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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
  Purpose
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.

Condition Intervention Phase
Chronic Hepatitis B Drug: ARC-520 Drug: Placebo Drug: Entecavir Drug: Tenofovir Drug: diphenhydramine Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Arrowhead Pharmaceuticals:

Primary Outcome Measures:
  • Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 85 [ Time Frame: Baseline, 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) [ 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 ]

Enrollment: 4
Study Start Date: August 2015
Study Completion Date: December 2016
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: ARC-520 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
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.

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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02452528


Locations
United States, California
Kaiser Permanente
San Francisco, California, United States, 94118
United States, Florida
Univ. Of Miami School Of Medicine/Center For Liver Diseases
Miami, Florida, United States, 33136
United States, New York
Ichan School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, Texas
The Texas Liver Institute
San Antonio, Texas, United States, 78215
Sponsors and Collaborators
Arrowhead Pharmaceuticals
  More Information

Responsible Party: Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02452528     History of Changes
Other Study ID Numbers: Heparc-2004
First Submitted: May 15, 2015
First Posted: May 22, 2015
Results First Submitted: October 5, 2017
Results First Posted: November 1, 2017
Last Update Posted: November 1, 2017
Last Verified: October 2017

Keywords provided by Arrowhead Pharmaceuticals:
Hepatitis B Virus
Chronic Hepatitis B
HBV

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Entecavir
Diphenhydramine
Promethazine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs