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Extension Study of the Safety and Efficacy of Multi-dose Intravenous ARC-520 in Patients With Chronic Hepatitis B (HBV) Infection

Primary Purpose

Hepatitis B

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

ARC-520 Injection

entecavir

tenofovir

antihistamine

About this trial

This is an interventional treatment trial for Hepatitis B

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Queen Mary Hospital
Eugastro Gmbh
Pusan National University Hospital
Gachon University Gil Medical Center
Seoul National University Hospital
Severance Hospital, Yonsei University College of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ARC-520 Injection

Arm Description

Multiple administrations of ARC-520 starting at a dose level of 2 mg/kg, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Outcomes

Primary Outcome Measures

Percentage of Initial Responders to ARC-520 Therapy Achieving a 1-log Reduction in HBsAg at Week 36 Compared to Baseline

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.

Secondary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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.

Percentage of Initial Responders to ARC-520 Therapy With HBsAg Loss (Qualitative) Compared to Baseline Over Time

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.

Full Information

NCT ID

NCT02738008

First Posted

April 11, 2016

Last Updated

January 11, 2019

Sponsor

Arrowhead Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02738008

Brief Title

Extension Study of the Safety and Efficacy of Multi-dose Intravenous ARC-520 in Patients With Chronic Hepatitis B (HBV) Infection

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Terminated

Why Stopped

Company decision to discontinue trial

Study Start Date

March 2016 (undefined)

Primary Completion Date

December 2016 (Actual)

Study Completion Date

December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Arrowhead Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ARC-520 Injection

Arm Type

Experimental

Arm Description

Multiple administrations of ARC-520 starting at a dose level of 2 mg/kg, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Intervention Type

Drug

Intervention Name(s)

ARC-520 Injection

Intervention Description

IV injection

Intervention Type

Drug

Intervention Name(s)

entecavir

Intervention Description

All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.

Intervention Type

Drug

Intervention Name(s)

tenofovir

Intervention Description

All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.

Intervention Type

Drug

Intervention Name(s)

antihistamine

Intervention Description

All participants will be pretreated with an oral antihistamine. The antihistamine used should in general be an H1>H2 receptor blocker and would include diphenhydramine 50 mg, cetirizine 10 mg, chlorpheniramine 8 mg or hydroxyzine 50 mg. The Investigator is free to choose any of these antihistamines available locally and consistent with their country's Marketing Authorisation.

Primary Outcome Measure Information:

Title

Percentage of Initial Responders to ARC-520 Therapy Achieving a 1-log Reduction in HBsAg at Week 36 Compared to Baseline

Description

Time Frame

Baseline, Week 36

Secondary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Description

Time Frame

From first dose of study drug up to 28 weeks of treatment, plus up to 24 weeks of follow-up

Title

Percentage of Initial Responders to ARC-520 Therapy With HBsAg Loss (Qualitative) Compared to Baseline Over Time

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.

Time Frame

Baseline, Weeks 36, 48, and 60

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Facility Information:

Facility Name

Queen Mary Hospital

City

Hong Kong

ZIP/Postal Code

999077

Country

China

Facility Name

Eugastro Gmbh

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Pusan National University Hospital

City

Busan

ZIP/Postal Code

602-739

Country

Korea, Republic of

Facility Name

Gachon University Gil Medical Center

City

Incheon

ZIP/Postal Code

405-760

Country

Korea, Republic of

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

110-744

Country

Korea, Republic of

Facility Name

Severance Hospital, Yonsei University College of Medicine

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Extension Study of the Safety and Efficacy of Multi-dose Intravenous ARC-520 in Patients With Chronic Hepatitis B (HBV) Infection

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