within 4 weeks of screening
- Antiviral therapy other than entecavir or tenofovir within 3 months of screening
- Prior treatment with interferon or a toll receptor agonist in last 12 months
- Use of anticoagulants, corticosteroids, immunomodulators, or immunosuppressants
- Use of dietary and/or herbal supplements that can interfere with liver metabolism
- Use of any drugs known to induce or inhibit hepatic drug metabolism
- Use of prescription medication or over-the-counter products
- Depot injection/implant of any drug except birth control.
- Known diagnosis of diabetes mellitus.
- History of autoimmune disease
- Human immunodeficiency virus (HIV) infection
- Sero-positive for HCV, and/or history of delta virus hepatitis
- Hypertension: blood pressure > 150/100 mmHg
- History of cardiac rhythm disturbances
- Family history of congenital long QT syndrome/unexplained sudden cardiac death
- Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease
- History of malignancy, except 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
- Regularly uses alcohol within past 6 months (ie, more than 14 units of alcohol per week)
- Evidence of acute inflammation, sepsis, or hemolysis
- Diagnosed with a significant psychiatric disorder
- Use of drugs of abuse
- History of allergy to bee venom
- Use of investigational agents/devices within 30 days
- Current participation in an investigational study
- Clinically significant gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease
- History/presence of Gilbert's syndrome, conditions that interfere with absorption, distribution, metabolism, excretion of drugs
- Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction
- Clinically significant history/presence of uncontrolled systemic disease
- Donated blood (500 mL) within 7 days prior to study treatment administration
- History of fever within 2 weeks of screening
- Immunization/planned immunization with live attenuated vaccine except influenza vaccine
- Excessive exercise/physical activity within 7 days of screening/enrolment or during study
- History of coagulopathy or stroke within past 6 months, and/or concurrent anticoagulants
Sites / Locations
- Nucleus Network Ltd
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment Group
Arm Description
ARC-520 Injection
Outcomes
Primary Outcome Measures
Efficacy: To evaluate the depth and duration of HBsAg decline in response to a single dose of ARC 520 in combination with entecavir or tenofovir in patients with chronic HBV infection
Secondary Outcome Measures
Safety:To determine the safety and tolerability of ARC 520 through monitoring of adverse events, vital signs, physical exam changes, blood sampling for hematology, coagulation and chemistry and 12-lead ECGs
Pharmacokinetic parameters: Cmax, AUC0-24, AUClast, AUCinf, CL, V=CL/kel, kel, t1/2
Blood samples collected immediately prior to infusion and immediately prior to end of infusion, and 0.5,1,3,6,24,48 hrs post-infusion.
Allergenicity:Evaluate Allergenicity of ARC-520 through Bee Venom Allergy Test (IgE)
Full Information
NCT ID
NCT02349126
First Posted
January 20, 2015
Last Updated
August 12, 2015
Sponsor
Arrowhead Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02349126
Brief Title
Study of ARC-520 in Patient With Chronic Hepatitis B Virus
Study Type
Interventional
2. Study Status
Record Verification Date
August 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Company decision to pursue alternative clinical trial
Study Start Date
February 2015 (undefined)
Primary Completion Date
December 2015 (Anticipated)
Study Completion Date
March 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrowhead Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Patients with chronic HBV infection will receive ARC-520 in combination with entecavir or tenofovir and be evaluated for safety and efficacy.
