Hepatitis B
Conditions
Keywords
Bepirovirsen, Chronic hepatitis B, First-time-in-human, GSK3965193
Brief summary
This Phase 1/2a multiple part study is a first time-in-human (FTIH) study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single (Part 1) and repeat doses (Part 2) of GSK3965193 in healthy participants. Part 3 will evaluate the ability of GSK3965193 to lower hepatitis B virus surface antigen (HBsAg) in participants living with chronic hepatitis B infection (PLWCHB) and will be given the option to subsequently receive treatment with open label bepirovirsen. Part 4 will evaluate the safety and tolerability of combination therapy with GSK3965193 and bepirovirsen and the potential to effect sustained virologic response in PLWCHB.
Interventions
DRUGGSK3965193
GSK3965193 was administered
DRUGPlacebo to match GSK3965193
Placebo to match GSK3965193 was administered
DRUGBepirovirsen
Bepirovirsen was administered
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a double-blind study
Intervention model description
Parts 1 and Part 2B are crossover and Part 2A, Part 3 and Part 4 are parallel group
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Parts 1 and 2: Participants between 18 and 55 years of age inclusive, at the time of signing the informed consent. * Parts 3 and 4: Participants between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Body weight \>=50 kilograms (kg) and body mass index within the range 18-32 kilograms per square meter (kg/m\^2) (inclusive). * Male or female participant: a. Parts 1 and 2: woman of nonchildbearing potential only. b. Parts 3 and 4: woman of nonchildbearing potential or woman of child-bearing potential who is not pregnant or breastfeeding and is using a contraceptive method that is highly effective. * Capable of giving signed informed consent. * Additional Inclusion Criteria for PLWCHB (Parts 3 and 4). * Participants who have documented chronic hepatitis B virus (HBV) infection \>=6 months prior to screening. * Participants currently receiving stable NA therapy (e.g., tenofovir disoproxil, tenofovir alafenamide, entecavir). * Plasma or serum HBsAg concentration \>100 IU/mL. * Plasma or serum HBV deoxyribonucleic acid (DNA) concentration \<90 IU/mL. * Hepatitis B virus e-antigen (HBeAg) positive or negative. * Alanine aminotransferase (ALT) \<=2 times the upper limit of normal (ULN)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Treatment Emergent Adverse Events (STEAEs), and Treatment Withdrawals Due to TEAEs | From the start of study intervention (Day 1) up to 12 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date (i.e., Day 1) till Day 5 after study intervention administration. Any AE which started post Day 5 of study intervention administration was not considered as TEAE. |
| Part 2A: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs | From the start of study intervention (Day 1) up to 6 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date. |
| Part 2B: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs | From the start of study intervention (Day 1) up to 9 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date (i.e., Day 1) till Day 5 after study intervention administration. Any AE which started post Day 5 of study intervention administration was not considered as TEAE. |
| Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs | From the start of study intervention (Day 1) up to 6 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset or worsen date was on or after study intervention start date. Data for the placebo or GSK3965193 monotherapy phase were presented. |
| Part 4: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs | From the start of study intervention (Day 1) up to 48 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE would be considered treatment emergent if the AE onset or worsen date was on or after study intervention start date. |
| Part 1: Number of Participants With Clinically Significant Hematology and Clinical Chemistry Parameters | At Day 2 | Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, RBC indices (mean corpuscular volume \[MCV\] and mean corpuscular hemoglobin \[MCH\]), white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), blood urea nitrogen (BUN), creatinine, glucose (non-fasting), potassium, sodium, calcium, aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Clinical significance of laboratory parameters was determined by the investigator. |
| Part 2A: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters | Up to 21 days | Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator. |
| Part 2B: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters | Up to 9 weeks | Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator. |
| Part 3: Number of Participants With Clinically Significant Hematology and Clinical Chemistry Parameters | Up to 35 days | Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Clinical significance of laboratory parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented. |
| Part 3: Number of Participants With Clinically Significant Urinalysis Parameters | Up to 28 days | Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented. |
| Part 4: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters | Up to 48 weeks | Blood samples were planned to be collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were planned to be analyzed using automated urinalysis or urine dipstick. Microscopic examination was planned to be performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters would be determined by the investigator. |
