Hepatitis BPhase 2NCT02981602

Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV Infection

A Phase 2 study testing IONIS-HBVRx in people with Hepatitis B and Chronic Hepatitis B Atypical, run by GlaxoSmithKline at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To examine the safety and tolerability of IONIS-HBVRx administration to treatment-naive patients with chronic hepatitis B virus infection Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Hepatitis B, Chronic Hepatitis B Atypical
What is being tested?: IONIS-HBVRx
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 7 sitesin 2 countries
Study dates: 24 Feb 2017to 26 Dec 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Age 18 to 70 years
Chronic HBV infection ≥6 months (e.g., positive for serum HBsAg ≥ 6 months)
Plasma HBV DNA ≥ 2 x 1000 IU/mL (HBV DNA adequately suppressed for exploratory nucleos(t)ide analogue experienced cohort)
Serum HBsAg ≥ 50 IU/mL
Exploratory nucleos(t)ide analogue experienced cohort only: currently taking and have been taking tenofovir or entecavir without changes in drug, dose level and/or frequency of administration for ≥ 12 months and expect to continue taking without change through to the end of their participation in this study

Who cannot join

Current or prior receipt of anti-HBV nucleos(t)ide analogue therapy. Patients who have failed prior interferon treatment, greater than 6 months prior to Screening, may be evaluated for possible participation in the study (not applicable for exploratory nucleos(t)ide analogue experienced cohort)
History of liver cirrhosis and/or evidence of cirrhosis as determined by any of the following:
Liver biopsy (i.e., Metavir Score F4) within 2 years of Screening, or
Fibroscan > 12 KPa, within 12 months of Screening, or
AST-to-Platelet Index (APRI) > 2 and Fibrosure result > 0.7 within 12 months of Screening For patients without a test for cirrhosis in the above timeframes, Fibroscan, or APRI and Fibrosure, may be performed during the screening period to rule out cirrhosis
History of liver failure as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices

Show all 18Show fewer

History of liver disease other than Hepatitis B
Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV)
BMI > 35 kg/m2
History of, or suspected presence of vasculitis
Received solid organ or bone marrow transplant
Currently taking, or took within 3 months of Screening, any immunosuppressing drugs (e.g., prednisone)
Diagnosed hepatocellular carcinoma or suspected hepatocellular carcinoma as evidenced by screening alpha-fetoprotein ≥ 200 ng/mL. If the screening alpha-fetoprotein is ≥ 50 ng/mL and < 200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization
Clinically-significant abnormalities aside from chronic HBV infection in medical history (e.g., previous acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening, uncontrolled diabetes) or physical examination
History of bleeding diathesis or coagulopathy
History of extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis, polyarteritis nodosa)
History of excess alcohol consumption within 6 months of Screening
History of drug abuse or dependence, or recreational use of drugs: within 3 months of Screening for soft drugs (such as marijuana) and within 1-year of Screening for hard drugs (such as cocaine, phencyclidine [PCP])

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

South Korea6 sites

Korea University Ansan Hospital
Ansan
Inje University Busan Paik Hospital
Busan
Kyungpook National University Hospital
Daegu
Pusan National University Hospital
Pusan
Seoul National University Hospital
Seoul
Seoul St. Mary's Hospital
Seoul

Other trials in South Korea

Hong Kong1 site

Queen Mary Hospital
Hong Kong

Other trials in Hong Kong

About this study

Official title: A Phase 2, Double-Blinded, Randomized, Placebo-Controlled, Dose-Escalation Study to Examine the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ISIS 505358 in Treatment-Naïve Patients With Chronic HBV Infection

To examine the safety and tolerability of IONIS-HBVRx administration to treatment-naive patients with chronic hepatitis B virus infection

Read the detailed description

This study examines the effects of IONIS-HBVRx or placebo (3:1 randomization) administered subcutaneously to treatment-naïve patients who are chronically infected with HBV and the effects of subsequent nucleos(t)ide analogue treatment on these patients.

