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    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2014-004751-31
    Sponsor's Protocol Code Number:Heparc-2003
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-03-13
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2014-004751-31
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial to assess a novel medicine in the treatment of patients with Chronic Hepatitis B Virus (HBV) Infection
    A.4.1Sponsor's protocol code numberHeparc-2003
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorArrowhead Research Corporation
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportArrowhead Research Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationICON Clinical Research
    B.5.2Functional name of contact pointIlse-Maria Nolan
    B.5.3 Address:
    B.5.3.1Street AddressSandyford Business Park
    B.5.3.2Town/ cityDublin
    B.5.3.3Post code18
    B.5.3.4CountryIreland
    B.5.4Telephone number35312564659
    B.5.6E-maililse-maria.nolan@iconplc.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameARC-520 Injection
    D.3.2Product code ARC-520
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot Yet Assigned
    D.3.9.1CAS number 1603138-54-0
    D.3.9.2Current sponsor codeAD0009 Duplex
    D.3.9.3Other descriptive nameAD0009: Cholesterol-conjugated siHBV-74
    D.3.9.4EV Substance CodeSUB171444
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number13
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot Yet Assigned
    D.3.9.1CAS number 1603138-75-5
    D.3.9.2Current sponsor codeAD0010 Duplex
    D.3.9.3Other descriptive nameAD0010: Cholesterol-conjugated siHBV-77
    D.3.9.4EV Substance CodeSUB171444
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number13
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Hepatitis B Virus Infection
    E.1.1.1Medical condition in easily understood language
    Chronic Hepatitis B Virus Infection
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level PT
    E.1.2Classification code 10008910
    E.1.2Term Chronic hepatitis B
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary Objective:
    To evaluate the depth of HBsAg decline in response to multiple doses of ARC-520 compared to PBO in patients with chronic HBV infection as a measure of drug activity
    E.2.2Secondary objectives of the trial
    Secondary Objectives:
    • To determine the incidence and frequency of adverse events possibly or probably related to treatment as a measure of safety and tolerability of ARC-520 when coadministered with a fixed dose of entecavir or tenofovir in patients with chronic HBV infection
    • To evaluate multi-dose pharmacokinetics (PK) of ARC-520 in patients with chronic HBV infection when coadministered with a fixed dose of entecavir or tenofovir in a subset of patients
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    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.
    OPTIONAL PHARMACOKINETIC SUBSTUDY
    E.3Principal inclusion criteria
    To be eligible for randomization, the following criteria must be met:
    1. Male or female, 18 to 75 years of age, inclusive, at the time of informed consent.
    2. Able to provide written informed consent prior to the performance of any study specific procedures.
    3. Body mass index (BMI) between 17.5 and 30.0 kg/m2, inclusive. BMI = weight (kg)/(height [m])2
    4. Have no abnormalities at screening or pre-dose 12-lead ECG assessment (measured after the patient is supine for at least 3 minutes) that, in the opinion of the principal investigator, may compromise patient’s safety in this study.
    5. Willing and able to comply with all study assessments and adhere to the protocol schedule.
    6. Have suitable venous access for blood sampling.
    7. Have no new abnormal finding of clinical relevance at the screening evaluation.
    8. Have a diagnosis of HBeAg positive, immune active, chronic HBV infection (HBsAg (+) for > 6 months) and all of the following:
    a. History of being HBsAg positive at 2 time points > 6 months apart, one of which can include at screening
    b. HBeAg positive at screening
    c. HBV DNA < 200 IU/mL at screening
    9. Patients with > 2 months of continuous treatment with daily, oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) and a willingness to continue taking entecavir or tenofovir throughout the study.
    10. Patients must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners) during the study and for 3 months following the last study treatment (ARC-520 or PBO). Males must not donate sperm for at least 3 months post-dose of the last study treatment. Male partners of female patients and female partners of male
    patients must also use contraception, if they are of childbearing potential. Females of childbearing potential must have a negative urine pregnancy test at screening and predose on Day 1. Females not of childbearing potential must be postmenopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed
    by follicle-stimulating hormone (FSH) level > 40 mIU/mL. Contraception that is deemed acceptable in this study includes the following:
    a. Condom
    b. Birth control pills (The Pill)
    c. Depot or injectable birth control (administered at least 3 months prior to planned study dose)
    d. Intrauterine device
    e. Birth Control Patch (eg, Ortho Evra®)
    f. NuvaRing®
    g. Surgical sterilization (ie, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women or vasectomy for men)
    Rhythm methods WILL NOT be considered as highly effective methods of contraception, however abstinence may be allowed based on opinion of treating physician.