| Part 1: Number of Participants With Clinically Significant Vital Sign Findings | Up to 12 weeks | Vital signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator. |
| Part 2A: Number of Participants With Clinically Significant Vital Sign Findings | Up to 21 days | Vital signs included SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator. |
| Part 2B: Number of Participants With Clinically Significant Vital Sign Findings | Up to 9 weeks | Vital signs included SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator. |
| Part 3: Number of Participants With Clinically Significant Vital Sign Findings | Up to 35 days | Vital signs included temperature, SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented. |
| Part 4: Number of Participants With Clinically Significant Vital Signs Findings | Up to 48 weeks | Vital signs were planned to include temperature, SBP and DBP, pulse and respiratory rate and were planned to be measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings would be determined by the investigator. |
| Part 1: Number of Participants With Clinically Significant Electrocardiogram [ECG] Findings | Up to 12 weeks | A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and corrected QT (QTc) intervals. Clinical significance of ECG parameters was determined by the investigator. |
| Part 2A: Number of Participants With Clinically Significant ECG Findings | Up to 21 days | A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG parameters was determined by the investigator. |
| Part 3: Number of Participants With Clinically Significant ECG Findings | Up to 35 days | A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented. |
| Part 4: Number of Participants With Clinically Significant ECG Findings | Up to 25 weeks | A 12-lead ECG was planned to be recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters planned to be collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG findings would be determined by the investigator. |
| Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 7 | Baseline and Day 7 | Sensory nerve conduction testing was performed to detect neuropathy in participants. Nerve conduction velocity (NCV) and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25 percent (%) decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 7 was reported. |
| Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 14 | Baseline and Day 14 | Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 14 was reported. |
| Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 42 | Baseline and Day 42 | Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 42 was reported. |
| Part 3: Number of Participants With Changes in Sensory Nerve Conduction at Day 15 | Baseline and Day 15 | Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. The best measurement out of Screening and Day -1 was considered as Baseline, best being the higher measurement. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 15 for the placebo or GSK3965193 monotherapy phase was reported. |
| Part 3: Number of Participants With Changes in Sensory Nerve Conduction at Day 29 | Baseline and Day 29 | Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. The best measurement out of Screening and Day -1 was considered as Baseline, best being the higher measurement. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 29 for the placebo or GSK3965193 monotherapy phase was reported. |
| Part 4: Number of Participants With Changes in Sensory Nerve Conduction | Baseline up to 29 days | Sensory nerve conduction testing was planned to be performed to detect neuropathy in participants. NCV and nerve conduction amplitude were planned to be determined. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from baseline was planned to be reported. |
| Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3965193 Following Single Dose Administration | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours (h) post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 2A: AUC Over the Dosing Interval Tau (AUC[0-tau]) of GSK3965193 Following Repeat Dose Administration | Pre-dose and 15 minutes (min), 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, and 12 h post-first dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. As the dosing interval Tau was 12 hours, AUC(0-tau) is the same as AUC from time zero to 12 hours after dosing (AUC\[0-12\]). |
| Part 1: Maximum Observed Concentration (Cmax) of GSK3965193 Following Single Dose Administration | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 2A: Cmax of GSK3965193 Following Repeat Dose Administration | Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3965193 Following Single Dose Administration | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 2A: Tmax of GSK3965193 Following Repeat Dose Administration | Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 1: Apparent Terminal Half-life (T1/2) of GSK3965193 Following Single Dose Administration | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 2A: T1/2 of GSK3965193 Following Repeat Dose Administration | Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 3: Maximum Reduction of Serum HBsAg Levels From Baseline | From Baseline (Pre-dose on Day 1) up to 6 weeks | Blood samples were collected from participants to assess HBsAg levels for the placebo or GSK3965193 monotherapy phase. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Posterior mean and associated 95 percent (%) credible interval were derived for maximum reduction of serum HBsAg levels from Baseline using Bayesian mixed model repeated measures. The data presented are mean referring to posterior mean, with 95% confidence interval referring to 95% credible interval. |
