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IONIS-HBVRx

Phase 2

Hepatitis B | Small molecule | Infectious Disease |GSK plc|Last Updated: Aug 10, 2021

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment31
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02981602Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV InfectionPHASE2 COMPLETED 31Feb 24, 2017Dec 26, 2019Aug 10, 20217 Hong Kong, South Korea
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Study Endpoints
Primary Endpoints
Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.

Secondary Endpoints
Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Day 29
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
Baseline (Day 1 pre-dose) and Week 31
Change From Baseline in HBV Surface Antigen (HBsAg) Level in Serum at Day 29
Baseline (Day 1 pre-dose) and Day 29
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
IONIS-HBVRxEXPERIMENTALAscending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection
PlaceboPLACEBO_COMPARATORSterile Normal Saline (0.9% NaCl) calculated volume to match active comparator
Interventions
NameTypeDescription
IONIS-HBVRxDRUGAscending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection
PlaceboDRUGPlacebo
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Eligibility Criteria
Age Range18 Years — 70 Years
SexALL
Healthy VolunteersNo
Study Sites7

Inclusion Criteria: * 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 ana...

Countries:Hong KongSouth Korea
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