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

Primary Purpose

Chronic Hepatitis B

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ARC-520
Placebo
Entecavir
Tenofovir
diphenhydramine
Sponsored by
Arrowhead Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Hepatitis B Virus, Chronic Hepatitis B, HBV

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Kaiser Permanente
  • Univ. Of Miami School Of Medicine/Center For Liver Diseases
  • Ichan School of Medicine at Mount Sinai
  • The Texas Liver Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ARC-520

Placebo

Arm 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.

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.

Outcomes

Primary Outcome Measures

Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 85

Secondary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with treatment. An SAE was defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. An AE was classified as a TEAE if the AE was not present prior to the first study medication administration and started at or after the time of initiation of administration of study medication, or if the AE presented prior to initiation of administration of study medication, continued and increased in intensity after administration of study medication.
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast)
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)
Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax)
Pharmacokinetics of ARC-520: Apparent Clearance (CL)
Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V)
Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel)
Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2)
Pharmacokinetics of Entecavir or Tenofovir: AUC0-24
Pharmacokinetics of Entecavir or Tenofovir: AUClast
Pharmacokinetics of Entecavir or Tenofovir: Cmax
Pharmacokinetics of Entecavir or Tenofovir: Time of Cmax (Tmax)

Full Information

First Posted
May 15, 2015
Last Updated
October 31, 2017
Sponsor
Arrowhead Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02452528
Brief Title
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

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Terminated
Why Stopped
Company decision to discontinue trial
Study Start Date
August 2015 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrowhead Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

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 Virus, Chronic Hepatitis B, HBV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ARC-520
Arm Type
Experimental
Arm 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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
ARC-520
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Entecavir
Other Intervention Name(s)
Baraclude
Intervention Description
0.5 or 1.0 mg/day orally
Intervention Type
Drug
Intervention Name(s)
Tenofovir
Other Intervention Name(s)
Viread
Intervention Description
300 mg/day orally
Intervention Type
Drug
Intervention Name(s)
diphenhydramine
Intervention Description
50 mg orally as pretreatment antihistamine
Primary Outcome Measure Information:
Title
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 85
Time Frame
Baseline, Day 85
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to Adverse Events (AEs)
Description
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with treatment. An SAE was defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. An AE was classified as a TEAE if the AE was not present prior to the first study medication administration and started at or after the time of initiation of administration of study medication, or if the AE presented prior to initiation of administration of study medication, continued and increased in intensity after administration of study medication.
Time Frame
From time of informed consent through Day 147 ± 3 days
Title
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)
Time Frame
Through 48 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast)
Time Frame
Through 48 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)
Time Frame
Through 48 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax)
Time Frame
Through 48 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of ARC-520: Apparent Clearance (CL)
Time Frame
Through 48 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V)
Time Frame
Through 48 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel)
Time Frame
Through 48 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2)
Time Frame
Through 48 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of Entecavir or Tenofovir: AUC0-24
Time Frame
Through 24 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of Entecavir or Tenofovir: AUClast
Time Frame
Through 24 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of Entecavir or Tenofovir: Cmax
Time Frame
Through 24 hours post-dosing on Days 1 and 57
Title
Pharmacokinetics of Entecavir or Tenofovir: Time of Cmax (Tmax)
Time Frame
Through 24 hours post-dosing on Days 1 and 57

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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)
Facility Information:
Facility Name
Kaiser Permanente
City
San Francisco
State/Province
California
ZIP/Postal Code
94118
Country
United States
Facility Name
Univ. Of Miami School Of Medicine/Center For Liver Diseases
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Ichan School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
The Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States

12. IPD Sharing Statement

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

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