Trial record 91 of 511 for:    hepatitis b | Open Studies

A Multi-dose Study of ARC-520 in Patients With Hepatitis B 'e' Antigen (HBeAg) Negative, Chronic HBV Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Arrowhead Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02604199
First received: November 11, 2015
Last updated: April 27, 2016
Last verified: November 2015
  Purpose
Patients with chronic Hepatitis B Virus (HBV) infection will receive either ARC-520 or placebo in combination with entecavir or tenofovir, and be evaluated for safety and efficacy.

Condition Intervention Phase
Hepatitis B
Drug: ARC-520 Injection
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 Negative, 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 113 in response to multiple doses of ARC-520 versus placebo as a measure of efficacy. [ Time Frame: Baseline to Day 113 ] [ 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 169 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of ARC-520: AUC0-24 [ Time Frame: Through 48 hours post-dosing on Day 1 and Day 85 ] [ Designated as safety issue: No ]
    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 on Day 1 and Day 85 ] [ 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 [ Time Frame: Through 48 hours post-dosing on Day 1 and Day 85 ] [ 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 [ Time Frame: Through 48 hours post-dosing on Day 1 and Day 85 ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration

  • Pharmacokinetics of ARC-520: CL: Change over time [ Time Frame: Through 48 hours post-dosing on Day 1 and Day 85 ] [ Designated as safety issue: No ]
    Clearance

  • Pharmacokinetics of ARC-520: V: Change over time [ Time Frame: Through 48 hours post-dosing on Day 1 and Day 85 ] [ Designated as safety issue: No ]
    Apparent volume of distribution

  • Pharmacokinetics of ARC-520: kel: Change over time [ Time Frame: Through 48 hours post-dosing on Day 1 and Day 85 ] [ Designated as safety issue: No ]
    Terminal elimination rate constant

  • Pharmacokinetics of ARC-520: t1/2: Change over time [ Time Frame: Through 48 hours post-dosing on Day 1 and Day 85 ] [ Designated as safety issue: No ]
    Terminal elimination half-life


Estimated Enrollment: 60
Study Start Date: October 2015
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARC-520 Injection 1mg/kg
Intravenous ARC-520 at 1.0 mg/kg, once every 4 weeks for 4 doses
Drug: ARC-520 Injection
Placebo Comparator: Placebo
0,9% normal saline, once every 4 weeks for 4 doses
Other: Placebo
Experimental: ARC-520 Injection 2mg/kg
Intravenous ARC-520 at 2.0 mg/kg, once every 4 weeks for 4 doses
Drug: ARC-520 Injection

Detailed Description:
This is a multicenter, randomized, double-blind, placebo-controlled, multi-dose study of ARC-520 in combination with entecavir or tenofovir administered to patients with HBeAg negative and immune active chronic HBV infection. Eligible patients who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 or placebo in combination with entecavir or tenofovir. The study will enroll up to a total of 60 eligible chronic HBV infected patients. 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 assessment (AEs), 12-lead ECGs, liver fibrosis testing, concomitant medication assessment, blood sample collection for hematology, coagulation,chemistry, lactate, Pharmacokinetic (PK) measures (in a subset of patients), exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, Follicle Stimulating Hormone (FSH) testing (post-menopausal females) 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. For each patient, the duration of the study is approximately 33 weeks from screening to the Day 169 follow-up visit. For patients enrolling into a planned extension study, the total duration of this study is approximately 25 weeks from screening to Day 113 end of study visit.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, 18 to 75 years of age
  • Written informed consent
  • No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment
  • No new abnormal finding of clinical relevance at the screening evaluation.
  • Diagnosis of HBeAg negative, immune active, chronic HBV infection
  • > 2 months of continuous treatment with daily, oral entecavir or tenofovir
  • Willingness to continue taking entecavir or tenofovir throughout the study.
  • Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners)

Exclusion Criteria:

