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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis B Atypical; Hepatitis B

Treatments: Drug: IONIS-HBVRx; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02981602

205695

ISIS 505358-CS3 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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:

  1. Liver biopsy (i.e., Metavir Score F4) within 2 years of Screening, or
  2. Fibroscan > 12 KPa, within 12 months of Screening, or
  3. 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])

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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31 participants in 2 patient groups, including a placebo group

IONIS-HBVRx

Experimental group

Description:

Ascending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection

Treatment:

Drug: IONIS-HBVRx

Placebo

Placebo Comparator group

Description:

Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator

Treatment:

Drug: Placebo