Brief Summary
Chronic HBV patients will receive 9 doses of open-label ARC-520 once every 4 weeks and be evaluated for safety and efficacy.
Brief Title
Extension Study of the Safety and Efficacy of Multi-dose Intravenous ARC-520 in Patients With Chronic Hepatitis B (HBV) Infection
Detailed Description
Open-label, multi-center extension study of intravenous ARC-520 in combination with entecavir or tenofovir in patients with chronic HBV infection. Patients who successfully completed the Heparc-2002 (NCT02604199) and Heparc-2003 (NCT02604212) studies and responded to therapy are eligible to participate. Responders are defined as patients who showed a ½ log or greater reduction in their serum Hepatitis B Surface Antigen (HBsAg) levels from baseline to day 71 ± 3 days of the primary Heparc-2002 and Heparc-2003 studies. Patients who have signed a Human Research Ethics Committee approved informed consent and have met all of the protocol eligibility criteria will continue receiving daily oral entecavir or tenofovir and intravenous (IV) injections of ARC-520. Study visits will occur once every 4 weeks for a total of 9 visits for monitoring and ARC-520 administration.
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 medications, blood sample collection for hematology, coagulation, chemistry, creatine kinase, troponin, hemoglobin A1c, exploratory pharmacodynamic (PD) measures, urinalysis, HBV serology, immunogenicity, and pregnancy testing for females of childbearing potential. Patients will be monitored for HBV virology, AEs, and exploratory PD measures for a total of 24 weeks after the last dose of ARC-520.
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 medications, blood sample collection for hematology, coagulation, chemistry, creatine kinase, troponin, hemoglobin A1c, exploratory pharmacodynamic (PD) measures, urinalysis, HBV serology, immunogenicity, and pregnancy testing for females of childbearing potential. Patients will be monitored for HBV virology, AEs, and exploratory PD measures for a total of 24 weeks after the last dose of ARC-520.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hepatitis B
Eligibility Criteria
Inclusion Criteria:
* Patient showed a ½ log or greater reduction in serum HBsAg levels from baseline to Day 71 ± 3 days or Day 99 ± 3 days in the primary Heparc-2002 or Heparc-2003 study.
* Able to have first dose within 2 months of day 113 end-of-study visit in the primary Heparc-2002 or Heparc-2003 study.
* Able to provide written informed consent prior to the performance of any study specific procedures.
* Have no abnormalities in 12-lead ECG assessment that, in the opinion of the investigator, may compromise patient safety
* Willing and able to comply with all study assessments and adhere to the protocol schedule.
* Have no new abnormal finding of clinical relevance at the screening evaluation.
* Using 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 dose of (ARC 520).
Exclusion Criteria:
* Pregnant or lactating.
* Acute signs of hepatitis/other infection within 4 weeks of screening and/or at the screening examination.
* Use of prescription medication (including anticoagulants) within 14 days prior to administration of ARC-520.
* Has had major surgery within 3 months of screening.
* Has evidence of severe systemic acute inflammation, sepsis, or hemolysis.
* Diagnosed with a significant psychiatric disorder that would prevent participation in the study.
* Unable or unwilling to return for all scheduled study visits.
* Has any other condition that, in the opinion of the investigator, would render the patient unsuitable for enrollment, or could interfere with his/her participation in the study.
* Patient showed a ½ log or greater reduction in serum HBsAg levels from baseline to Day 71 ± 3 days or Day 99 ± 3 days in the primary Heparc-2002 or Heparc-2003 study.
* Able to have first dose within 2 months of day 113 end-of-study visit in the primary Heparc-2002 or Heparc-2003 study.
* Able to provide written informed consent prior to the performance of any study specific procedures.
* Have no abnormalities in 12-lead ECG assessment that, in the opinion of the investigator, may compromise patient safety
* Willing and able to comply with all study assessments and adhere to the protocol schedule.
* Have no new abnormal finding of clinical relevance at the screening evaluation.
* Using 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 dose of (ARC 520).
Exclusion Criteria:
* Pregnant or lactating.
* Acute signs of hepatitis/other infection within 4 weeks of screening and/or at the screening examination.
* Use of prescription medication (including anticoagulants) within 14 days prior to administration of ARC-520.
* Has had major surgery within 3 months of screening.
* Has evidence of severe systemic acute inflammation, sepsis, or hemolysis.
* Diagnosed with a significant psychiatric disorder that would prevent participation in the study.
* Unable or unwilling to return for all scheduled study visits.
* Has any other condition that, in the opinion of the investigator, would render the patient unsuitable for enrollment, or could interfere with his/her participation in the study.
Inclusion Criteria
Inclusion Criteria:
* Patient showed a ½ log or greater reduction in serum HBsAg levels from baseline to Day 71 ± 3 days or Day 99 ± 3 days in the primary Heparc-2002 or Heparc-2003 study.
