Study Stopped
Company decision to discontinue trial
A Study of ARC-521 Injection in Normal Adult Volunteers and Patients With Chronic Hepatitis B (CHB)
A Sequential Phase 1a/1b Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ARC-521 in Normal Adult Volunteers and Patients With Chronic Hepatitis B
1 other identifier
interventional
47
1 country
1
Brief Summary
Normal healthy volunteer (NHV) participants will enroll sequentially into a total of 6 escalating dose levels (6 subjects per dose level), randomized to receive a single dose of ARC-521 Injection or placebo. The maximum study duration for NHVs is approximately 21 weeks. Hepatitis B e Antigen (HBeAg)-negative participants with (CHB) will enroll sequentially into 3 dose levels (8 patients per dose level) to receive multiple doses of open label ARC-521 Injection. For each CHB participant the maximum study duration is approximately 37 weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2016
Shorter than P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2016
CompletedFirst Submitted
Initial submission to the registry
June 8, 2016
CompletedFirst Posted
Study publicly available on registry
June 13, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2016
CompletedResults Posted
Study results publicly available
September 25, 2018
CompletedJanuary 12, 2026
December 1, 2025
5 months
June 8, 2016
January 10, 2018
December 18, 2025
Conditions
Outcome Measures
Primary Outcomes (11)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs): Healthy Volunteers
An adverse event (AE) is any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. A serious AE 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.Events were categorized as mild, moderate or severe. TEAEs were defined as all AEs starting or worsening after commencement of treatment with investigational product. A treatment-related TEAE was one whose relationship to treatment was noted as unlikely, possibly, or probably related.
From first dose of study drug through Day 29 (± 1 day)
Number of Participants With TEAEs: CHB Participants
An AE is any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. A serious AE 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.Events were categorized as mild, moderate or severe. TEAEs were defined as all AEs starting or worsening after commencement of treatment with investigational product. A treatment-related TEAE was one whose relationship to treatment was noted as unlikely, possibly, or probably related.
From first dose of study drug through Day 142 (± 3 days)
Pharmacokinetics of ARC-521 Injection: Area Under the Plasma-Concentration-Time Curve From Time 0-24 Hours (AUC0-24), Healthy Volunteers
Through 48 hours post-dose on Day 1
Pharmacokinetics of ARC-521 Injection: Area Under the Plasma-Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast), Healthy Volunteers
Through 48 hours post-dose on Day 1
Pharmacokinetics of ARC-521 Injection: Area Under the Plasma-Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf), Healthy Volunteers
Through 48 hours post-dose on Day 1
Pharmacokinetics of ARC-521 Injection: Maximum Observed Plasma Concentration (Cmax), Healthy Volunteers
Through 48 hours post-dose on Day 1
Pharmacokinetics of ARC-521 Injection: Clearance (CL), Healthy Volunteers
Through 48 hrs post-dose on Day 1
Pharmacokinetics of ARC-521 Injection: Apparent Volume of Distribution (V), Healthy Volunteers
Through 48 hours post-dose on Day 1
Pharmacokinetics of ARC-521 Injection: Terminal Elimination Rate Constant (Kel), Healthy Volunteers
Through 48 hours post-dose on Day 1
Pharmacokinetics of ARC-521 Injection: Terminal Elimination Half-Life (t1/2), Healthy Volunteers
Through 48 hours post-dose on Day 1
Change Over Time in Viral Antigens and DNA in CHB Participants as a Measure of Activity of ARC-521 Injection
Baseline to Day 142
Secondary Outcomes (2)
Change Over Time in Cytokine Levels After Single and Multiple Doses of ARC-521 Injection
Through 24 hours post-dose (Day 1 for NHVs, and Days 1, 29 & 57 for CHB participants)
Change Over Time in Complement Levels After Single and Multiple Doses of ARC-521 Injection
Through 24 hours post-dose (Day 1 for NHVs, and Days 1, 29 & 57 for CHB participants)
Study Arms (11)
NHV Participants: Cohort 1
EXPERIMENTALNHV participants administered a single dose of ARC-521 Injection at a dose of 0.6 mg/kg.
NHV Participants: Cohort 2
EXPERIMENTALNHV participants administered a single dose of ARC-521 Injection at a dose of 1 mg/kg.
NHV Participants: Cohort 3
EXPERIMENTALNHV participants administered a single dose of ARC-521 Injection at a dose of 2 mg/kg.
NHV Participants: Cohort 4
EXPERIMENTALNHV participants administered a single dose of ARC-521 Injection at a dose of 4 mg/kg.