Detailed Description
This is a single-center, open-label study of ARC-520 in combination with entecavir or tenofovir administered to patients with immune active chronic HBV infection. An iterative trial design is anticipated with potential inclusion of additional cohorts with anticipated enrollment of up to 60 patients. Patients who have signed a Human Research Ethics Committee approved informed consent, and have met all of the protocol eligibility criteria will continue receiving daily oral entecavir (0.5-1.0 mg/day) or daily oral tenofovir (300 mg/day) and a single IV injection of ARC-520. If a serious adverse event (SAE) deemed possibly or probably related to study drug should occur at any point during the study, any further dosing will be put on hold pending a complete review of safety data by the sponsor and the Principal Investigator. 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, AEs, 12-lead ECGs, concomitant medication, blood sample collection for hematology, coagulation, chemistry, PK and exploratory PD measures, HBV virology. Patients will be monitored for a total of 12 weeks. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Hepatitis B, HBV infection, Hepatitis B Surface Antigen
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment Group
Arm Type
Experimental
Arm Description
ARC-520 Injection
Intervention Type
Drug
Intervention Name(s)
ARC-520 Injection
Other Intervention Name(s)
ARC-520
Intervention Description
ARC-520 Injection is a liver-targeted antiviral therapeutic designed to treat chronic hepatitis B virus (HBV) infection via an RNA interference (RNAi) mechanism.
Primary Outcome Measure Information:
Title
Efficacy: To evaluate the depth and duration of HBsAg decline in response to a single dose of ARC 520 in combination with entecavir or tenofovir in patients with chronic HBV infection
Time Frame
Through Day 85 post-dosing
Secondary Outcome Measure Information:
Title
Safety:To determine the safety and tolerability of ARC 520 through monitoring of adverse events, vital signs, physical exam changes, blood sampling for hematology, coagulation and chemistry and 12-lead ECGs
Time Frame
Through Day 85 post-dosing
Title
Pharmacokinetic parameters: Cmax, AUC0-24, AUClast, AUCinf, CL, V=CL/kel, kel, t1/2
Description
Blood samples collected immediately prior to infusion and immediately prior to end of infusion, and 0.5,1,3,6,24,48 hrs post-infusion.
Time Frame
Post dosing on Days 1,2 & 3
Title
Allergenicity:Evaluate Allergenicity of ARC-520 through Bee Venom Allergy Test (IgE)
Time Frame
Within 30 days prior to first dose and at Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, 18 to 65 years of age
Written informed consent
No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment
No abnormal finding of clinical relevance
Diagnosis of immune active chronic HBV infection
> 6 months of continuous treatment with daily, oral entecavir or tenofovir
Exclusion Criteria:
Pregnant or lactating
Acute signs of hepatitis/other infection within 4 weeks of screening
Antiviral therapy other than entecavir or tenofovir within 3 months of screening
Prior treatment with interferon or a toll receptor agonist in last 12 months
Use of anticoagulants, corticosteroids, immunomodulators, or immunosuppressants
Use of dietary and/or herbal supplements that can interfere with liver metabolism
Use of any drugs known to induce or inhibit hepatic drug metabolism
Use of prescription medication or over-the-counter products
Depot injection/implant of any drug except birth control.
Known diagnosis of diabetes mellitus.
History of autoimmune disease
Human immunodeficiency virus (HIV) infection
Sero-positive for HCV, and/or history of delta virus hepatitis
Hypertension: blood pressure > 150/100 mmHg
History of cardiac rhythm disturbances
Family history of congenital long QT syndrome/unexplained sudden cardiac death
Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease
History of malignancy, except 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
Regularly uses alcohol within past 6 months (ie, more than 14 units of alcohol per week)
Evidence of acute inflammation, sepsis, or hemolysis
Diagnosed with a significant psychiatric disorder
Use of drugs of abuse
History of allergy to bee venom
Use of investigational agents/devices within 30 days
Current participation in an investigational study
Clinically significant gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease
History/presence of Gilbert's syndrome, conditions that interfere with absorption, distribution, metabolism, excretion of drugs
Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction
Clinically significant history/presence of uncontrolled systemic disease
Donated blood (500 mL) within 7 days prior to study treatment administration
History of fever within 2 weeks of screening
Immunization/planned immunization with live attenuated vaccine except influenza vaccine
Excessive exercise/physical activity within 7 days of screening/enrolment or during study
History of coagulopathy or stroke within past 6 months, and/or concurrent anticoagulants
Facility Information:
Facility Name
Nucleus Network Ltd
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
12. IPD Sharing Statement
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Study of ARC-520 in Patient With Chronic Hepatitis B Virus
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