* Able to have first dose within 2 months of day 113 end-of-study visit in the primary Heparc-2002 or Heparc-2003 study.
* Able to provide written informed consent prior to the performance of any study specific procedures.
* Have no abnormalities in 12-lead ECG assessment that, in the opinion of the investigator, may compromise patient safety
* Willing and able to comply with all study assessments and adhere to the protocol schedule.
* Have no new abnormal finding of clinical relevance at the screening evaluation.
* Using 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 dose of (ARC 520).
* Patient showed a ½ log or greater reduction in serum HBsAg levels from baseline to Day 71 ± 3 days or Day 99 ± 3 days in the primary Heparc-2002 or Heparc-2003 study.
* Able to have first dose within 2 months of day 113 end-of-study visit in the primary Heparc-2002 or Heparc-2003 study.
* Able to provide written informed consent prior to the performance of any study specific procedures.
* Have no abnormalities in 12-lead ECG assessment that, in the opinion of the investigator, may compromise patient safety
* Willing and able to comply with all study assessments and adhere to the protocol schedule.
* Have no new abnormal finding of clinical relevance at the screening evaluation.
* Using 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 dose of (ARC 520).
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT02738008
Org Class
Industry
Org Full Name
Arrowhead Pharmaceuticals
Org Study Id
Heparc-2007
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Multicenter, Extension Study of the Safety and Efficacy of Multi-dose Intravenous ARC-520 in Combination With Entecavir or Tenofovir in Patients With Chronic Hepatitis B Virus (HBV) Infection
Primary Outcomes
Outcome Description
Initial responders are defined as participants who showed a ½ log or greater reduction in their serum HBsAg levels from baseline to Day 71 ± 3 days of the primary Heparc-2002 and Heparc-2003 studies, where baseline is defined as the average of pre-dose values.
Outcome Measure
Percentage of Initial Responders to ARC-520 Therapy Achieving a 1-log Reduction in HBsAg at Week 36 Compared to Baseline
Outcome Time Frame
Baseline, Week 36
Secondary Ids
Secondary Id
2014-004201-33
Secondary Outcomes
Outcome Description
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. A TEAE was defined as an AE that was not present prior to the first study medication administration and started at/after the time of initiation of administration of study medication, or an AE which was present prior to initiation of study medication administration, which increased in severity after study medication administration.
Outcome Time Frame
From first dose of study drug up to 28 weeks of treatment, plus up to 24 weeks of follow-up
Outcome Measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Outcome Description
The qualitative HBsAg assay gives a binary result, positive or negative. Baseline is defined as the average of the pre-dose values in the primary Heparc-2002 and Heparc-2003 studies.
Outcome Time Frame
Baseline, Weeks 36, 48, and 60
Outcome Measure
Percentage of Initial Responders to ARC-520 Therapy With HBsAg Loss (Qualitative) Compared to Baseline Over Time
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Harmit Kalia
Investigator Email
hkalia@montefiore.org
Investigator Phone
347-443-1783
Categories Mesh Debug
Hepatitis --- HEPATITIS B
Blood Disorders --- BLOOD-BORNE INFECTIONS
HIV/AIDS --- BLOOD-BORNE INFECTIONS
Infectious Disease --- BLOOD-BORNE INFECTIONS
Hepatitis --- COMMUNICABLE DISEASES
HIV/AIDS --- COMMUNICABLE DISEASES
Infectious Disease --- COMMUNICABLE DISEASES
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
Hepatitis --- HEPATITIS, VIRAL, HUMAN
Hepatitis --- HEPATITIS
Digestive System --- LIVER DISEASES
Liver --- LIVER DISEASES
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- NEUROTRANSMITTER AGENTS
MeSH Terms
HEPATITIS B
BLOOD-BORNE INFECTIONS
COMMUNICABLE DISEASES
INFECTIONS
HEPADNAVIRIDAE INFECTIONS
DNA VIRUS INFECTIONS
VIRUS DISEASES
HEPATITIS, VIRAL, HUMAN
HEPATITIS
LIVER DISEASES
DIGESTIVE SYSTEM DISEASES
ARC-520
ENTECAVIR
TENOFOVIR
HISTAMINE ANTAGONISTS
ORGANOPHOSPHONATES
ORGANOPHOSPHORUS COMPOUNDS
ORGANIC CHEMICALS
ADENINE
PURINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
HISTAMINE AGENTS
NEUROTRANSMITTER AGENTS
MOLECULAR MECHANISMS OF PHARMACOLOGICAL ACTION
PHARMACOLOGIC ACTIONS
CHEMICAL ACTIONS AND USES
PHYSIOLOGICAL EFFECTS OF DRUGS