Hepatitis B, ChronicPhase 2NCT02631096
Study of ARB-001467 in Subjects With Chronic HBV Infection Receiving Nucleos(t)Ide Analogue Therapy
A Phase 2 study testing ARB-001467 in people with Hepatitis B, Chronic, run by Arbutus Biopharma Corporation at 4 sites in 2 countries.
Trial summary
The study is a phase 2a, single blind, randomized, placebo controlled, study evaluating the safety, anti-viral activity, and pharmacokinetics (PK) following multiple doses of intravenous ARB-001467 Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- ARB-001467
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Dec 2015to 18 May 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented chronic HBV infection for ≥12 months prior to Screening Visit.
- Quantitative HBsAg ≥1000 IU/mL at the Screening Visit.
- Subjects currently receiving entecavir and/or tenofovir for ≥12 months and HBV DNA undetectable.
Who cannot join
- Known co-infection with HIV, hepatitis C virus, and hepatitis D virus.
- Receiving or planning to receive systemic immunosuppressive medications during the study or ≤2 months prior to the first dose of study treatment.
- Receiving or planning to receive interferon during the study or ≤12 months prior to the first dose of study treatment.
- Significant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia.
- Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine ≤12 months prior to the Screening Visit.
- Any known pre-existing medical or psychiatric condition that could interfere with the subject's ability to provide informed consent or participate in study conduct, or that may confound study findings.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Australia3 sites
Monash Health, Gastroenterology and Hepatology
Clayton, Victoria, 3168
The Alfred, Gastroenterology and Hepatology
Melbourne, Victoria, 3004
Linear Clinical Research Ltd
Nedlands, Western Australia, 6009
About this study
Official title: A Phase 2a Single-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety, Anti Viral Activity, and Pharmacokinetics of ARB-001467 in Non Cirrhotic, HBeAg Negative and Positive Subjects With Chronic HBV Infection Receiving Nucleos(t)Ide Analogue Therapy
The study is a phase 2a, single blind, randomized, placebo controlled, study evaluating the safety, anti-viral activity, and pharmacokinetics (PK) following multiple doses of intravenous ARB-001467
Read the detailed description
Approximately 24 subjects will be enrolled in three cohorts: two cohorts of HBeAg-negative subjects and one cohort of HBeAg-positive subjects and 12 HbeAg-negative subjects will be enrolled in cohort 4. All subjects will be non-cirrhotic, with chronic hepatitis B virus (HBV) infection, and will have been receiving nucleos(t)ide-analogue (NA) therapy with entecavir or tenofovir for at least 12 months.
- Conditions
- Hepatitis B, Chronic
- Being tested
- ARB-001467, Placebo
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARB-001467Drug
An IV infusion of ARB-001467
PlaceboOther
Also called 0.9% sodium chloride
An IV infusion of placebo
| Study group | Role | What they receive |
|---|---|---|
| 0.2 mg/kg ARB-001467 or Placebo | Experimental | HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.2 mg/kg versus placebo once a month for 3 months Receives: Drug: ARB-001467; Other: Placebo |
| 0.4 mg/kg ARB-001467 or Placebo | Experimental | HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months Receives: Drug: ARB-001467; Other: Placebo |
| ARB-001467 or Placebo | Experimental | HBeAg-positive subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months Receives: Drug: ARB-001467; Other: Placebo |
| 0.4 mg/kg ARB-001467 | Experimental | HBeAg-negative subjects receive ARB-001467 at. 0.4 mg/kg (open label) bi-weekly for 5 treatments and then subjects with HBsAg ≤1000 IU/mL AND ≥1.0 log10 decrease from baseline at Day 71 will continue monthly dosing through 48 weeks Receives: Drug: ARB-001467 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and severity of treatment-emergent SAEs, discontinuations due to AEs, and laboratory abnormalities, by cohort, through 28 days after the last infusion of study treatment.
To evaluate the safety and tolerability of multiple doses of ARB-001467 in HBeAg-negative and HBeAg-positive subjects with chronic Hepatitis B virus infection who are receiving nucleos(t)ide analogue therapy
Measured: 28 days post last infusion
Secondary outcomes (5)
Evaluate ARB-001467 Maximum plasma concentration (Cmax) at multiple time points from baseline through Day 85; 28 days after the last infusion of study treatment (cohort 1-3) and Week 36 (Cohort 4).
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Measured: Up to 36 Weeks
Evaluate ARB-001467 Time to maximum plasma concentration (Tmax) at multiple time points from baseline through Day 85; 28 days after the last infusion of study treatment (cohort 1-3) and Week 36 (Cohort 4).
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Measured: Up to 36 Weeks
Evaluate ARB-001467 Area under the plasma concentration-time curve from the start of infusion to the last measurable concentration (AUC0-t) at multiple time points from baseline through Day 85 (cohort 1-3) and Week 36 (Cohort 4).
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Measured: Up to 36 Weeks
Evaluate additional parameters for ARB-001467 from plasma concentration-time curve from start of infusion and extrapolated to infinity (AUC0-t), inf) partial, AUCs, T1/2, volume of distribution (VD) and clearance (CL) -baseline through Day 85 or Week 36.
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Measured: Up to 36 Weeks
Evaluate antiviral activity of ARB 001467 for up to 72 weeks after the first dose of study treatment.