    E.4Principal exclusion criteria
    A potential patient will be excluded from the study if any of the following criteria apply:
    1. Female patients have a positive pregnancy test or are lactating.
    2. Acute signs of hepatitis other severe infection (eg, moderate fever, jaundice, nausea, vomiting, and abdominal pain) evident within 4 weeks of screening and/or at the screening examination.
    3. Hepatic transaminases (ALT or AST) > 3X upper limits of normal at screening.
    4. Liver Elastography (i.e. FibroScan®) score > 9 at screening (if FibroScan® is not available, the following tests/criteria are acceptable: FibroTest/Fibrosure score > 0.59 n/a; Accoustic Radiation Force Impulse (ARFI, e.g Siemens Acuson) >1.55 m/s; Shear Wave Elastography (e.g. Aixplorer) >10.0 kPa at screening).
    5. Patients with antiviral therapy other than entecavir or tenofovir within 3 months of screening or prior treatment with interferon in the last 3 years.
    6. Use within the last 6 months or an anticipated requirement for anticoagulants, systemically administered corticosteroids, systemically administered immunomodulators, or systemically administered immunosuppressants.
    7. Use of prescription medication within 14 days prior to administration of study treatment that in the opinion of the PI or the Sponsor would interfere with study conduct. Topical products without systemic absorption, statins (except rosuvastatin), hypertensive medications, OTC and prescription pain medication or hormonal contraceptives (females) are acceptable.
    8. Has had a depot injection or implant of any drug within 3 months prior to administration of study treatment, with the exception of injectable/implantable birth control.
    9. Has a known diagnosis of Non-alcoholic steatohepatitis or homozygous or heterozygous familial hypercholesterolemia.
    10. Patients with any of the following laboratory abnormalities:
    a. Serum creatinine > 1.5 mg/dL (132.6 μmol/L)
    b. International normalized ratio (INR) > 1.25 × ULN
    c. Platelets < 100,000 cells per mL
    11. Has any history of poorly controlled autoimmune disease especially autoimmune hepatitis.
    12. Has human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (sero-positive).
    13. Is sero-positive for HCV, and/or a history of delta virus hepatitis.
    14. Has hypertension defined as blood pressure > 150/100 mmHg at screening confirmed by repeat. Patients with well-controlled blood pressure on hypertensive medication for > 2 months prior to study treatment administration will be allowed.
    15. Patients with a history of torsades de pointes, ventricular rhythm disturbances (eg, ventricular tachycardia or fibrillation), pathologic sinus bradycardia (heart rate < 50 bpm), 2nd degree or 3rd degree heart block, congenital long QT syndrome, prolonged QT interval due to medications, or new elevation or depression in the part of an ECG immediately following the QRS complex and merging into the T wave (ST segment) or new pathologic inverted T waves, or new pathologic Q waves on ECG. Patients with a history of atrial arrhythmias should be discussed with the sponsor Medical Monitor and CRO Medical Monitor.
    16. Has a family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death.
    17. Patients with a mean Fridericia corrected interval between the start of the Q wave and the end of the T wave (QTcF) > 450 msec for males and > 470 msec for females, following ECG tracings at screening.
    18. Has experienced symptomatic heart failure (per New York Heart Association guidelines [The Criteria Committee of the New York Heart Association 1994]), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction < 40%, transient ischemic attack, or cerebrovascular accident) within 6 months prior to study entry.
    19. Patients with a history of malignancy, including hepatocellular carcinoma within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Patients with other curatively treated malignancies who have no evidence of metastatic disease and are > 2 years disease-free may be entered following approval by the sponsor Medical Monitor and CRO Medical Monitor.
    20. Has had a major surgery within 3 months of screening.
    21. Has a history of alcohol and/or drug abuse < 12 months from screening.
    22. Regularly uses alcohol within 6 months prior to the screening visit (ie, more than 14 units of alcohol per week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).
    23. Diagnosed with a significant psychiatric disorder that is likely to impair subject participation in the study.Refer to the Protocol for Exclusion Criteria 24 - 42
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline to Day 113 in log qHBsAg will be evaluated by treatment and dose using a repeated measures mixed model.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 113
    E.5.2Secondary end point(s)
    A secondary analysis of change from baseline in log qHBsAg by visit will be evaluated by treatment and dose using an ANOVA model for each time point.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Each visit
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Hong Kong
    Korea, Republic of
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months12
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 39
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 9
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 24
    F.4.2.2In the whole clinical trial 48
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients who are not enrolled in the planned extension study (Heparc-2007) will be monitored for HBV virology,
    AEs, and exploratory PD measures for a total of 12 weeks after the last dose.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-06-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-06-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-12-15
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