Conditions: Hepatitis B, Chronic Hepatitis B Atypical
Being tested: IONIS-HBVRx, Placebo
Keywords: Hepatitis, Chronic, HBV
Medical subject headings: Hepatitis B, Hepatitis, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IONIS-HBVRxDrug
Also called ISIS 505358
Ascending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection
PlaceboDrug
Placebo

Study groups in NCT02981602
Study group	Role	What they receive
IONIS-HBVRx	Experimental	Ascending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection Receives: Drug: IONIS-HBVRx
Placebo	Placebo comparator	Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%)
An adverse event is any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. Any adverse event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any important medical event according to medical judgment were categorized as SAE.
Measured: Up to Day 211
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time
Blood samples were collected for the analysis of clinical parameters including ALT, ALP, CK, GGT, LDH and AST. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time
Blood samples were collected for the analysis of clinical chemistry parameter-albumin and total protein. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate
Blood samples were collected for the analysis of clinical parameters including sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate, glucose, blood urea nitrogen (BUN), cholesterol and urate. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Outcome Measure Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine
Blood samples were collected for the analysis of clinical chemistry parameters: direct bilirubin, total bilirubin, indirect bilirubin and creatinine. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets
Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, WBC, lymphocytes, neutrophils, monocytes, and platelets at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline for Hematology Parameters: Hemoglobin
Blood samples were collected for the analysis of hematology parameters including hemoglobin at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline for Hematology Parameter: Hematocrit
Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline Values in Urine Specific Gravity
Urine samples were collected for the analysis of urine specific gravity. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value. Urine specific gravity is measured as the ratio of urine density compared with water density.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio
Urine samples were collected for the analysis of urine albumin/creatinine ratio and urine protein/creatinine ratio. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline Values in Urine Protein
Urine samples were collected for the analysis of urine protein. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time
Blood samples were collected for the analysis of blood coagulation factors:activated partial thromboplastin time (aPTT) and Prothrombin Time (PT). Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 23, 57, 85, 211
Change From Baseline Values in Blood Coagulation Factor: Prothrombin International Normalized Ratio
Blood samples were collected for the analysis of blood coagulation factor: Prothrombin International normalized ratio. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 23, 57, 85, 211
Change in Complement C3 Level at Worst Case Post Baseline Relative to Baseline
Blood samples were collected from participants to evaluate change in complement C3 level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement C3 was the minimum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and up to Day 211
Change in Complement C5a Level at Worst Case Post Baseline Relative to Baseline
Blood samples were collected from participants to evaluate change in complement C5a level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement C5a was the maximum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and up to Day 211
Change in Complement Bb Level at Worst Case Post Baseline Relative to Baseline
Blood samples were collected from participants to evaluate change in complement Bb level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement Bb was the maximum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and up to Day 211
Number of Participants With Reported Pregnancy
Female participants who were not surgically sterile or post-menopausal, underwent urine beta Human chorionic gonadotropin (Beta-HCG) pregnancy test.
Measured: Up to Day 211
Change From Baseline in Body Temperature
Body temperature was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline in Body Weight
Body weight was measured at indicated time points. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 211
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure
Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline in Respiratory Rate
Respiratory Rate was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Change From Baseline in Pulse Rate
Pulse Rate was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Number of Participants With Abnormal Findings in Physical Examination
Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems.
Measured: Up to Day 211
Number of Participants Who Received Atleast One Concomitant Medication
A concomitant medication is defined as any medication initiated after the first dose of study, or initiated prior to the first dose of study drug and continued after the first dose of study drug.
Measured: Up to Day 211
Change From Baseline in Electrocardiogram Mean Ventricular Rate
Triplicate 12-lead Electrocardiograms (ECGs) were recorded at indicated timepoints. At each time point, ECG machine automatically measured mean ventricular rate (VR). Baseline ECG was the average of the triplicate taken on Day 1 Pre-dose, if only 1 or 2 assessments were available, the single assessment or average of the 2 assessments was used. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose); Day1: 3 hours post-dose, 5 hours post-dose; Day 2; Day 22:pre-dose, 3 hours postdose, 5 hours post-dose; Days 23, 29 and 113
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula
Triplicate 12-lead Electrocardiograms (ECGs) were recorded at indicated timepoints. At each time point, ECG machine automatically measured QRS duration, uncorrected QT interval, QT corrected interval-Fredericia [QTcF] interval and QTc corrected by Bazett's formula (QTcB). Baseline ECG was the average of the triplicate taken on Day 1 Pre-dose, if only 1 or 2 assessments were available, the single assessment or average of the 2 assessments was used. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose); Day1: 3 hours post-dose, 5 hours post-dose; Day 2; Day 22:pre-dose, 3 hours postdose, 5 hours post-dose; Days 23, 29 and 113

Secondary outcomes (9)

Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Day 29
Blood samples were collected from participants to assess HBV DNA viral load. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value. The last observation carried forward (LOCF) method was used to impute missing values at Day 29 in this analysis.
Measured: Baseline (Day 1 pre-dose) and Day 29
Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Week 31
Blood samples were collected from participants to assess HBV DNA viral load. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Week 31
Change From Baseline in HBV Surface Antigen (HBsAg) Level in Serum at Day 29
Blood samples were collected from participants to assess HBsAg level. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value. The LOCF method was used to impute missing values at Day 29 in this analysis.
Measured: Baseline (Day 1 pre-dose) and Day 29
Change From Baseline in HBsAg Level in Serum at Week 31
Blood samples were collected from participants to assess HBsAg level. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1 pre-dose) and Week 31
Percentage of Participants Who Achieved HBsAg Loss at Day 29 and Week 31
Blood samples were collected to evaluate the percentage of participants with HBsAg loss at Day 29 and Week 31. A 'Loss' of HBsAg means antigen is negative. HBsAg Loss percentage is defined as number of participants with HBsAg loss divided by total number of participants assessed multiplied by 100. Baseline is the last non-missing measurement prior to the first dose of study drug.
Measured: At Day 29 and Week 31
Percentage of Participants Who Achieved HBV e Antigen (HBeAg) Loss at Day 29 and Week 31 Who Were HBeAg Positive at Baseline
Blood samples were collected to evaluate the percentage of participants with HBeAg loss at Day 29 and Week 31. A 'Loss' of HBeAg means antigen is negative. HBeAg Loss percentage is defined as number of participants with HBeAg loss divided by number of participants with positive HBeAg at Baseline multiplied by 100. Baseline is the last non-missing measurement prior to the first dose of study drug. Participants was considered HBeAg positive at Baseline if the Baseline value> 0.09 U/mL.
Measured: Baseline (Day 1, Pre dose) and at Day 29 and Week 31
Change From Baseline in Serum HBeAg Concentration at Day 29 in Participants Who Were HBeAg Positive at Baseline
Blood samples were collected from participants to assess HBeAg level. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value. Participant was considered HBeAg positive at Baseline if the Baseline value> 0.09 International Units/milliliter (IU/mL).
Measured: Baseline (Day 1, Pre dose) and at Day 29
Change From Baseline in Serum HBeAg Concentration at Week 31 in Participants Who Were HBeAg Positive at Baseline
Blood samples were collected from participants to assess HBeAg level. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value. Participant was considered HBeAg positive at Baseline if the Baseline value> 0.09 U/mL.
Measured: Baseline (Day 1, Pre dose) and Week 31
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection
Plasma samples were collected from participants with chronic HBV infection at indicated time points for pharmacokinetic analysis of GSK3228836.
Measured: Day 1:pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose, Days 2 and 23: 24 hours post-dose, Day 4: 72 hours post-dose, Days 8 and 15: pre-dose, Day 22: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose, and Days 29, 36, 57, 85, 113, and 211

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Feb 201726 Dec 2019

First posted5 Dec 2016 (estimated)
Study start24 Feb 2017
Primary completion18 Dec 2019
Study completion26 Dec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Hepatitis BStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02981602
Sponsor's protocol ID: 205695
Other IDs: ISIS 505358-CS3
Status last verified: Aug 2021
First submitted: 1 Dec 2016
Last updated: 10 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Delahaye JL, You S, Fu K, Van Buren S, Zhu C, Jordan W, Ray A, Freudenberg JM, Consalvo KM, Pagliaroli L, Joshi S, Dhawan P, Theodore D, Paff M, Walker J, Singh JM. Bepirovirsen induces innate immune proteins independent of HBV. Hepatol Int. 2026 Aug 4. doi: 10.1007/s12072-026-11134-z. Online ahead of print.
PubMed 42550463
Han K, Youssef AS, Magee M, Hood S, Tracey H, Kwoh J, Theodore D, Paff M, Nader A. Lack of Pharmacokinetic Drug-Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs. Clin Pharmacol Drug Dev. 2025 Apr;14(4):281-291. doi: 10.1002/cpdd.1518. Epub 2025 Feb 14.
PubMed 39950613
Yuen MF, Heo J, Jang JW, Yoon JH, Kweon YO, Park SJ, Tami Y, You S, Yates P, Tao Y, Cremer J, Campbell F, Elston R, Theodore D, Paff M, Bennett CF, Kwoh TJ. Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial. Nat Med. 2021 Oct;27(10):1725-1734. doi: 10.1038/s41591-021-01513-4. Epub 2021 Oct 12.
PubMed 34642494

