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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2016 by Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc. Identifier:
First received: December 1, 2016
Last updated: December 2, 2016
Last verified: December 2016
To examine the safety and tolerability of IONIS-HBVRx administration to treatment-naive patients with chronic hepatitis B virus infection

Condition Intervention Phase
Chronic Hepatitis B Atypical
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Ionis Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Safety and tolerability of multiple doses of IONIS-HBVRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters) [ Time Frame: 26 Weeks ] [ Designated as safety issue: Yes ]
    The safety and tolerability of IONIS-HBVRx will be assessed by determining the incidence, severity, and dose relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with ISIS 505358 will be compared with those from subjects dosed with placebo.

Secondary Outcome Measures:
  • Plasma HBV DNA Concentration [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    IONIS-HBVRx will be compared with those from subjects dosed with placebo.

Estimated Enrollment: 24
Study Start Date: December 2016
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IONIS-HBVRx
Ascending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection
Ascending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection
Other Name: ISIS 505358
Placebo Comparator: Placebo
Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator
Drug: Placebo

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.

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  • Serum HBsAg ≥ 50 IU/mL

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
  • 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])
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02981602

Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
Study Director: Vincent Lopez PPD
  More Information

Responsible Party: Ionis Pharmaceuticals, Inc. Identifier: NCT02981602     History of Changes
Other Study ID Numbers: ISIS 505358-CS3 
Study First Received: December 1, 2016
Last Updated: December 2, 2016
Health Authority: Hong Kong: Department of Health
Korea: Food and Drug Administration
United States: Food and Drug Administration

Keywords provided by Ionis Pharmaceuticals, Inc.:

Additional relevant MeSH terms:
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Antiviral Agents
Anti-Infective Agents processed this record on December 07, 2016