Dose Ranging Safety and Efficacy of Therapeutic HSV-2 Vaccine

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Genocea Biosciences, Inc.
Sponsor:
Information provided by (Responsible Party):
Genocea Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT02114060
First received: April 11, 2014
Last updated: October 17, 2014
Last verified: October 2014
  Purpose

This is a randomized, double-blind, factorial study to compare the reduction in viral shedding among 6 different combinations of GEN-003, a therapeutic HSV-2 vaccine and Matrix-M2 adjuvant.

Secondary objectives of the study include:

  • Evaluation of the safety and tolerability of GEN-003 in combination with Matrix-M2 compared to placebo.
  • Comparison of the impact on clinical Herpes Simplex Virus type-2 (HSV-2) disease among the 6 different combinations of GEN-003 antigens and Matrix-M2 adjuvant measured by:

    • Time to first clinical and/or virologic recurrence,
    • Proportion of subjects who are recurrence free at 6 and 12 months after the last dose of vaccine,
    • Lesion rate (percent of days with genital lesions present) during the post-vaccination swabbing periods.
  • Evaluation of cellular and humoral responses to GEN-003 antigens.

Additional objectives include:

  • Assessment of the correlation between immune responses and change in viral shedding or impact on clinical disease as defined above.
  • Determination of the recurrence rate in a subset of subjects not receiving suppressive antivirals throughout the study.

Eligible subjects will enter a baseline period to collect anogenital swabs for 28 consecutive days prior to randomization. Each subject will receive up to 3 doses at 21 day intervals. Subjects will be followed for safety and immunologic response for 12 months following their last dose.


Condition Intervention Phase
Genital Herpes Simplex Type 2
Biological: Matrix-M2 Adjuvant
Biological: GEN-003 Vaccine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Factorial Study to Compare the Safety and Efficacy of Varying Combinations of GEN-003 and Matrix-M2 in Subjects With Genital HSV-2 Infection

Resource links provided by NLM:


Further study details as provided by Genocea Biosciences, Inc.:

Primary Outcome Measures:
  • Change in proportion of days with detectable viral shedding [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immunogenicity measured by humoral (antibody) and T-cell responses to vaccine antigens [ Time Frame: 33 weeks ] [ Designated as safety issue: No ]
  • Impact on clinical HSV-2 disease based on time to recurrence and lesion rate [ Time Frame: 53 weeks ] [ Designated as safety issue: No ]
  • Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: 57 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 315
Study Start Date: July 2014
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GEN-003 30μg / Matrix-M 25μg
GEN-003/M2: GEN-003 (30 μg of each antigen) with Matrix-M2 adjuvant (25 μg), administered as a 0.5 mL intramuscular (IM) injection.
Biological: Matrix-M2 Adjuvant

Matrix-M2 adjuvant (25, 50 or 75 μg), administered in combination with GEN-003 vaccine as a 0.5 mL intramuscular (IM) injection.

Matrix-M2 is made up of immune stimulating complexes derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol. Quillaja saponins are surface-active substances derived from the tree Quillaja saponaria Molina.

Other Names:
  • Matrix-M2 Adjuvant
  • Matrix M2
  • Matrix M
  • Matrix-M
Biological: GEN-003 Vaccine

GEN-003 Vaccine (30 or 60μg of each antigen) in combination with Matrix-M2 Adjuvant, administered as a 0.5mL intramuscular injection

GEN-003 is a HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens:

  • GB208: a T cell antigen and internal fragment of the immediate early (IE) protein ICP4.
  • GB217: a B cell antigen (also known as glycoprotein D, or gD)
Other Names:
  • GEN-003 Vaccine
  • HSV Vaccine
Experimental: GEN-003 30μg / Matrix-M2 50μg
GEN-003/M2: GEN-003 (30 μg of each antigen) with Matrix-M2 adjuvant (50 μg), administered as a 0.5 mL intramuscular (IM) injection.
Biological: Matrix-M2 Adjuvant

Matrix-M2 adjuvant (25, 50 or 75 μg), administered in combination with GEN-003 vaccine as a 0.5 mL intramuscular (IM) injection.

Matrix-M2 is made up of immune stimulating complexes derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol. Quillaja saponins are surface-active substances derived from the tree Quillaja saponaria Molina.