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 10 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Double-Blinded, Randomized, Placebo-Controlled, Dose-Escalation Study to Examine the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ISIS 505358 in Treatment-Naïve Patients With Chronic HBV Infection
ClinicalTrials.gov ID: NCT02981602
Acronym / sponsor ID: 205695
Conditions: Hepatitis B, Chronic Hepatitis B Atypical
Keywords: Hepatitis, Chronic, HBV
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Collaborators: Ionis Pharmaceuticals, Inc.
Study start: 24 Feb 2017 (actual)
Primary completion: 18 Dec 2019 (actual)
Study completion: 26 Dec 2019 (actual)
First posted: 5 Dec 2016 (estimated)
Results: Posted 21 Dec 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To examine the safety and tolerability of IONIS-HBVRx administration to treatment-naive patients with chronic hepatitis B virus infection

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
IONIS-HBVRx	Experimental	Drug: IONIS-HBVRxAscending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection
Placebo	Placebo comparator	Drug: PlaceboSterile Normal Saline (0.9% NaCl) calculated volume to match active comparator

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Age 18 to 70 years
Chronic HBV infection ≥6 months (e.g., positive for serum HBsAg ≥ 6 months)
Plasma HBV DNA ≥ 2 x 1000 IU/mL (HBV DNA adequately suppressed for exploratory nucleos(t)ide analogue experienced cohort)
Serum HBsAg ≥ 50 IU/mL
Exploratory nucleos(t)ide analogue experienced cohort only: currently taking and have been taking tenofovir or entecavir without changes in drug, dose level and/or frequency of administration for ≥ 12 months and expect to continue taking without change through to the end of their participation in this study

Key exclusion criteria (18 listed)

Current or prior receipt of anti-HBV nucleos(t)ide analogue therapy. Patients who have failed prior interferon treatment, greater than 6 months prior to Screening, may be evaluated for possible participation in the study (not applicable for exploratory nucleos(t)ide analogue experienced cohort)
History of liver cirrhosis and/or evidence of cirrhosis as determined by any of the following:
History of liver failure as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices
History of liver disease other than Hepatitis B
Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV)

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
IONIS-HBVRxAlso: ISIS 505358Ascending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection	Drug	IONIS-HBVRx
PlaceboPlacebo	Drug	Placebo

