The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02797522




Registration number
NCT02797522
Ethics application status
Date submitted
8/06/2016
Date registered
13/06/2016
Date last updated
25/09/2018

Titles & IDs
Public title
A Study of ARC-521 Injection in Normal Adult Volunteers and Patients With Chronic Hepatitis B (CHB)
Scientific title
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
Secondary ID [1] 0 0
ARC5211001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARC-521 Injection
Other interventions - Placebo
Treatment: Drugs - antihistamine
Treatment: Drugs - acetaminophen
Treatment: Drugs - entecavir
Treatment: Drugs - tenofovir

Experimental: NHV Participants: Cohort 1 - NHV participants administered a single dose of ARC-521 Injection at a dose of 0.6 mg/kg.

Experimental: NHV Participants: Cohort 2 - NHV participants administered a single dose of ARC-521 Injection at a dose of 1 mg/kg.

Experimental: NHV Participants: Cohort 3 - NHV participants administered a single dose of ARC-521 Injection at a dose of 2 mg/kg.

Experimental: NHV Participants: Cohort 4 - NHV participants administered a single dose of ARC-521 Injection at a dose of 4 mg/kg.

Experimental: NHV Participants: Cohort 5 - NHV participants administered a single dose of ARC-521 Injection at a dose of 5 mg/kg.

Experimental: NHV Participants: Cohort 6 - NHV participants administered a single dose of ARC-521 Injection at a dose of 6 mg/kg.

Placebo Comparator: NHV Participants: Placebo - NHV participants administered 0.9% normal saline to match ARC-521 Injection at doses of 0.6, 1, 2, 4, 5 and 6 mg/kg.

Experimental: CHB Participants: Cohort 3b - Treatment-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).

Experimental: CHB Participants: Cohort 4b - Treatment-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).

Experimental: CHB Participants: Cohort 3c - Participants 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.

Experimental: CHB Participants: Cohort 4c - Participants 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.


Treatment: Drugs: ARC-521 Injection


Other interventions: Placebo
0.9% normal saline

Treatment: Drugs: antihistamine
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.

Treatment: Drugs: acetaminophen
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).

Treatment: Drugs: entecavir
Participants take entecavir OR tenofovir daily throughout the study.

Treatment: Drugs: tenofovir
Participants take entecavir OR tenofovir daily throughout the study.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
From first dose of study drug through Day 29 (± 1 day)
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
From first dose of study drug through Day 142 (± 3 days)
Primary outcome [3] 0 0
Pharmacokinetics of ARC-521 Injection: Area Under the Plasma-Concentration-Time Curve From Time 0-24 Hours (AUC0-24), Healthy Volunteers
Timepoint [3] 0 0
Through 48 hours post-dose on Day 1
Primary outcome [4] 0 0
Pharmacokinetics of ARC-521 Injection: Area Under the Plasma-Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast), Healthy Volunteers
Timepoint [4] 0 0
Through 48 hours post-dose on Day 1
Primary outcome [5] 0 0
Pharmacokinetics of ARC-521 Injection: Area Under the Plasma-Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf), Healthy Volunteers
Timepoint [5] 0 0
Through 48 hours post-dose on Day 1
Primary outcome [6] 0 0
Pharmacokinetics of ARC-521 Injection: Maximum Observed Plasma Concentration (Cmax), Healthy Volunteers
Timepoint [6] 0 0
Through 48 hours post-dose on Day 1
Primary outcome [7] 0 0
Pharmacokinetics of ARC-521 Injection: Clearance (CL), Healthy Volunteers
Timepoint [7] 0 0
Through 48 hrs post-dose on Day 1
Primary outcome [8] 0 0
Pharmacokinetics of ARC-521 Injection: Apparent Volume of Distribution (V), Healthy Volunteers
Timepoint [8] 0 0
Through 48 hours post-dose on Day 1
Primary outcome [9] 0 0
Pharmacokinetics of ARC-521 Injection: Terminal Elimination Rate Constant (Kel), Healthy Volunteers
Timepoint [9] 0 0
Through 48 hours post-dose on Day 1
Primary outcome [10] 0 0
Pharmacokinetics of ARC-521 Injection: Terminal Elimination Half-Life (t1/2), Healthy Volunteers
Timepoint [10] 0 0
Through 48 hours post-dose on Day 1
Primary outcome [11] 0 0
Change Over Time in Viral Antigens and DNA in CHB Participants as a Measure of Activity of ARC-521 Injection
Timepoint [11] 0 0
Baseline to Day 142
Secondary outcome [1] 0 0
Change Over Time in Cytokine Levels After Single and Multiple Doses of ARC-521 Injection
Timepoint [1] 0 0
Through 24 hours post-dose (Day 1 for NHVs, and Days 1, 29 & 57 for CHB participants)
Secondary outcome [2] 0 0
Change Over Time in Complement Levels After Single and Multiple Doses of ARC-521 Injection
Timepoint [2] 0 0
Through 24 hours post-dose (Day 1 for NHVs, and Days 1, 29 & 57 for CHB participants)

Eligibility
Key inclusion criteria
- 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- 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

- Regular use of alcohol within one month prior to the Screening visit (more than
fourteen units of alcohol per week)

- Evidence of severe systemic acute inflammation, sepsis, or hemolysis [NHVs only]

- Use within 3 months of illicit drugs (cocaine, phencyclidine [PCP],
3,4-methylenedioxymethamphetamine [MDMA], others) or positive test for drugs of abuse
at screening.

- History of allergy to bee venom or history of severe hypersensitivity reaction, such
as anaphylaxis

- Use of an investigational agent or device within 30 days prior to dosing or current
participation in an investigational study

- Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's
disease, hemochromatosis, or alpha-1 antitrypsin deficiency, liver or kidney disease

- Clinically significant history/presence of poorly controlled or decompensated
neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic,
psychiatric, metabolic, or other uncontrolled systemic disease

- Blood donation (500 mL) within 7 days prior to study treatment administration [NHVs
only]

- History of fever (>38.0ºC/100.4ºF) within 2 weeks of Screening [NHVs only]

- Any concomitant medical or psychiatric condition or social situation that impacts
compliance or involves additional safety risk

- History of coagulopathy (including deep vein thrombosis and pulmonary embolism) or
stroke within 6 months of baseline, and/or concurrent anticoagulant medication(s)

- Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT02797522
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02797522