Other Names:
  • Matrix-M2 Adjuvant
  • Matrix M2
  • Matrix M
  • Matrix-M
Biological: GEN-003 Vaccine

GEN-003 Vaccine (30 or 60μg of each antigen) in combination with Matrix-M2 Adjuvant, administered as a 0.5mL intramuscular injection

GEN-003 is a HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens:

  • GB208: a T cell antigen and internal fragment of the immediate early (IE) protein ICP4.
  • GB217: a B cell antigen (also known as glycoprotein D, or gD)
Other Names:
  • GEN-003 Vaccine
  • HSV Vaccine
Experimental: GEN-003 30μg / Matrix-M2 75μg
GEN-003/M2: GEN-003 (30 μg of each antigen) with Matrix-M2 adjuvant (75 μg), administered as a 0.5 mL intramuscular (IM) injection.
Biological: Matrix-M2 Adjuvant

Matrix-M2 adjuvant (25, 50 or 75 μg), administered in combination with GEN-003 vaccine as a 0.5 mL intramuscular (IM) injection.

Matrix-M2 is made up of immune stimulating complexes derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol. Quillaja saponins are surface-active substances derived from the tree Quillaja saponaria Molina.

Other Names:
  • Matrix-M2 Adjuvant
  • Matrix M2
  • Matrix M
  • Matrix-M
Biological: GEN-003 Vaccine

GEN-003 Vaccine (30 or 60μg of each antigen) in combination with Matrix-M2 Adjuvant, administered as a 0.5mL intramuscular injection

GEN-003 is a HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens:

  • GB208: a T cell antigen and internal fragment of the immediate early (IE) protein ICP4.
  • GB217: a B cell antigen (also known as glycoprotein D, or gD)
Other Names:
  • GEN-003 Vaccine
  • HSV Vaccine
Experimental: GEN-003 60μg / Matrix-M2 25μg
GEN-003/M2: GEN-003 (60 μg of each antigen) with Matrix-M2 adjuvant (25 μg), administered as a 0.5 mL intramuscular (IM) injection.
Biological: Matrix-M2 Adjuvant

Matrix-M2 adjuvant (25, 50 or 75 μg), administered in combination with GEN-003 vaccine as a 0.5 mL intramuscular (IM) injection.

Matrix-M2 is made up of immune stimulating complexes derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol. Quillaja saponins are surface-active substances derived from the tree Quillaja saponaria Molina.

Other Names:
  • Matrix-M2 Adjuvant
  • Matrix M2
  • Matrix M
  • Matrix-M
Biological: GEN-003 Vaccine

GEN-003 Vaccine (30 or 60μg of each antigen) in combination with Matrix-M2 Adjuvant, administered as a 0.5mL intramuscular injection

GEN-003 is a HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens:

  • GB208: a T cell antigen and internal fragment of the immediate early (IE) protein ICP4.
  • GB217: a B cell antigen (also known as glycoprotein D, or gD)
Other Names:
  • GEN-003 Vaccine
  • HSV Vaccine
Experimental: GEN-003 60μg / Matrix-M2 50μg
GEN-003/M2: GEN-003 (60 μg of each antigen) with Matrix-M2 adjuvant (50 μg), administered as a 0.5 mL intramuscular (IM) injection.
Biological: Matrix-M2 Adjuvant

Matrix-M2 adjuvant (25, 50 or 75 μg), administered in combination with GEN-003 vaccine as a 0.5 mL intramuscular (IM) injection.

Matrix-M2 is made up of immune stimulating complexes derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol. Quillaja saponins are surface-active substances derived from the tree Quillaja saponaria Molina.

Other Names:
  • Matrix-M2 Adjuvant
  • Matrix M2
  • Matrix M
  • Matrix-M
Biological: GEN-003 Vaccine

GEN-003 Vaccine (30 or 60μg of each antigen) in combination with Matrix-M2 Adjuvant, administered as a 0.5mL intramuscular injection

GEN-003 is a HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens:

  • GB208: a T cell antigen and internal fragment of the immediate early (IE) protein ICP4.
  • GB217: a B cell antigen (also known as glycoprotein D, or gD)
Other Names:
  • GEN-003 Vaccine
  • HSV Vaccine
Experimental: GEN-003 60μg / Matrix-M2 75μg
GEN-003/M2: GEN-003 (60 μg of each antigen) with Matrix-M2 adjuvant (75 μg), administered as a 0.5 mL intramuscular (IM) injection.
Biological: Matrix-M2 Adjuvant

Matrix-M2 adjuvant (25, 50 or 75 μg), administered in combination with GEN-003 vaccine as a 0.5 mL intramuscular (IM) injection.