Primary outcome

Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%)
Time frame: Up to Day 211
An adverse event is any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. Any adverse event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any important medical event according to medical judgment were categorized as SAE.
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Blood samples were collected for the analysis of clinical parameters including ALT, ALP, CK, GGT, LDH and AST. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Blood samples were collected for the analysis of clinical chemistry parameter-albumin and total protein. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate
Time frame: Outcome Measure Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Blood samples were collected for the analysis of clinical parameters including sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate, glucose, blood urea nitrogen (BUN), cholesterol and urate. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Blood samples were collected for the analysis of clinical chemistry parameters: direct bilirubin, total bilirubin, indirect bilirubin and creatinine. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, WBC, lymphocytes, neutrophils, monocytes, and platelets at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline for Hematology Parameters: Hemoglobin
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Blood samples were collected for the analysis of hematology parameters including hemoglobin at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline for Hematology Parameter: Hematocrit
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline Values in Urine Specific Gravity
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Urine samples were collected for the analysis of urine specific gravity. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value. Urine specific gravity is measured as the ratio of urine density compared with water density.
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Urine samples were collected for the analysis of urine albumin/creatinine ratio and urine protein/creatinine ratio. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline Values in Urine Protein
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Urine samples were collected for the analysis of urine protein. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time
Time frame: Baseline (Day 1 pre-dose) and Days 23, 57, 85, 211
Blood samples were collected for the analysis of blood coagulation factors:activated partial thromboplastin time (aPTT) and Prothrombin Time (PT). Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline Values in Blood Coagulation Factor: Prothrombin International Normalized Ratio
Time frame: Baseline (Day 1 pre-dose) and Days 23, 57, 85, 211
Blood samples were collected for the analysis of blood coagulation factor: Prothrombin International normalized ratio. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change in Complement C3 Level at Worst Case Post Baseline Relative to Baseline
Time frame: Baseline (Day 1 pre-dose) and up to Day 211
Blood samples were collected from participants to evaluate change in complement C3 level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement C3 was the minimum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change in Complement C5a Level at Worst Case Post Baseline Relative to Baseline
Time frame: Baseline (Day 1 pre-dose) and up to Day 211
Blood samples were collected from participants to evaluate change in complement C5a level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement C5a was the maximum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change in Complement Bb Level at Worst Case Post Baseline Relative to Baseline
Time frame: Baseline (Day 1 pre-dose) and up to Day 211
Blood samples were collected from participants to evaluate change in complement Bb level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement Bb was the maximum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Number of Participants With Reported Pregnancy
Time frame: Up to Day 211
Female participants who were not surgically sterile or post-menopausal, underwent urine beta Human chorionic gonadotropin (Beta-HCG) pregnancy test.
Change From Baseline in Body Temperature
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Body temperature was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline in Body Weight
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 211
Body weight was measured at indicated time points. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline in Respiratory Rate
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Respiratory Rate was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline in Pulse Rate
Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211
Pulse Rate was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.
Number of Participants With Abnormal Findings in Physical Examination
Time frame: Up to Day 211
Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems.
Number of Participants Who Received Atleast One Concomitant Medication
Time frame: Up to Day 211
A concomitant medication is defined as any medication initiated after the first dose of study, or initiated prior to the first dose of study drug and continued after the first dose of study drug.
Change From Baseline in Electrocardiogram Mean Ventricular Rate
Time frame: Baseline (Day 1 pre-dose); Day1: 3 hours post-dose, 5 hours post-dose; Day 2; Day 22:pre-dose, 3 hours postdose, 5 hours post-dose; Days 23, 29 and 113
Triplicate 12-lead Electrocardiograms (ECGs) were recorded at indicated timepoints. At each time point, ECG machine automatically measured mean ventricular rate (VR). Baseline ECG was the average of the triplicate taken on Day 1 Pre-dose, if only 1 or 2 assessments were available, the single assessment or average of the 2 assessments was used. Change from Baseline is defined as post-dose visit value minus Baseline value.
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula
Time frame: Baseline (Day 1 pre-dose); Day1: 3 hours post-dose, 5 hours post-dose; Day 2; Day 22:pre-dose, 3 hours postdose, 5 hours post-dose; Days 23, 29 and 113
Triplicate 12-lead Electrocardiograms (ECGs) were recorded at indicated timepoints. At each time point, ECG machine automatically measured QRS duration, uncorrected QT interval, QT corrected interval-Fredericia [QTcF] interval and QTc corrected by Bazett's formula (QTcB). Baseline ECG was the average of the triplicate taken on Day 1 Pre-dose, if only 1 or 2 assessments were available, the single assessment or average of the 2 assessments was used. Change from Baseline is defined as post-dose visit value minus Baseline value.

9 secondary outcomes

Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Day 29
Time frame: Baseline (Day 1 pre-dose) and Day 29
Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Week 31
Time frame: Baseline (Day 1 pre-dose) and Week 31
Change From Baseline in HBV Surface Antigen (HBsAg) Level in Serum at Day 29
Time frame: Baseline (Day 1 pre-dose) and Day 29
Change From Baseline in HBsAg Level in Serum at Week 31
Time frame: Baseline (Day 1 pre-dose) and Week 31
Percentage of Participants Who Achieved HBsAg Loss at Day 29 and Week 31
Time frame: At Day 29 and Week 31
Percentage of Participants Who Achieved HBV e Antigen (HBeAg) Loss at Day 29 and Week 31 Who Were HBeAg Positive at Baseline
Time frame: Baseline (Day 1, Pre dose) and at Day 29 and Week 31
Change From Baseline in Serum HBeAg Concentration at Day 29 in Participants Who Were HBeAg Positive at Baseline
Time frame: Baseline (Day 1, Pre dose) and at Day 29
Change From Baseline in Serum HBeAg Concentration at Week 31 in Participants Who Were HBeAg Positive at Baseline
Time frame: Baseline (Day 1, Pre dose) and Week 31
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection
Time frame: Day 1:pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose, Days 2 and 23: 24 hours post-dose, Day 4: 72 hours post-dose, Days 8 and 15: pre-dose, Day 22: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose, and Days 29, 36, 57, 85, 113, and 211

