Safety and Immunogenicity Study of the Hepatitis B Vaccine, HEPLISAV™, Compared to Engerix-B® Vaccine

• ClinicalTrials.gov Identifier: NCT02117934
• Recruitment Status: Completed
• First Posted: April 21, 2014
• Results First Posted: January 10, 2018
• Last Update Posted: March 20, 2019
• Sponsor: Dynavax Technologies Corporation
• Information provided by (Responsible Party): Dynavax Technologies Corporation

Tracking Information

• First Submitted Date: April 15, 2014
• First Posted Date: April 21, 2014
• Results First Submitted Date: December 8, 2017
• Results First Posted Date: January 10, 2018
• Last Update Posted Date: March 20, 2019
• Study Start Date: April 2014
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 15, 2018)

• Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest [ Time Frame: Week 56 ]
  The percentage of participants with Medically-attended adverse events (MAEs), Serious Adverse Events (SAEs), and immune-mediated Adverse Events of Special Interest (AESIs). MAEs are Adverse events (AEs) for which a subject sought medical attention at a doctor's office, clinic or study site, or emergency room, or was hospitalized. SAEs are AEs that met the definition of Serious per FDA regulations. Immune-mediated AESIs are AEs that were confirmed to be autoimmune in etiology.
• Percentage of Subjects With Type 2 Diabetes Mellitus Who Have a Seroprotective Immune Response [ Time Frame: Week 28 ]
  Percentage of subjects with type 2 diabetes mellitus who have a seroprotective immune response (anti-HBs ≥ 10 milli-international unit (mIU)/mL) who receive HEPLISAV compared with subjects who receive Engerix-B

Original Primary Outcome Measures (submitted: April 17, 2014)

• Proportion of subjects reporting clinically significant adverse events [ Time Frame: 12 months after last dose of HEPLISAV (Week 56) ]
• Proportion of subjects with type 2 diabetes mellitus with seroprotective immune response (anti-HBs ≥ 10 mIU/mL) who receive HEPLISAV compared with subjects who receive Engerix-B [ Time Frame: Week 28 ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Immunogenicity Study of the Hepatitis B Vaccine, HEPLISAV™, Compared to Engerix-B® Vaccine
• Official Title: A Phase 3, Observer-Blinded, Randomized, Active-Controlled (Engerix-B), Multicenter Trial of the Safety and Immunogenicity of HEPLISAV in Adults 18 to 70 Years of Age
• Brief Summary: The purpose of the study is to evaluate the safety and immunogenicity of an investigational hepatitis B vaccine (HEPLISAV) in adults 18 to 70 years of age.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Healthy

Intervention

• Biological: HEPLISAV
  Intramuscular injections at Week 0 and Week 4, plus a placebo injection at Week 24
  Other Names:

  • Hepatitis B vaccine (recombinant), adjuvanted
  • HEPLISAV-B
• Biological: Engerix-B
  Intramuscular injections at Week 0, Week 4, and Week 24
  Other Name: Hepatitis B vaccine (recombinant)

Study Arms

• Experimental: HEPLISAV
  0.5 mL HEPLISAV (20 mcg HBsAg and 3000 mcg 1018) administered intramuscularly in the deltoid muscle at Weeks 0, 4, and placebo (saline injection) at Week 24, followed by a 52-week safety follow-up from the last active dose of HEPLISAV.
  Intervention: Biological: HEPLISAV
• Active Comparator: Engerix-B
  1.0 mL Engerix-B (20 mcg HBsAg adsorbed on 500 mcg of aluminum hydroxide) administered intramuscularly in the deltoid muscle at Weeks 0, 4, and 24, followed by a 32-week safety follow-up from the last dose of Engerix-B.
  Intervention: Biological: Engerix-B

Publications *

• Hyer RN, Janssen RS. Immunogenicity and safety of a 2-dose hepatitis B vaccine, HBsAg/CpG 1018, in persons with diabetes mellitus aged 60-70 years. Vaccine. 2019 Sep 16;37(39):5854-5861. doi: 10.1016/j.vaccine.2019.08.005. Epub 2019 Aug 17.
• Jackson S, Lentino J, Kopp J, Murray L, Ellison W, Rhee M, Shockey G, Akella L, Erby K, Heyward WL, Janssen RS; HBV-23 Study Group. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018 Jan 29;36(5):668-674. doi: 10.1016/j.vaccine.2017.12.038. Epub 2017 Dec 27.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 26, 2016): 8374
• Original Estimated Enrollment (submitted: April 17, 2014): 8250
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

A subject must meet all of the following criteria to be eligible for the trial:

Inclusion Criteria:

• Be 18-70 years of age, inclusive
• Able to comprehend and follow all required study procedures and be available for all visits scheduled in the study
• If a woman is of childbearing potential, she must consistently use an acceptable method of contraception or confirm in writing she will abstain from sexual activity from the Screening Visit through Week 28.
• Able and willing to provide informed consent

A subject with any one of the following criteria is not eligible for the trial:

Exclusion Criteria:

• Previous receipt of any hepatitis B vaccine
• History of hepatitis B or human immunodeficiency virus (HIV) infection or positive test for HBsAg, anti-HBs, antibody to hepatitis B core antigen (anti-HBc), or antibody to HIV
• History of autoimmune disorder
• History of sensitivity to any component of study vaccines

• Has received the following prior to the first injection:

  1. Within 28 days:

     • Any vaccine
     • Systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immune suppressive medication
     • Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF)
     • Any other investigational medicinal agent
  2. Within 90 days: Blood products or immunoglobulin
  3. At any time: An injection of DNA plasmids or oligonucleotide
• If female: Pregnant, nursing, or planning to become pregnant during the trial
• Is undergoing chemotherapy or expected to receive chemotherapy during the study period; has a diagnosis of cancer within the last 5 years other than squamous or basal cell carcinoma of the skin
• Any other medical condition considered by the investigator likely to interfere with the subject's compliance or the interpretation of study assessments

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02117934
• Other Study ID Numbers: DV2-HBV-23
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Dynavax Technologies Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Dynavax Technologies Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Robert Janssen, MD; Dynavax Technologies Corporation

• PRS Account: Dynavax Technologies Corporation
• Verification Date: March 2019