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Trial record 3 of 58 for:    monarch

Study of ARC-520 With or Without Other Drugs Used in the Treatment of Chronic HBV (Monarch)

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ClinicalTrials.gov Identifier: NCT02577029
Recruitment Status : Terminated (Company decision to discontinue trial)
First Posted : October 15, 2015
Last Update Posted : January 19, 2017
Sponsor:
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals

Brief Summary:
Patients with chronic Hepatitis B Virus (HBV) infection will receive either ARC-520 alone or ARC-520 in combination with other treatments such as entecavir (ENT) or tenofovir (TDF) and/or pegylated interferon alpha 2a (PEG IFN) therapy, and be evaluated for safety and efficacy.

Condition or disease Intervention/treatment Phase
Hepatitis B Hepatitis D Drug: ARC-520 Drug: Entecavir Biological: Pegylated Interferon alpha 2a Drug: Tenofovir disoproxil Phase 2

Detailed Description:
This is a multicenter, open-label study of ARC-520 based treatment regimens administered to patients with HBeAg positive or HBeAg negative immune active chronic Hepatitis B Virus (HBV) infection of various genotypes, or patients with Hepatitis D Virus (HDV). Eligible patients naive to previous treatment, and who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 alone or ARC-520 plus additional treatments such as entecavir (ENT) or tenofovir (TDF) and/or pegylated interferon alpha 2a (PEG IFN) therapy. The study may initially involve up to a total of 96 eligible chronic HBV and HDV infected patients. Patients in all cohorts will receive a total of 13 doses of ARC-520 at 2mg/kg or 4 mg/kg. 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, exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, cytokines, 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 96 weeks, from enrolment to last visit. Prior to enrolment there is a 60 day screening period. Addition of new cohorts and additional treatment regimens are anticipated for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Study to Evaluate ARC-520 Administered Alone and in Combination With Other Therapeutics in Patients With Chronic Hepatitis B Virus (HBV) Infection (MONARCH)
Study Start Date : December 2015
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ARC-520 administered alone
ARC-520 (2 mg/kg or 4 mg/kg every 4 weeks) for 48 weeks (13 doses).
Drug: ARC-520
Experimental: ARC-520 with nucleoside and Peginterferon
ARC-520 (2 mg/kg every 4 weeks - 48 weeks) + entecavir (0.5 mg daily - about 60 weeks) or tenofovir (300 mg daily - about 60 weeks) + Peginterferon alpha 2a (180 mcg weekly) - 48 weeks
Drug: ARC-520
Drug: Entecavir
Other Name: Baraclude

Biological: Pegylated Interferon alpha 2a
Other Names:
  • Peginterferon
  • Pegasys

Drug: Tenofovir disoproxil
Other Name: Viread

Experimental: ARC-520 with Peginterferon
ARC-520 (2 mg/kg every 4 weeks - 48 weeks) + Peginterferon alpha 2a (180 mcg weekly) - 48 weeks
Drug: ARC-520
Biological: Pegylated Interferon alpha 2a
Other Names:
  • Peginterferon
  • Pegasys




Primary Outcome Measures :
  1. Percentage of patients achieving a 1-log reduction in Hepatitis B Surface Antigen (HBsAg) compared to baseline [ Time Frame: Baseline to Week 60 ]

Secondary Outcome Measures :
  1. Percentage of patients with HBsAg loss (based on qualitative assay) compared to baseline [ Time Frame: Baseline and Weeks 52, 60, 72 and 96 ]
  2. Percentage of patients achieving a 1-log reduction in HBsAg and achieving a HBsAg level < 100 IU/L compared to baseline [ Time Frame: Baseline and Weeks 52, 60, 72 and 96 ]
  3. Time to HBsAg loss [ Time Frame: Baseline through Week 96 ]
  4. Time to anti-HBs (antibody to Hepatitis B Surface Antigen) seroconversion [ Time Frame: Baseline through Week 96 ]
  5. Percentage of patients with anti-HBs seroconversion compared to baseline [ Time Frame: Baseline and Weeks 52, 60, 72 and 96 ]
  6. Percentage of patients with Hepatitis B e Antigen (HBeAg) loss and Anti Hepatitis B e Antigen (Anti-HBe) seroconversion compared to baseline (if HBeAg positive at study entry) [ Time Frame: Baseline and Weeks 52, 60, 72 and 96 ]
  7. Percentage of patients with resistance to ARC-520 compared from baseline to Week 52 [ Time Frame: Baseline and Week 52 ]
    Resistance defined as > 1.0 log IU/mL quantitative HBsAg (qHBsAg) increase from nadir, confirmed by repeat test.

  8. Percentage of patients with resistance to the combination therapy from baseline to Week 60 [ Time Frame: Baseline and Week 60 ]
    Resistance defined as > 1.0 log IU/mL increase in HBV DNA from nadir, confirmed by repeat test

  9. Incidence and frequency of adverse events as a measure of safety and tolerability of ARC-520 alone or when coadministered with combination therapy [ Time Frame: Baseline to Week 96 ]
  10. Percentage of HDV patients with undetectable HDV ribonucleic acid (RNA) after 48 weeks of concomitant ARC-520 and PEG IFN therapy [ Time Frame: At Weeks 52, 60, 72 and 96 ]
  11. Log change from baseline in quantitative HBV deoxyribonucleic acid (DNA) [ Time Frame: Baseline and Weeks 52, 60, 72 and 96 ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
  • Diagnosis of HBeAg negative or positive chronic HBV infection.
  • Must be HBsAg (+) during screening.
  • Must be treatment naïve: Never on pegylated interferon alpha 2a (PEG INF) and/or entecavir (ETV) or tenofovir (TDF); and
  • Have not used nucleoside/nucleotide analogs (NUCs) within the last 2 years prior to dosing on Day 1
  • 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 severe infections within 4 weeks of screening
  • Use within the last 14 days or anticipated requirement for anticoagulants, systemic 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, over-the-counter (OTC) and prescription pain medication or hormonal contraceptives
  • History of poorly controlled autoimmune disease or any history of autoimmune hepatitis
  • History of heterozygous or homozygous familial hypercholesterolemia.
  • Human immunodeficiency virus (HIV) infection
  • Is sero-positive for Hepatitis C Virus (HCV), or has a history of delta virus hepatitis (except for cohort in which delta virus infection is acceptable)
  • Has hypertension: blood pressure > 170/100 mmHg; well-controlled blood pressure on hypertensive medication allowed.
  • 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, or in situ cervical cancer
  • Has had major surgery within 1 month of screening
  • Regular use of alcohol within 6 months prior to screening (ie, more than 14 units of alcohol per week).
  • Use of recreational drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year prior to the screening.
  • History of allergy to bee sting
  • Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's disease, hemochromatosis, or alpha-1 antitrypsin deficiency
  • Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction
  • Clinically significant history or presence of poorly controlled/uncontrolled systemic disease
  • Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk
  • History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s)

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): NCT02577029


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Sponsors and Collaborators
Arrowhead Pharmaceuticals

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Responsible Party: Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02577029     History of Changes
Other Study ID Numbers: Heparc-2008
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: January 19, 2017
Last Verified: December 2016

Additional relevant MeSH terms:
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Hepatitis
Hepatitis A
Hepatitis B
Hepatitis D
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Interferons
Interferon alpha-2
Tenofovir
Interferon-alpha
Peginterferon alfa-2a
Entecavir
Antineoplastic Agents
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
Immunologic Factors
Physiological Effects of Drugs