NHV Participants: Cohort 5
EXPERIMENTALNHV participants administered a single dose of ARC-521 Injection at a dose of 5 mg/kg.
NHV Participants: Cohort 6
EXPERIMENTALNHV participants administered a single dose of ARC-521 Injection at a dose of 6 mg/kg.
NHV Participants: Placebo
PLACEBO COMPARATORNHV participants administered 0.9% normal saline to match ARC-521 Injection at doses of 0.6, 1, 2, 4, 5 and 6 mg/kg.
CHB Participants: Cohort 3b
EXPERIMENTALTreatment-naive participants with CHB administered 3 doses of ARC-521 Injection at 2 mg/kg once every 4 weeks. Participants are treatment-naive if they have not been on continual nucleoside analog (NUC) therapy (any NUC) for at least 6 months prior to screening (or have never been on NUCs).
CHB Participants: Cohort 4b
EXPERIMENTALTreatment-naive participants with CHB administered 3 doses of ARC-521 Injection at 4 mg/kg once every 4 weeks. Participants are treatment-naive if they have not been on continual NUC therapy (any NUC) for at least 6 months prior to screening (or have never been on NUCs).
CHB Participants: Cohort 3c
EXPERIMENTALParticipants with CHB currently on NUCs (entecavir or tenofovir for at least 6 months) administered 3 doses of ARC-521 Injection at 2 mg/kg once every 4 weeks.
CHB Participants: Cohort 4c
EXPERIMENTALParticipants with CHB currently on NUCs (entecavir or tenofovir for at least 6 months) administered 3 doses of ARC-521 Injection at 4 mg/kg once every 4 weeks.
Interventions
Approximately two hours prior to ARC-521 or placebo administration, participants will be pre-treated with an oral antihistamine, selected by the investigator from the list of approved antihistamines that is available in that country. Approved antihistamines are: diphenhydramine 50 mg by mouth (PO), chlorpheniramine 8 mg PO, or hydroxyzine 50 mg PO.
Participants take entecavir OR tenofovir daily throughout the study.
Approximately two hours prior to ARC-521 or placebo administration, participants will be pre-treated with acetaminophen (500 - 1000 mg PO, per local strength availability).
Participants take entecavir OR tenofovir daily throughout the study.
Eligibility Criteria
You may qualify if:
- Male or female, 18 to 55 years of age inclusive (NHVs) or 18-65 years of age inclusive (CHBs), at the time of informed consent
- Able to provide written informed consent prior to the performance of any study specific procedures
- Body mass index (BMI) between 19.0 and 35.0 kg/m2, inclusive
- A 12-lead ECG at Screening and pre-dose assessment that, in the opinion of the investigator, has no abnormalities that compromise participant's safety in this study
- Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive (both male and female partners)
- Have suitable venous access for blood sampling
- No abnormal finding of clinical relevance at the Screening evaluation (NHVs only)
- Have a diagnosis of HbeAg-negative chronic HBV infection (CHB patients only)
- Treatment-naive or currently on entecavir/tenofovir for 6 months or longer
You may not qualify if:
- Pregnant or lactating
- Acute signs of hepatitis/other infection at Screening or at baseline
- Use within last 14 days or anticipated requirement for anticoagulants, systemic corticosteroids, immunomodulators, or immunosuppressants
- Use of prescription medication within 14 days prior to study treatment that in the opinion of the PI or the Sponsor would interfere with study conduct.
- Known diagnosis of non-alcoholic steatohepatitis \[NHVs only\] or familial hypercholesterolemia
- Taking interferon alpha (INFalpha) within 6 months of screening \[CHBs only\]
- History of poorly controlled autoimmune disease or history of autoimmune hepatitis
- Human immunodeficiency virus (HIV) infection
- Seropositive for HBV (NHVs only) or hepatitis C virus (HCV), and/or history of delta virus hepatitis
- Hypertension defined as blood pressure \> 170/100 mmHg at screening \[NHVs only\]
- A 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 within the last 5 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer
- History of major surgery within 3 months of Screening
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Research Site 1
Grafton, Auckland, 1011, New Zealand
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The ARC-521 Injection development program was terminated early for regulatory and business reasons secondary to findings occurring in a non-clinical toxicology study. Program termination was not due to safety findings in humans.
Results Point of Contact
- Title
- Chief Operating Officer
- Organization
- Arrowhead Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 8, 2016
First Posted
June 13, 2016
Study Start
June 1, 2016
Primary Completion
November 1, 2016
Study Completion
November 1, 2016
Last Updated
January 12, 2026
Results First Posted
September 25, 2018
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will not share