  • Pregnant or lactating
  • Acute signs of hepatitis/other infection within 4 weeks of screening
  • Antiviral therapy other than entecavir or tenofovir within 3 months of screening
  • Prior treatment with interferon in the last 3 years.
  • Use within the last 6 months or anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants.
  • Use of prescription medication within 14 days prior to treatment administration except: topical products without systemic absorption, statins (except rosuvastatin), hypertension medications, or hormonal contraceptives.
  • Depot injection or implant of any drug within 3 months prior to treatment administration, except injectable/implantable birth control.
  • Diagnosis of diabetes mellitus.
  • History of autoimmune disease especially autoimmune hepatitis.
  • Human immunodeficiency virus (HIV) infection.
  • Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis.
  • Hypertension defined as blood pressure > 150/100 mmHg
  • History of cardiac rhythm disturbances
  • Family history or 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, or in situ cervical cancer.
  • Has had a major surgery within 3 months of screening.
  • History of alcohol and/or drug abuse < 12 months from screening.
  • Regular uses of alcohol within 6 months prior to screening (ie, more than 14 units of alcohol per week).
  • Evidence of severe systemic acute inflammation, sepsis, or hemolysis.
  • Diagnosed with a significant psychiatric disorder.
  • Use of recreational drugs, such as marijuana, within 3 months prior to screening
  • Use of drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year prior to screening.
  • History of allergy to bee sting.
  • Use of investigational agents or devices within 30 days prior to planned study dosing or current participation in an investigational study.
  • Clinically significant history or presence of any gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease.
  • Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction.
  • Clinically significant history or presence of poorly controlled/uncontrolled systemic disease.
  • History of fever within 2 weeks of screening.
  • Immunized with a live attenuated vaccine within 7 days prior to dosing or planned vaccination (excluding flu vaccine by injection).
  • Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk.
  • Participated in excessive exercise/physical activity within 7 days of screening or planned during the trial.
  • History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s).
  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: NCT02604199

