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Study of ARC-520 in Patients With Chronic Hepatitis B Virus

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Arrowhead Pharmaceuticals
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02065336
First received: February 13, 2014
Last updated: April 27, 2016
Last verified: January 2016
  Purpose
The purpose of this study is to determine whether ARC-520 in combination with entecavir is effective in the treatment of patients with Chronic Hepatitis B Virus (HBV) Infection.

Condition Intervention Phase
Hepatitis B, Chronic
Drug: ARC-520
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

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 (HBsAG) as a measure of efficacy [ Time Frame: Through Day 85 (Cohorts 1-7, 11, 12); Through 24 weeks post last dose (Cohorts 8-10) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and frequency of adverse events as a measure of safety and tolerability [ Time Frame: Through Day 85 (Cohorts 1-7, 11, 12); Through 24 weeks post last dose (Cohorts 8-10) ] [ Designated as safety issue: Yes ]
  • Change from baseline in Immunoglobulin E (IgE) as a measure of allergenicity of ARC-520 [ Time Frame: Day 29 and Day 85 ] [ Designated as safety issue: Yes ]
    Cohorts 1-7 only

  • Change from baseline on entecavir plasma trough concentration [ Time Frame: Through Day 29 ] [ Designated as safety issue: No ]
    Cohorts 1-7 only

  • Pharmacokinetics of ARC-520: AUC0-24 (Cohorts 1-5 only) [ Time Frame: Through 48 hours post dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time 0 to 24 hours

  • Pharmacokinetics of ARC-520: AUClast (Cohorts 1-5 only) [ Time Frame: Through 48 hours post dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time 0 to the last quantifiable plasma concentration

  • Pharmacokinetics of ARC-520: AUCinf: Change over time (Cohorts 1-5 only) [ Time Frame: Through 48 hours post dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time 0 extrapolated to infinity

  • Pharmacokinetics of ARC-520: Cmax: Change over time (Cohorts 1-5 only) [ Time Frame: Through 48 hours post dose ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration

  • Pharmacokinetics of ARC-520: CL: Change over time (Cohorts 1-5 only) [ Time Frame: Through 48 hours post dose ] [ Designated as safety issue: No ]
    Clearance

  • Pharmacokinetics of ARC-520: V: Change over time (Cohorts 1-5 only) [ Time Frame: Through 48 hours post dose ] [ Designated as safety issue: No ]
    Apparent volume of distribution

  • Pharmacokinetics of ARC-520: kel: Change over time (Cohorts 1-5 only) [ Time Frame: Through 48 hours post dose ] [ Designated as safety issue: No ]
    Terminal elimination rate constant

  • Pharmacokinetics of ARC-520: t1/2: Change over time (Cohorts 1-5 only) [ Time Frame: Through 48 hours post dose ] [ Designated as safety issue: No ]
    Terminal elimination half-life


Estimated Enrollment: 136
Study Start Date: March 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARC-520 Cohorts 1-5
Single dose, IV ARC-520, 1.0, 2.0, 3.0 or 4.0 mg/kg
Drug: ARC-520
Placebo Comparator: Placebo Normal Saline Cohorts 1-5
Single dose, IV normal saline
Drug: Placebo
Experimental: ARC-520 Cohort 6
Two doses, IV ARC-520, 2.0 mg/kg
Drug: ARC-520
Experimental: ARC-520 Cohort 7
Single dose, IV ARC-520, 4.0 mg/kg
Drug: ARC-520
Experimental: ARC-520 Cohort 8
IV ARC-520, 4.0 mg/kg Q4 weeks
Drug: ARC-520
Experimental: ARC-520 Cohort 9
IV ARC-520, 4.0 mg/kg Q6 weeks or Q8 weeks
Drug: ARC-520
Experimental: ARC-520 Cohort 10, tx naive
IV ARC-520, 4.0 mg/kg Q4 weeks
Drug: ARC-520
Experimental: ARC-520 Cohort 11
Single dose, IV ARC-520, 5.0 mg/kg
Drug: ARC-520
Experimental: ARC-520 Cohort 12
Single dose, IV ARC-520, 6.0 mg/kg
Drug: ARC-520

Detailed Description:

Treatment with ARC-520 for injection is expected to reduce all HBV proteins and replicative intermediates via 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 it's 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 patients with 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 patients (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 patients with HBeAg positive immune active chronic HBV infection. Cohorts 7, 11 and 12 will enroll treatment naïve patients. Cohort 8 will only enroll subjects previously completing cohorts 1-4. Cohort 9 will only enroll subjects previously completing cohort 5 or 6. Cohort 10 will only enroll subjects previously completing cohort 7.

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, 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, 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 patient is lost to follow-up.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02065336

Contacts
Contact: Ivy Liu + 886 2 7706 6239 Ivy.Liu@iconplc.com
Contact: Diamond Martin +1 626-304-3400 dmartin@arrowheadpharma.com

Locations
Hong Kong
Queen Mary Hospital Recruiting
Pokfulam, Hong Kong
Contact: Ringo Wu    +852 2255-3579    rchwu@hkucc.hku.hk   
Principal Investigator: Man-Fung Yuen, MD, PhD         
Prince of Wales Hospital Active, not recruiting
Shatin, Hong Kong
Sponsors and Collaborators
Arrowhead Pharmaceuticals
ICON Clinical Research
Investigators
Study Chair: Bruce Given, MD Arrowhead Pharmaceuticals, Inc.
  More Information

Responsible Party: Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02065336     History of Changes
Other Study ID Numbers: Heparc-2001 
Study First Received: February 13, 2014
Last Updated: April 27, 2016
Health Authority: Hong Kong: Department of Health

Keywords provided by Arrowhead Pharmaceuticals:
HBV
Hepatitis

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on September 26, 2016