Results and safety

Results posted to the registry on 21 Dec 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1 GSK3228836 150 mg	6	6
Cohort 2 and Cohort 3 GSK3228836 300 mg	12	12
Cohorts 1-3 Placebo	6	6
Cohort 4 GSK3228836 300 mg	5	4
Cohort 4 Placebo	2	2

Primary outcome: Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%)

Time frame: Up to Day 211. Count of participants. Unit: Participants

Measure	Cohort 1 GSK3228836 150 mg n = 6	Cohort 2 and Cohort 3 GSK3228836 300 mg n = 12	Cohorts 1-3 Placebo n = 6	Cohort 4 GSK3228836 300 mg n = 5	Cohort 4 Placebo n = 2
Non-SAE (>=5%)	5	6	2	3	0
SAE	0	1	0	0	0

Population analysed: Safety Population includes all randomized participants who received at least 1 dose of GSK3228836 or placebo. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Primary outcome: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time

Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211. Mean (Standard Deviation). Unit: Units per liter (U/L)

Measure	Cohort 1 GSK3228836 150 mg n = 6	Cohort 2 and Cohort 3 GSK3228836 300 mg n = 12	Cohorts 1-3 Placebo n = 6	Cohort 4 GSK3228836 300 mg n = 5	Cohort 4 Placebo n = 2
ALT, Day29, n= 6,12,6,4,2	15.7 (56.65)	52.5 (112.14)	-0.7 (8.91)	45.3 (32.10)	-0.5 (3.54)
ALT, Day57, n= 5,12,6,4,2	45.6 (60.06)	37.5 (58.31)	-2.2 (8.77)	46.0 (42.31)	1.0 (3.54)
ALT, Day85, n= 6,12,6,4,2	-10.5 (30.20)	8.8 (29.87)	0.5 (9.14)	7.5 (13.18)	-0.5 (0.71)
ALT, Day211, n= 6,12,6,4,2	-24.3 (43.68)	-16.2 (30.75)	-3.2 (12.88)	6.5 (9.95)	5.5 (3.54)
ALP, Day29, n= 6,12,6,4,2	-3.2 (8.23)	5.2 (14.60)	-0.7 (8.12)	9.8 (11.95)	0.0 (0.90)
ALP, Day57, n= 5,12,6,4,2	7.8 (12.09)	13.3 (14.55)	8.0 (11.31)	1.3 (9.22)	4.0 (5.66)
ALP, Day85, n= 6,12,6,4,2	7.2 (7.73)	9.9 (9.24)	7.7 (9.89)	0.0 (4.24)	6.0 (4.24)
ALP, Day211, n= 6,12,6,4,2	18.2 (10.32)	11.3 (13.61)	9.3 (8.71)	1.5 (7.85)	5.0 (11.31)

Population analysed: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Primary outcome: Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time

Time frame: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211. Mean (Standard Deviation). Unit: Grams per liter

Measure	Cohort 1 GSK3228836 150 mg n = 6	Cohort 2 and Cohort 3 GSK3228836 300 mg n = 12	Cohorts 1-3 Placebo n = 6	Cohort 4 GSK3228836 300 mg n = 5	Cohort 4 Placebo n = 2
Albumin, Day29, n= 6,12,6,4,2	-0.8 (1.47)	0.3 (2.23)	-1.3 (1.51)	3.0 (2.16)	1.5 (3.54)
Albumin, Day57, n= 5,12,6,4,2	0.6 (1.67)	1.7 (2.57)	0.0 (1.55)	1.8 (1.50)	5.5 (0.71)
Albumin, Day85, n= 6,12,6,4,2	0.0 (2.00)	2.0 (3.28)	-0.8 (3.19)	1.3 (2.22)	3.0 (2.83)
Albumin, Day211, n= 6,12,6,4,2	1.0 (2.28)	3.3 (2.26)	0.7 (3.01)	4.3 (0.50)	3.0 (5.66)
Total Protein, Day29, n= 6,12,6,4,2	-1.8 (2.64)	1.9 (3.18)	-1.8 (4.75)	6.5 (3.11)	1.5 (7.78)
Total Protein, Day57, n= 5,12,6,4,2	0.8 (3.49)	3.8 (4.27)	0.2 (3.25)	3.0 (1.41)	6.0 (0.0)
Total Protein, Day85, n= 6,12,6,4,2	0.8 (3.54)	3.3 (5.03)	0.3 (4.97)	3.5 (3.42)	4.5 (2.12)
Total Protein, Day211, n= 6,12,6,4,2	2.5 (4.81)	5.1 (4.23)	1.7 (3.33)	8.0 (2.71)	4.5 (12.02)