Contacts
Contact: Medical Director 626-304-3400

Locations
China
Queen Mary Hospital Recruiting
Hong Kong, China, 999077
Contact: Ringo WU    852 2255 3579    ringo.wu@gmail.com   
Principal Investigator: Man-Fung Yuen, MD         
Prince of Wales Hospital Recruiting
Hong Kong, China
Contact: Angel Chim       angelchim@cuhk.hk   
Principal Investigator: Henry LY Chan, MD         
Sub-Investigator: Grace Wong         
Sub-Investigator: Vincent Wong         
Germany
Klinikum der Johann Wolfgang Goethe Universitaet Recruiting
Frankfurt, Germany, 60590
Contact: Christiane Bolt    49 69 6301 5212    bolt@em.uni-frankfurt.de   
Contact: Anna Veith    069 6301 4544    Anna.Veith@kgu.de   
Principal Investigator: Stefan Zeuzem, MD         
Sub-Investigator: Tania Weizel         
Sub-Investigator: Stephanie Klein         
Sub-Investigator: Stefan Luhne         
Sub-Investigator: Judith Schrewe         
Asklepios Klinik St. Georg - Chirurgisch-Traumatologisches Zentrum Recruiting
Hamburg, Germany, 20099
Contact: Petra Lange    49 (0) 40 2840 760-201    lange@ifi-medizin.de   
Principal Investigator: Jorg Petersen, MD         
Sub-Investigator: Peter Buggisch         
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Olga Stoll    0511 532 6821    Stoll.Olga@mh-hannover.de   
Principal Investigator: Michael Manns, MD         
Sub-Investigator: Philipp Solbach         
Sub-Investigator: Markus Cornberg         
Sub-Investigator: Kerstin Port         
Sub-Investigator: Katja Deterding         
Sub-Investigator: Heinrich Wedemayer         
Eugastro Gmbh Recruiting
Leipzig, Germany, 04103
Contact: Michael Fuegemann    49 (0) 341/99395799    Michael.Fuegemann@eugastro.de   
Contact: Romy Reim    49 341 99395788    romy.reim@eugastro.de   
Principal Investigator: Ingolf Schiefke, MD         
Sub-Investigator: Albrecht Kretzschmar         
Universitaetsklinikum Leipzig Recruiting
Leipzig, Germany, 4103
Contact: Yvonne Hausmann    49 (0) 341 97 122 26    yvonne.hausmann@medizin.uni-leipzig.de   
Principal Investigator: Thomas Berg, MD         
Sub-Investigator: Johannes Wiegand         
Sub-Investigator: Florian van Boemmel         
Sub-Investigator: Balazs Fueloep         
Sub-Investigator: Albrecht Boehlig         
Sub-Investigator: Adam Herber         
Klinikum Der Ludwig-Maximilian-Universitaet Muenchen Recruiting
Muenchen, Germany, 81377
Contact: Birgit Stemplinger    089440073069    birgit.stemplinger@med.uni--muenchen.de   
Principal Investigator: Norbert H Greuner, MD         
Sub-Investigator: Bijan Raziorrouh         
Sub-Investigator: Nermina Bucan-Dedic         
Principal Investigator: Reinhart Zachoval         
University Hospital of Tuebingen Recruiting
Tuebingen, Germany, 72076
Contact: Petra Janke-Maier    49 7071/2982130    petra.janke-maier@med.uni-tuebingen.de   
Principal Investigator: Christoph Berg, MD         
Sub-Investigator: Christoph Werner         
Sub-Investigator: Daniel Egetemeyr         
Universitaetsklinikum Ulm, Klinik fur Innere Medizin I Recruiting
Ulm, Germany, 89081
Contact: Simone Bader    0731/500 44614    Simone.Bader@uniklinik-ulm.de   
Principal Investigator: Dietmar Klass, MD         
Sub-Investigator: Matthias Dollinger         
Sub-Investigator: Nektarios Dikopoulos         
Universitaetsklinikum Wuerzburg, Medizinische Klinik Und Poliklinik II Recruiting
Wuerzburg, Germany, 97080
Contact: Christine Schreier-Reinstaedtler    0931 201-40980    schreier_c1@ukw.de   
Principal Investigator: Hartwig Klinker, MD         
Sub-Investigator: Annegret Helle-Beyersdorf         
Sub-Investigator: Petra Schulze         
Sub-Investigator: Susanne Wiebecke         
Korea, Republic of
Pusan National University Hospital Recruiting
Busan, Korea, Republic of, 602-739
Contact: Hye Young Lee    82 512407869    prettyoung97@daum.net   
Principal Investigator: Jeong Heo, MD         
Sub-Investigator: Hyun Young Woo         
Gachon University Gil Medical Center Recruiting
Incheon, Korea, Republic of, 405-760
Contact: Sun Hwa Lee    82 1063758434    sunhwa.lee@gilhospital.com   
Principal Investigator: Ju Hyun Kim, MD         
Sub-Investigator: Duck Joo Choi         
Sub-Investigator: Yun Soo Kim         
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Jin Hee Kim    82 220722228    dadas3178@naver.com   
Principal Investigator: Jung-Hwan Yoon, MD         
Sub-Investigator: Jeong-Hoon Lee         
Severance Hospital, Yonsei University College of Medicine Recruiting
Seoul, Korea, Republic of, 120-752
Contact: Sin Ok Ki    82 2 312 4725    shinok74@yuhs.ac   
Contact: Sunjin Chung    82 2228 0525    archrose@yuhs.ac   
Principal Investigator: Sang Hoon Ahn, MD         
Sub-Investigator: Do Young Kim         
Sub-Investigator: Seung Up Kim         
Pusan National University Yangsan Hospital Recruiting
Yangsan-si Gyeongnam, Korea, Republic of, 626-770
Contact: Jin Ho Yang    82 553601738    pnuyhcrc@hanmail.net   
Principal Investigator: Ki Tae Yoon, MD         
Sub-Investigator: Mong Cho         
Sponsors and Collaborators
Arrowhead Pharmaceuticals
  More Information

Responsible Party: Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02604199     History of Changes
Other Study ID Numbers: Heparc-2002  2014-004145-27 
Study First Received: November 11, 2015
Last Updated: April 27, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
South Korea: Korea Food and Drug Administration (KFDA)

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

ClinicalTrials.gov processed this record on August 28, 2016