The proportion of subjects in each dose level cohort with ≥0.5 log10 HBsAg decrease from baseline at EOS, and for these subjects, the changes from baseline (expressed as percentage and log10 change) in the following virologic markers will be assessed throughout the study:
- Quantitative HBV surface antigen (HBsAg)
- Quantitative HBV surface antibody (HBsAb)
- Quantitative HBV DNA and HBV-RNA (viral load)
For the HBeAg positive cohort only:
- Quantitative HBV e antigen (HBeAg)
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2015 (estimated)
- Study startDec 2015
- Primary completion18 May 2018
- Study completion18 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arbutus Biopharma Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Patricia Mendez, MD, PhD, Study chair, Arbutus Biopharma Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02631096
- Sponsor's protocol ID
- ARB-001467-002
- Status last verified
- Jun 2018
- First submitted
- 7 Dec 2015
- Last updated
- 29 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Single-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety, Anti Viral Activity, and Pharmacokinetics of ARB-001467 in Non Cirrhotic, HBeAg Negative and Positive Subjects With Chronic HBV Infection Receiving Nucleos(t)Ide Analogue Therapy
- ClinicalTrials.gov ID
- NCT02631096
- Acronym / sponsor ID
- ARB-001467-002
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Arbutus Biopharma CorporationIndustry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- 18 May 2018 (actual)
- Study completion
- 18 May 2018 (actual)
- First posted
- 15 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a phase 2a, single blind, randomized, placebo controlled, study evaluating the safety, anti-viral activity, and pharmacokinetics (PK) following multiple doses of intravenous ARB-001467
Detailed description
Approximately 24 subjects will be enrolled in three cohorts: two cohorts of HBeAg-negative subjects and one cohort of HBeAg-positive subjects and 12 HbeAg-negative subjects will be enrolled in cohort 4. All subjects will be non-cirrhotic, with chronic hepatitis B virus (HBV) infection, and will have been receiving nucleos(t)ide-analogue (NA) therapy with entecavir or tenofovir for at least 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 0.2 mg/kg ARB-001467 or Placebo | Experimental | Drug: ARB-001467, Other: PlaceboHBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.2 mg/kg versus placebo once a month for 3 months |
| 0.4 mg/kg ARB-001467 or Placebo | Experimental | Drug: ARB-001467, Other: PlaceboHBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months |
| ARB-001467 or Placebo | Experimental | Drug: ARB-001467, Other: PlaceboHBeAg-positive subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months |
| 0.4 mg/kg ARB-001467 | Experimental | Drug: ARB-001467HBeAg-negative subjects receive ARB-001467 at. 0.4 mg/kg (open label) bi-weekly for 5 treatments and then subjects with HBsAg ≤1000 IU/mL AND ≥1.0 log10 decrease from baseline at Day 71 will continue monthly dosing through 48 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Documented chronic HBV infection for ≥12 months prior to Screening Visit.
- Quantitative HBsAg ≥1000 IU/mL at the Screening Visit.
- Subjects currently receiving entecavir and/or tenofovir for ≥12 months and HBV DNA undetectable.
Key exclusion criteria (6 listed)
- Known co-infection with HIV, hepatitis C virus, and hepatitis D virus.
- Receiving or planning to receive systemic immunosuppressive medications during the study or ≤2 months prior to the first dose of study treatment.
- Receiving or planning to receive interferon during the study or ≤12 months prior to the first dose of study treatment.
- Significant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia.
- Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine ≤12 months prior to the Screening Visit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARB-001467An IV infusion of ARB-001467 | Drug | 0.2 mg/kg ARB-001467 or Placebo, 0.4 mg/kg ARB-001467, 0.4 mg/kg ARB-001467 or Placebo, ARB-001467 or Placebo |
| PlaceboAlso: 0.9% sodium chlorideAn IV infusion of placebo | Other | 0.2 mg/kg ARB-001467 or Placebo, 0.4 mg/kg ARB-001467 or Placebo, ARB-001467 or Placebo |
Primary outcome
Frequency and severity of treatment-emergent SAEs, discontinuations due to AEs, and laboratory abnormalities, by cohort, through 28 days after the last infusion of study treatment.
Time frame: 28 days post last infusion
To evaluate the safety and tolerability of multiple doses of ARB-001467 in HBeAg-negative and HBeAg-positive subjects with chronic Hepatitis B virus infection who are receiving nucleos(t)ide analogue therapy
5 secondary outcomes
Evaluate ARB-001467 Maximum plasma concentration (Cmax) at multiple time points from baseline through Day 85; 28 days after the last infusion of study treatment (cohort 1-3) and Week 36 (Cohort 4).
Time frame: Up to 36 Weeks
Evaluate ARB-001467 Time to maximum plasma concentration (Tmax) at multiple time points from baseline through Day 85; 28 days after the last infusion of study treatment (cohort 1-3) and Week 36 (Cohort 4).
Time frame: Up to 36 Weeks
Evaluate ARB-001467 Area under the plasma concentration-time curve from the start of infusion to the last measurable concentration (AUC0-t) at multiple time points from baseline through Day 85 (cohort 1-3) and Week 36 (Cohort 4).
Time frame: Up to 36 Weeks
Evaluate additional parameters for ARB-001467 from plasma concentration-time curve from start of infusion and extrapolated to infinity (AUC0-t), inf) partial, AUCs, T1/2, volume of distribution (VD) and clearance (CL) -baseline through Day 85 or Week 36.
Time frame: Up to 36 Weeks
Evaluate antiviral activity of ARB 001467 for up to 72 weeks after the first dose of study treatment.
Time frame: Up to 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patricia Mendez, MD, PhD study chair
Arbutus Biopharma Corporation
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ARB-001467 in people with Hepatitis B, Chronic, run by Arbutus Biopharma Corporation at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency and severity of treatment-emergent SAEs, discontinuations due to AEs, and laboratory abnormalities, by cohort, through 28 days after the last infusion of study treatment. (time frame: 28 days post last infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2018.