Safety and Efficacy of HEPLISAV™ Hepatitis B Virus Vaccine Compared With Engerix-B® Vaccine

Condition(s) targeted: Hepatitis B

Intervention: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen (Biological); Hepatitis B Vaccine (Recombinant) (Biological)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Dynavax Technologies Corporation

Official(s) and/or principal investigator(s):
Eduardo B. Martins, MD, DPhil, Study Director, Affiliation: Dynavax Technologies Corporation

The purpose of this study is to find out if a new investigational hepatitis B virus vaccine, HEPLISAV™, is safe and effective compared with Engerix-B® vaccine in subjects 11-55 years old. The primary hypothesis is that the seroprotective immune response of HEPLISAV™ is at least as good as that of Engerix-B®.

Official title: A Phase III Safety and Efficacy Study to Compare Immune Responses Following Injection With Either Two Doses of HEPLISAV™ or Three Doses of Engerix-B®

Study design: Prevention, Randomized, Single Blind (Subject), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Portion of subjects who have a seroprotective immune response (anti-HBsAg ≥ 10 mIU/ml) after the final active injection in each treatment group (Week 12 for HEPLISAV™ and Week 28 for Engerix-B®)

Secondary outcome: Rates of adverse events and local and systemic reactions to injections

Detailed description: Infection with hepatitis B virus (HBV) is a major global health problem. Worldwide, it is estimated that 2 billion people have been infected previously and 350 million are chronically infected. While acute HBV infection is associated with significant illness, the risk of chronic infection is of great importance since 5-10% of infected adults will not clear the infection after the initial phase of the illness. About 25% of people who do not initially clear the infection will later develop chronic active hepatitis.

This study will evaluate the safety and efficacy of two injections of HEPLISAV™, compared with three injections of a commercially available HBV vaccine, Engerix-B®, in subjects 11 to 55 years old. About 1,740 subjects will be included in the study. Once subjects have been consented, screened, and randomized to treatment, all subjects will receive a total of three injections over a 24-week period, with a follow-up visit at 28 weeks. Subjects randomized to Engerix-B® will receive 3 injections of active vaccine, while subjects randomized to HEPLISAV™ will receive 2 injections of active vaccine plus 1 injection of placebo. Safety and tolerability will be evaluated by occurrence of adverse events, periodic laboratory tests, vital signs, and local/systemic reactogenicity.

Comparison: Subjects will receive treatment with either HEPLISAV™ or the comparator vaccine, Engerix-B®.

Minimum age: 11 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Willing and able to give written informed consent

- Is serum negative for HBV antibodies

Exclusion Criteria:

- Women who are pregnant or breastfeeding

- Any previous HBV infection

- Previous vaccination with any HBV vaccine (1 or more doses)

- Any autoimmune disease

- Received any blood products or antibodies within 3 months prior to study entry

- Ever received an injection with DNA plasmids or oligonucleotides

- Received any vaccines within 4 weeks prior to study entry

- Received any other investigational medicinal agent within 4 weeks prior to study

entry

Capital Health - Edmonton, Edmonton, Alberta T5N 4A3, Canada

Tasc Research Services, Inc., Surrey, British Columbia V3R 8P8, Canada

University of Manitoba, Manitoba Institute of Child Health, Winnipeg, Manitoba R3E 3P4, Canada

White Hills Medical Clinic, St. John's, Newfoundland and Labrador A1A 3R5, Canada

Commonwealth Medical Clinic, Mount Pearl, Newfoundland and Labrador A1N 1W7, Canada

Clinical Trials Research Centre, IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada

Ottawa Hospital, General Campus, Ottawa, Ontario K1H 8L6, Canada

Herridge Clinic, Ottawa, Ontario K1S 0G8, Canada

Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada

Manna Research, Toronto, Ontario M9W 4L6, Canada

Sarnia Institute of Clinical Research, Sarnia, Ontario N7T 4X3, Canada

Parkdale Medical Center (Extension), Charlottetown, Prince Edward Island C1A 5Y9, Canada

Centre Hospitalier Universitaire de Québec, Québec, Quebec G1E 7G9, Canada

McGill University Health Center, Pierrefonds, Quebec H9H 4Y6, Canada

Dynavax Webpage

Starting date: December 2006
Ending date: March 2008
Last updated: January 18, 2008