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

This study has been terminated.
(Company decision to discontinue trial)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02452528
First Posted: May 22, 2015
Last Update Posted: November 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals
May 15, 2015
May 22, 2015
October 5, 2017
November 1, 2017
November 1, 2017
August 2015
December 2016   (Final data collection date for primary outcome measure)
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 85 [ Time Frame: Baseline, Day 85 ]
Change from baseline in quantitative hepatits B surface antigen (log qHBsAg) at Day 85 in response to multiple doses of ARC-520 versus placebo as a measure of efficacy. [ Time Frame: From baseline to Day 85 ]
Complete list of historical versions of study NCT02452528 on ClinicalTrials.gov Archive Site
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to Adverse Events (AEs) [ Time Frame: From time of informed consent through Day 147 ± 3 days ]
    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) [ Time Frame: Through 48 hours post-dosing on Days 1 and 57 ]
  • 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 ]
  • 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 ]
  • Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Through 48 hours post-dosing on Days 1 and 57 ]
  • Pharmacokinetics of ARC-520: Apparent Clearance (CL) [ Time Frame: Through 48 hours post-dosing on Days 1 and 57 ]
  • Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V) [ Time Frame: Through 48 hours post-dosing on Days 1 and 57 ]
  • Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel) [ Time Frame: Through 48 hours post-dosing on Days 1 and 57 ]
  • Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2) [ Time Frame: Through 48 hours post-dosing on Days 1 and 57 ]
  • Pharmacokinetics of Entecavir or Tenofovir: AUC0-24 [ Time Frame: Through 24 hours post-dosing on Days 1 and 57 ]
  • Pharmacokinetics of Entecavir or Tenofovir: AUClast [ Time Frame: Through 24 hours post-dosing on Days 1 and 57 ]
  • Pharmacokinetics of Entecavir or Tenofovir: Cmax [ Time Frame: Through 24 hours post-dosing on Days 1 and 57 ]
  • Pharmacokinetics of Entecavir or Tenofovir: Time of Cmax (Tmax) [ Time Frame: Through 24 hours post-dosing on Days 1 and 57 ]
  • Incidence and frequency of adverse events as a measure of safety and tolerability [ Time Frame: Through Day 147 ]
  • Pharmacokinetics of ARC-520: AUC0-24 [ Time Frame: Through 48 hours post-dosing ]
    Area under the plasma concentration-time curve from time 0 to 24 hours
  • Pharmacokinetics of ARC-520: AUClast [ Time Frame: Through 48 hours post-dosing ]
    Area under the plasma concentration-time curve from time 0 to the last quantifiable plasma concentration
  • Pharmacokinetics of ARC-520 - AUCinf: Change over time [ Time Frame: Through 48 hours post-dosing ]
    Area under the plasma concentration-time curve from time 0 extrapolated to infinity
  • Pharmacokinetics of ARC-520 - Cmax: Change over time [ Time Frame: Through 48 hours post-dosing ]
    Maximum observed plasma concentration
  • Pharmacokinetics of ARC-520 - CL: Change over time [ Time Frame: Through 48 hours post-dosing ]
    Clearance
  • Pharmacokinetics of ARC-520- V: Change over time [ Time Frame: Through 48 hours post-dosing ]
    Apparent volume of distribution
  • Pharmacokinetics of ARC-520 - kel: Change over time [ Time Frame: Through 48 hours post-dosing ]
    Terminal elimination rate constant
  • Pharmacokinetics of ARC-520 - t1/2: Change over time [ Time Frame: Through 48 hours post-dosing ]
    Terminal elimination half-life
  • Pharmacokinetics of entecavir or tenofovir - AUC0-24: Change over time [ Time Frame: Through 24 hours post-dosing ]
    Area under the plasma concentration-time curve from time 0 to 24 hours
  • Pharmacokinetics of entecavir or tenofovir - AUClast: Change over time [ Time Frame: Through 24 hours post-dosing ]
    Area under the plasma concentration-time curve from time 0 to the last quantifiable plasma concentration
  • Pharmacokinetics of entecavir or tenofovir - Cmax: Change over time [ Time Frame: Through 24 hours post-dosing ]
    Maximum observed plasma concentration
  • Pharmacokinetics of entecavir or tenofovir - tmax: Change over time [ Time Frame: Through 24 hours post-dosing ]
    Time of Cmax
Not Provided
Not Provided
 
Study of ARC-520 in Participants With Hepatitis B Virus e Antigen (HBeAg) Positive Chronic Hepatitis B Virus
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
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Chronic Hepatitis B
  • Drug: ARC-520
  • Drug: Placebo
  • Drug: Entecavir
    0.5 or 1.0 mg/day orally
    Other Name: Baraclude
  • Drug: Tenofovir
    300 mg/day orally
    Other Name: Viread
  • Drug: diphenhydramine
    50 mg orally as pretreatment antihistamine
  • Experimental: ARC-520

    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.

    Interventions:
    • Drug: ARC-520
    • Drug: Entecavir
    • Drug: Tenofovir
    • Drug: diphenhydramine
  • Placebo Comparator: Placebo

    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.

    Interventions:
    • Drug: Placebo
    • Drug: Entecavir
    • Drug: Tenofovir
    • Drug: diphenhydramine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4
December 2016
December 2016   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02452528
Heparc-2004
Yes
Not Provided
Not Provided
Arrowhead Pharmaceuticals
Arrowhead Pharmaceuticals
Not Provided
Not Provided
Arrowhead Pharmaceuticals
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP