Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02065336
Previous Study | Return to List | Next Study

A Multicenter Study to Determine the Depth and Duration of Hepatitis B Surface Antigen (HBsAg) Reduction After Single or Multiple Doses of ARC-520, in Combination With Entecavir in Patients With Chronic Hepatitis B Virus (HBV) Infection

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.
 
ClinicalTrials.gov Identifier: NCT02065336
Recruitment Status : Terminated (Company decision to discontinue trial)
First Posted : February 19, 2014
Results First Posted : July 3, 2019
Last Update Posted : July 3, 2019
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals

Brief Summary:
The purpose of this study is to determine whether ARC-520 in combination with entecavir is effective in the treatment of patients with chronic HBV Infection.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: ARC-520 Drug: Placebo Drug: entecavir Drug: chlorpheniramine Phase 2

Detailed Description:

Treatment with ARC-520 for injection is expected to reduce all HBV proteins and replicative intermediates via ribonucleic acid (RNA) interference. The magnitude of the reduction and duration of effect will depend on the dose. Since to date ARC-520 has not been administered to patients with chronic HBV infection, the effective therapeutic dose in patients with chronic HBV infection is unknown. This study is designed to assess the antiviral activity of ARC-520, especially its effect on HBsAg, in patients with chronic HBV infection at different dose levels.

This is a multicenter, randomized, double-blind, placebo-controlled, single-dose escalation study of ARC 520 in combination with entecavir administered to participants with hepatitis B virus e antigen (HBeAg)-negative (Cohorts 1 through 4) or HBeAg-positive (Cohort 5) immune active, chronic HBV infection, followed by a two-dose open-label cohort (Cohort 6), three open-label single-dose cohorts in treatment-naïve participants (Cohorts 7, 11 and 12) and an open-label multi-dose extension study (Cohorts 8, 9, 10). Cohort 6 will investigate ARC-520 in combination with entecavir administered in two doses to participants with HBeAg-positive immune-active chronic HBV infection. Cohorts 7, 11 and 12 will enroll treatment-naïve participants. Cohort 8 will only enroll participants previously completing Cohorts 1-4. Cohort 9 will only enroll participants previously completing Cohort 5 or 6. Cohort 10 will only enroll participants previously completing Cohort 7.

Participants 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, adverse events (AEs), 12-lead electrocardiograms (ECGs), concomitant medication, blood sample collection for hematology, coagulation, chemistry, pharmacokinetic (PK) and exploratory pharmacodynamic (PD) measures, urinalysis, HBV serology, HBV genotyping and sequencing, follicle stimulating hormone (FSH) testing and pregnancy testing for females of childbearing potential. Clinically significant changes including AEs will be followed until resolution, until the condition stabilizes, until the event is otherwise explained, or until the participant is lost to follow-up.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Determine the Depth and Duration of Hepatitis B Surface Antigen (HBsAg) Reduction After a Single Intravenous Dose of ARC-520 in Combination With Entecavir in Patients With Chronic Hepatitis B Virus (HBV) Infection, Followed by a Two-dose Open-label Cohort and Three Open-label Single-dose Cohorts in Treatment Naïve Patients, Including a Multi-dose Open-label Extension at a Single Center
Actual Study Start Date : March 2014
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Entecavir

Arm Intervention/treatment
Experimental: ARC-520 Cohort 1
a single intravenous (IV) dose of double-blind ARC-520 Injection 1.0 mg/kg in combination with entecavir administered to participants with HBeAg-negative immune active chronic HBV infection
Drug: ARC-520
Drug: entecavir
Other Name: Baraclude

Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Placebo Comparator: ARC-520 Cohort 2
a single IV dose of double-blind ARC-520 Injection 2.0 mg/kg in combination with entecavir administered to participants with HBeAg-negative immune active chronic HBV infection
Drug: ARC-520
Drug: entecavir
Other Name: Baraclude

Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 3
a single IV dose of double-blind ARC-520 Injection 3.0 mg/kg in combination with entecavir administered to participants with HBeAg-negative immune active chronic HBV infection
Drug: ARC-520
Drug: entecavir
Other Name: Baraclude

Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 4
a single IV dose of double-blind ARC-520 Injection 4.0 mg/kg in combination with entecavir administered to participants with HBeAg-negative immune active chronic HBV infection
Drug: ARC-520
Drug: entecavir
Other Name: Baraclude

Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 5
a single IV dose of double-blind ARC-520 Injection 4.0 mg/kg in combination with entecavir administered to participants with HBeAg-positive immune active chronic HBV infection
Drug: ARC-520
Drug: entecavir
Other Name: Baraclude

Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: Placebo Normal Saline Cohorts 1-5
a single IV dose of double-blind normal saline in combination with entecavir administered to participants with HBeAg-negative or -positive immune active chronic HBV infection
Drug: Placebo
Drug: entecavir
Other Name: Baraclude

Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 6
two IV doses of open-label ARC-520 2.0 mg/kg administered to participants with HBeAg-positive immune active chronic HBV
Drug: ARC-520
Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 7
a single IV dose of open-label ARC-520 4.0 mg/kg administered to treatment-naïve, HBeAg-negative or -positive participants with chronic hepatitis B (CHB)
Drug: ARC-520
Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 8
open-label multi-dose extension cohort: multiple IV doses of open-label ARC-520 (4.0 mg/kg every [Q]4 weeks) administered to HBeAg-negative participants with CHB receiving chronic entecavir therapy who completed Cohorts 1 through 4
Drug: ARC-520
Drug: entecavir
Other Name: Baraclude

Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 9
open-label multi-dose extension cohort: multiple IV doses of open-label ARC-520 (4.0 mg/kg Q6 weeks or Q8 weeks) administered to HBeAg-positive participants with CHB receiving chronic entecavir therapy who completed Cohorts 5 or 6
Drug: ARC-520
Drug: entecavir
Other Name: Baraclude

Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 10
open-label multi-dose extension cohort: multiple IV doses of open-label ARC-520 (4.0 mg/kg Q4 weeks) administered to a mixed cohort (HBeAg-negative and -positive participants) who were naïve (within the last 6 months) to entecavir treatment and completed Cohort 7
Drug: ARC-520
Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 11
a single IV dose of open-label ARC-520 5.0 mg/kg administered to treatment-naïve, HBeAg-positive participants with CHB
Drug: ARC-520
Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.

Experimental: ARC-520 Cohort 12
a single IV dose of open-label ARC-520 6.0 mg/kg administered to treatment-naïve, HBeAg-positive participants with CHB
Drug: ARC-520
Drug: chlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.




Primary Outcome Measures :
  1. Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) [ Time Frame: Baseline, through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 253 Cohort 10) ]

Secondary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 225 Cohort 10) ]
    An adverse event (AE) is any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. An SAE is any AE that: 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.Events were categorized as mild, moderate or severe. TEAEs were defined as all AEs starting or worsening after commencement of treatment with investigational product. A treatment-related TEAE was one whose relationship to treatment was noted as unlikely, possibly, or probably related.

  2. Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 [ Time Frame: Baseline, Day 29, Day 85 ]
    Bee venom allergy tests were used to assess immunoglobulin E (IgE) in Cohorts 1-7. Analysis values less than 0.35 kU/L were taken as negative.

  3. Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 [ Time Frame: Baseline, Days 1, 2, 3, 8, 15, 22, 29 ]
  4. Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24), Cohorts 1-5 [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]
  5. Pharmacokinetics of ARC-520 of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast), Cohorts 1-5 [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]
  6. Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf), Cohorts 1-5 Only [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]
  7. Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]
  8. Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]
  9. Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]
  10. Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]
  11. Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]
  12. Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 [ Time Frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose ]


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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Diagnosis of HBeAg negative and immune active chronic HBV infection (Cohorts 1-4, 8)
  • Diagnosis of HBeAg positive and immune active chronic HBV infection (Cohorts 5-6, 9)
  • Diagnosis of HBeAg negative or HBeAg positive and immune active or tolerant chronic HBV infection (Cohorts 7, 10, 11 & 12)
  • Patients with > 6 months of continuous, 0.5 mg/day oral entecavir, and a willingness to continue taking entecavir throughout the study (Cohorts 1-6, 8-9).
  • Patients naive to entecavir (never on entecavir or on entecavir <30 days prior to screening) and a willingness to take entecavir and willingness to continue taking entecavir throughout the study (Cohorts 7, 11 & 12).

Key Exclusion Criteria:

  • Female patients that have a positive pregnancy test or are lactating.
  • Acute signs of hepatitis/other infection (eg, moderate fever, jaundice, nausea, vomiting, and abdominal pain) evident within 4 weeks of screening and/or at the screening examination.
  • Patients with antiviral therapy other than entecavir within 3 months of screening or prior treatment with interferon or a toll receptor agonist in the last 5 years.
  • Use within the last 6 months or an anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants.
  • Has any history of autoimmune disease especially autoimmune hepatitis.
  • Has human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (sero-positive).
  • Is sero-positive for hepatitis C virus (HCV), and/or a history of delta virus hepatitis.
  • Has a history of allergy to bee venom or history of hypersensitivity reaction requiring an emergency visit to a physician or hospital and/or requirement for treatment with steroids and/or epinephrine.

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): NCT02065336


Locations
Layout table for location information
Hong Kong
Queen Mary Hospital
Pokfulam, Hong Kong
Prince of Wales Hospital
Shatin, Hong Kong
Sponsors and Collaborators
Arrowhead Pharmaceuticals
ICON Clinical Research
Investigators
Layout table for investigator information
Study Chair: Bruce Given, MD Arrowhead Pharmaceuticals, Inc.

Layout table for additonal information
Responsible Party: Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02065336     History of Changes
Other Study ID Numbers: Heparc-2001
First Posted: February 19, 2014    Key Record Dates
Results First Posted: July 3, 2019
Last Update Posted: July 3, 2019
Last Verified: April 2019
Keywords provided by Arrowhead Pharmaceuticals:
HBV
Hepatitis
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Chlorpheniramine
Entecavir
Antiviral Agents
Anti-Infective Agents
Antipruritics
Dermatologic Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Allergic Agents