Matrix-M2 is made up of immune stimulating complexes derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol. Quillaja saponins are surface-active substances derived from the tree Quillaja saponaria Molina.

Other Names:
  • Matrix-M2 Adjuvant
  • Matrix M2
  • Matrix M
  • Matrix-M
Biological: GEN-003 Vaccine

GEN-003 Vaccine (30 or 60μg of each antigen) in combination with Matrix-M2 Adjuvant, administered as a 0.5mL intramuscular injection

GEN-003 is a HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens:

  • GB208: a T cell antigen and internal fragment of the immediate early (IE) protein ICP4.
  • GB217: a B cell antigen (also known as glycoprotein D, or gD)
Other Names:
  • GEN-003 Vaccine
  • HSV Vaccine
Placebo Comparator: Placebo
0.9% Normal Saline administered as a 0.5 mL intramuscular (IM) injection.
Drug: Placebo
Other Names:
  • 0.9% Normal Saline
  • NaCl
  • Saline
  • Normal Saline

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and non-pregnant females, ages 18 to 50 years inclusive.
  • Diagnosis of genital HSV-2 infection for > 1 year supported by ONE of the following documented in the medical history or performed at screening:

    • Western blot for HSV-2
    • Type-specific polymerase chain reaction (PCR) or viral culture
    • Compatible clinical history AND
  • Positive HerpeSelect® 2 Enzyme-linked Immunosorbent Assay (ELISA) Immunoglobulin G (IgG) with an index value >3.5, or
  • Positive LIAISON® HSV-2 Type-Specific IgG
  • A history of at least 3 and no more than 9 reported clinical occurrences in the prior 12 months, or, if currently on suppressive therapy, history of at least 3 and no more than 9 reported clinical occurrences in the 12 months prior to initiation of suppressive therapy.
  • Collection of at least 45 of 56 anogenital swabs during the baseline period.
  • Willing and able to provide written informed consent.
  • Willing to perform and comply with all study procedures including attending clinic visits as scheduled.
  • Men and women of childbearing potential, must be willing to practice a highly effective method of contraception that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, vasectomy, licensed hormonal methods, intrauterine device (IUD), or barrier method (e.g., condom, diaphragm) for 28 days before and 90 days after receiving Study Drug.

Exclusion Criteria:

  • On suppressive antiviral medication within 7 days of beginning baseline anogenital swab collection period.
  • History of genital Herpes Simplex Virus type-1 (HSV-1) infection.
  • History of any form of ocular Herpes Simplex Virus (HSV) infection, HSV-related erythema multiforme, or herpes meningitis or encephalitis.
  • Immunocompromised individuals, including those receiving immunosuppressive doses of corticosteroids (more than 20 mg of prednisone given daily or on alternative days for 2 weeks or more within 6 months prior to the first dose of Study Drug, any dose of corticosteroids within 30 days of the first dose of Study Drug, or high dose inhaled corticosteroids [> 960 μg/day of beclomethasone dipropionate or equivalent]) or other immunosuppressive agents.
  • Presence or history of autoimmune disease, regardless of current treatment.
  • Positive serologic test for Human Immunodeficiency Virus (HIV-1) or hepatitis C infection; positive hepatitis B surface antigen (HBsAg).
  • Clinically significant laboratory abnormality or a value ≥ Grade 2.
  • Prior immunization with a vaccine containing HSV-2 antigens.
  • History of hypersensitivity to any component of the vaccine.
  • Receipt of any investigational drug within 30 days prior to the first dose of Study Drug.
  • Receipt of blood products within 90 days prior to the first dose of Study Drug.
  • Receipt of a live vaccine within 28 days prior to or a subunit vaccine within 14 days prior to the first dose of Study Drug or planned vaccination within 30 days following the last dose of Study Drug.
  • Pregnant or nursing women.
  • History of drug or alcohol abuse that, in the opinion of the Investigator, would interfere with the patient's ability to comply with the requirements of the study.
  • Other active, uncontrolled co-morbidities that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the study requirements.