| Part 4: Number of Participants Achieving Complete Response | Up to 48 weeks | Blood samples were planned to be collected to assess HBsAg and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Complete response is defined HBsAg and HBV DNA below lower limit of quantification (LLOQ) for 6 consecutive months after the planned end of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2B: AUC(0-inf) of GSK3965193 Following Single Dose Administration | Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, and 72 h post-dose | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 2B: Cmax of GSK3965193 Following Single Dose Administration | Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, and 72 h post-dose | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 3: AUC(0-tau) of GSK3965193 Following Repeat Dose Administration | Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28 | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 3: Cmax of GSK3965193 Following Repeat Dose Administration | Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28 | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 3: Tmax of GSK3965193 Following Repeat Dose Administration | Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28 | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 3: T1/2 of GSK3965193 Following Repeat Dose Administration | Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28 | Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. |
| Part 3: Number of Participants With Greater Than or Equal to [≥] 0.5 Times Log International Units Per Milliliters [IU/mL] Reduction From Baseline in Serum HBsAg Levels | From Baseline (Day 1) up to 42 days | Blood samples were collected from participants at indicated time points to assess HBsAg levels. |
| Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs Among Participants Opting for Optional Bepirovirsen Treatment | From the start of study intervention up to 54 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. |
| Part 3: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters Among Participants Opting for Optional Bepirovirsen Treatment | From Week 7 up to 54 weeks | Blood samples were planned to be collected to analyze clinical chemistry and hematology parameters: hemoglobin, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, platelets, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells, reticulocytes, ALT, albumin, alkaline phosphatase, AST, bilirubin, calcium corrected for albumin, creatinine, glucose, potassium, and sodium. Urine samples were planned to be analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Number of participants with clinically significant clinical chemistry, hematology, and urinalysis parameters were reported. Clinical significance was determined by the investigator. |
| Part 3: Number of Participants With Clinically Significant Vital Signs Among Participants Opting for Optional Bepirovirsen Treatment | From Week 7 up to 54 weeks | Vital signs were planned to include temperature and were planned to be measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of vital signs was determined by the investigator. |
| Part 4: Number of Participants With HBsAg Loss | Up to 48 weeks | Blood samples were collected from participants at indicated time points to assess HBsAg levels. HBsAg loss is defined by two consecutive measurements of HBsAg below the LLOQ any time during the study (on-treatment and post-treatment). |
Countries
Canada, France, Italy, South Korea, Thailand, United Kingdom
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Recruitment details
The study was planned to be conducted in 4 parts. Part 1, a crossover study, consisted of 2 cohorts (Cohorts 1 and 2). Part 2 consisted of 2 sub-parts: Part 2A was a parallel group study comprised of 3 cohorts (Cohorts 3, 4, and 5); and Part 2B was a crossover study comprised of 1 cohort (Cohort 6). Part 3 was a parallel group study comprised of 1 cohort (Cohort 7). Part 4 was planned to be a parallel group study comprised of 1 cohort (Cohort 8).
Pre-assignment details
The study enrolled 74 participants (20 in Part 1, 23 in Part 2A, 13 in Part 2B, and 18 in Part 3). Part 2B was planned to have 3 treatment periods (TPs). However, TP3 was not conducted following safety and tolerability findings in TP2. The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4. Dose 1 (D1) was the lowest dose. Doses in ascending order are as follows: D1, D2, D3, D4, D9, D5, D10, D6, D7, and D8.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 18 to 55 years | 72 Participants |
| Age, Customized 56 to 65 years | 2 Participants |
| Race/Ethnicity, Customized ASIAN | 2 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 0 Participants |
| Race/Ethnicity, Customized WHITE | 0 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 4 | 0 / 11 | 0 / 13 | 0 / 4 | 0 / 14 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 2 / 16 | 3 / 6 | 1 / 6 | 1 / 6 | 1 / 6 | 3 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 4 / 6 | 6 / 6 | 4 / 7 | 4 / 4 | 3 / 11 | 1 / 13 | 2 / 4 | 4 / 14 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 16 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 4 | 0 / 11 | 0 / 13 | 0 / 4 | 0 / 14 | 0 / 0 | 0 / 0 |
Outcome results
None listed