Phase 2
Completed N=31
Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV Infection
Hepatitis B · Chronic Hepatitis B Atypical
Source: ClinicalTrials.gov NCT02981602 ↗
Enrolled (actual)
31
Serious AEs
3.2%
Results posted
Dec 2020
Primary outcomePrimary: Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%) — 5; 6; 2; 3 Participants
Summary
To examine the safety and tolerability of IONIS-HBVRx administration to treatment-naive patients with chronic hepatitis B virus infection
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%) |
5; 6; 2; 3; 0; 0 | — |
| PRIMARY 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 |
15.7; 52.5; -0.7; 45.3; -0.5; 45.6 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time |
-0.8; 0.3; -1.3; 3.0; 1.5; 0.6 | — |
| PRIMARY Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate |
0.3; 0.2; 1.0; 0.0; -2.0; 1.0 | — |
| PRIMARY Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine |
-1.72; -1.07; -1.92; -1.53; 1.40; -2.14 | — |
| PRIMARY Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets |
0.00; 0.01; 0.00; 0.0; 0.0; 0.00 | — |
| PRIMARY Change From Baseline for Hematology Parameters: Hemoglobin |
-7.3; -6.8; -11.3; -6.0; -11.5; -3.3 | — |
| PRIMARY Change From Baseline for Hematology Parameter: Hematocrit |
-2.47; -2.39; -4.20; -2.23; -3.30; -1.17 | — |
| PRIMARY Change From Baseline Values in Urine Specific Gravity |
-0.0017; 0.0033; 0.0032; 0.0028; 0.0080; 0.0000 | — |
| PRIMARY Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio |
-3.340; -10.580; -3.480; 0.080; 0.006; -0.002 | — |
| PRIMARY Change From Baseline Values in Urine Protein |
-1.08; 7.06; -0.51; 11.13; 3.76; -2.57 | — |
| PRIMARY Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time |
-2.44; -2.33; -1.63; -0.45; 0.65; 1.23 | — |
| PRIMARY Change From Baseline Values in Blood Coagulation Factor: Prothrombin International Normalized Ratio |
-0.04; -0.04; 0.02; 0.03; 0.00; -0.02 | — |
| PRIMARY Change in Complement C3 Level at Worst Case Post Baseline Relative to Baseline |
-19.8; -22.3; -16.5; -12.4; -25.5 | — |
| PRIMARY Change in Complement C5a Level at Worst Case Post Baseline Relative to Baseline |
1.552; 3.778; 1.303; 2.232; 0.800 | — |
| PRIMARY Change in Complement Bb Level at Worst Case Post Baseline Relative to Baseline |
0.355; 0.365; 0.240; 0.472; 0.320 | — |
| PRIMARY Number of Participants With Reported Pregnancy |
0; 0; 0; 0; 0 | — |
| PRIMARY Change From Baseline in Body Temperature |
-0.05; -0.09; -0.15; 0.08; 0.30; 0.03 | — |
| PRIMARY Change From Baseline in Body Weight |
-0.48; 0.20; 0.52; 0.00; -1.25; -0.40 | — |
| PRIMARY Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure |
-6.3; -8.8; -9.2; -3.0; 0.5; 3.7 | — |
| PRIMARY Change From Baseline in Respiratory Rate |
0.3; 0.7; 0.3; -0.8; -2.5; -0.5 | — |
| PRIMARY Change From Baseline in Pulse Rate |
-4.7; 4.3; 1.5; 9.0; 1.0; -1.5 | — |
| PRIMARY Number of Participants With Abnormal Findings in Physical Examination |
3; 1; 1; 0; 0 | — |
| PRIMARY Number of Participants Who Received Atleast One Concomitant Medication |
4; 8; 5; 5; 2 | — |
| PRIMARY Change From Baseline in Electrocardiogram Mean Ventricular Rate |
4.3; 5.6; 4.5; 8.2; 10.0; 1.8 | — |
| PRIMARY Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula |
-1.2; 1.8; 3.5; 0.8; 7.0; -1.7 | — |
| SECONDARY Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Day 29 |
-0.384; -1.655; -0.001; 0.075; 0.000 | 0.116 |
| SECONDARY Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Week 31 |
-4.754; -4.770; -3.547; 0.000; 0.000 | 0.609 |
| SECONDARY Change From Baseline in HBV Surface Antigen (HBsAg) Level in Serum at Day 29 |
-0.504; -1.556; 0.000; -1.986; -0.008 | 0.245 |
| SECONDARY Change From Baseline in HBsAg Level in Serum at Week 31 |
-0.523; -0.547; 0.059; -1.519; -0.043 | 0.141 |
| SECONDARY Percentage of Participants Who Achieved HBsAg Loss at Day 29 and Week 31 |
0; 16.7; 0; 20.0; 0; 0 | — |
| SECONDARY Percentage of Participants Who Achieved HBV e Antigen (HBeAg) Loss at Day 29 and Week 31 Who Were HBeAg Positive at Baseline |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Change From Baseline in Serum HBeAg Concentration at Day 29 in Participants Who Were HBeAg Positive at Baseline |
-0.004; -0.052; 0.133 | 0.763 |
| SECONDARY Change From Baseline in Serum HBeAg Concentration at Week 31 in Participants Who Were HBeAg Positive at Baseline |
-0.577; -0.195; 0.131 | 0.372 |
| SECONDARY Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection |
0.00; 0.00; 0.00; 1187.00; 2145.58; 1630.00 | — |
Eligibility Criteria
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 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
Exclusion Criteria
- 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
- 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])
Data sourced from ClinicalTrials.gov (NCT02981602). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.