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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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
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
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
Sex
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
1/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2016
Sample size
Target
Accrual to date
Final
47
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/ct2/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/ct2/show/NCT02797522