Population analysed: Safety population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Primary outcome: Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate

Time frame: Outcome Measure Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211. Mean (Standard Deviation). Unit: Millimoles per liter

Measure	Cohort 1 GSK3228836 150 mg n = 6	Cohort 2 and Cohort 3 GSK3228836 300 mg n = 12	Cohorts 1-3 Placebo n = 6	Cohort 4 GSK3228836 300 mg n = 5	Cohort 4 Placebo n = 2
Bicarbonate, Day29, n= 6,12,6,4,2	0.3 (1.21)	0.2 (1.11)	1.0 (1.41)	0.0 (2.16)	-2.0 (2.83)
Bicarbonate, Day57, n= 5,12,6,4,2	1.0 (2.65)	-0.1 (2.02)	-0.2 (2.14)	0.3 (2.87)	-3.0 (2.83)
Bicarbonate, Day85, n= 6,12,6,4,2	0.2 (3.92)	0.5 (1.83)	-0.8 (0.75)	-0.8 (0.50)	-2.0 (2.83)
Bicarbonate, Day211, n= 6,12,6,4,2	2.8 (1.94)	-1.0 (1.81)	-0.8 (1.72)	-0.8 (2.22)	-2.0 (4.24)
Calcium, Day29, n= 6,12,6,4,2	0.012 (0.0811)	0.015 (0.0735)	-0.040 (0.0506)	0.063 (0.0479)	-0.030 (0.0707)
Calcium, Day57, n= 5,12,6,4,2	0.036 (0.0658)	0.029 (0.0899)	-0.038 (0.0471)	0.013 (0.0150)	0.010 (0.0566)
Calcium, Day85, n= 6,12,6,4,2	0.020 (0.0672)	0.046 (0.0944)	-0.028 (0.0679)	-0.013 (0.0675)	0.050 (0.0707)
Calcium, Day211, n= 6,12,6,4,2	0.052 (0.0618)	0.056 (0.0745)	-0.025 (0.0789)	0.068 (0.0746)	-0.025 (0.1344)

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Non-serious (>=5%) and serious adverse events were collected up to Day 211. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 GSK3228836 150 mg	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Cohort 2 and Cohort 3 GSK3228836 300 mg	1 of 12 (8.3%)	6 of 12 (50%)	0 of 12
Cohorts 1-3 Placebo	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Cohort 4 GSK3228836 300 mg	0 of 5 (0%)	3 of 5 (60%)	0 of 5
Cohort 4 Placebo	0 of 2 (0%)	0 of 2 (0%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42550463Delahaye JL, You S, Fu K, Van Buren S, Zhu C, Jordan W, Ray A, Freudenberg JM, Consalvo KM, Pagliaroli L, Joshi S, Dhawan P, Theodore D, Paff M, Walker J, Singh JM. Bepirovirsen induces innate immune proteins independent of HBV. Hepatol Int. 2026 Aug 4. doi: 10.1007/s12072-026-11134-z. Online ahead of print.
Derived from this study: PubMed 39950613Han K, Youssef AS, Magee M, Hood S, Tracey H, Kwoh J, Theodore D, Paff M, Nader A. Lack of Pharmacokinetic Drug-Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs. Clin Pharmacol Drug Dev. 2025 Apr;14(4):281-291. doi: 10.1002/cpdd.1518. Epub 2025 Feb 14.
Derived from this study: PubMed 34642494Yuen MF, Heo J, Jang JW, Yoon JH, Kweon YO, Park SJ, Tami Y, You S, Yates P, Tao Y, Cremer J, Campbell F, Elston R, Theodore D, Paff M, Bennett CF, Kwoh TJ. Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial. Nat Med. 2021 Oct;27(10):1725-1734. doi: 10.1038/s41591-021-01513-4. Epub 2021 Oct 12.

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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.

The record lists no contact. Use the official record to reach the sponsor.

7 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 IONIS-HBVRx in people with Hepatitis B and Chronic Hepatitis B Atypical, run by GlaxoSmithKline at 7 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 5 inclusion and 18 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 10 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in South Korea, Hong Kong. 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 21 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%) (time frame: Up to Day 211). The study lists 26 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02981602, which also lists 3 linked publications.

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 10 Aug 2021.