NOTE: Subjects who are taking a medication to control an underlying co-morbidity may be enrolled if there have been no changes to their medication within 60 days prior to the first dose of Study Drug.

  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 ClinicalTrials.gov identifier: NCT02114060

Locations
United States, Alabama
University of Alabama Vaccine Research Unit Recruiting
Birmingham, Alabama, United States, 35294-0006
Contact: Catrena Johnson, RN, BSN, MPH    205-975-2842    catrena@uab.edu   
Contact: Pamela Cunningham, RN, BSN, MPH    205-975-2841    pelliott@uab.edu   
Principal Investigator: Nicholas Van Wagoner, MD, PhD         
United States, California
Medical Center for Clinical Research Recruiting
San Diego, California, United States, 92108
Contact: Kim Kerr    619-521-2841    kkerr@mccresearch.com   
Principal Investigator: William Koltun, MD         
Quest Clinical Research Recruiting
San Francisco, California, United States, 94115
Contact: Laura Holland    415-353-0212    laura@questclinical.com   
Contact: Kyle Eberly    415-353-0800    kyle@questclinical.com   
Principal Investigator: Jay Lalezari         
United States, Illinois
University of Illinois Department of Medicine Recruiting
Chicago, Illinois, United States, 60612
Contact: Regina Harden, BA    312-996-9565    ginaha@uic.edu   
Principal Investigator: Richard Novak, MD         
United States, Indiana
Indiana University Infectious Disease Research Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Elisha Largent    317-278-1614    elargent@iu.edu   
Contact: Paula Johnson    317-274-8473    johnpaul@iu.edu   
Principal Investigator: Kenneth Fife, MD, PhD         
United States, Massachusetts
The Fenway Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Ian Lemieux, RN, MPH    617-927-6027    ilemieux@fenwayhealth.org   
Principal Investigator: Lori Panther, MD, MPH         
United States, North Carolina
UNC Global HIV Prevention and Treatment Clinical Trials Unit Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Susan Blevins    919-843-8763    suzanne_blevins@med.unc.edu   
Contact: Erinn Hoffman    919-843-0720    Erin_Stephenson@med.unc.edu   
Principal Investigator: Peter Leone         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Tara Foltz, R.N., CCRC    513-636-7699    gambleprogram@cchmc.org   
Contact: Amy Cline, RN    513-636-7699    gambleprogram@cchmc.org   
Principal Investigator: David Bernstein, MD         
United States, Oregon
Westover Heights Clinic Recruiting
Portland, Oregon, United States, 97210
Contact: Rene Bernert    503-226-6678    rene@westoverheights.com   
Contact: Annie Kempa, CCRC    503-226-6678    annie@westoverheights.com   
Principal Investigator: Terri Warren, RN, ANP         
United States, Pennsylvania
Magee-Womens Hospital of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Ingrid Macio, PA-C    412-641-5455    imacio@mail.magee.edu   
Contact    412-641-4242      
Principal Investigator: Richard Beigi, MD         
United States, South Carolina
MUSC Womens Health Recruiting
Charleston, South Carolina, United States, 29425
Contact: Kenreka Yeadon-Osaboma    843-792-6323    yeadon@musc.edu   
Principal Investigator: David Soper         
United States, Texas
Tekton Research Recruiting
Austin, Texas, United States, 98745
Contact: Lauri Befus    512-388-5717    lbefus@tektonresearch.com   
Contact: Linda Salas    512-388-5717    lsalas@tektonresearch.com   
Principal Investigator: Gregg Lucksinger         
Center for Clinical Studies - Houston Recruiting
Houston, Texas, United States, 77030
Contact: Jesse Villanueva    713-528-8818    jvillanueva@ccstexas.com   
Principal Investigator: Stephen K Tyring, MD         
Center for Clinical Studies Recruiting
Houston, Texas, United States, 77065
Contact: Anant Patel    713-554-4688    apatel@ccstexas.com   
Principal Investigator: Lauren Campbell         
Center for Clinical Studies - Clear Lake/Webster Recruiting
Webster, Texas, United States, 77598
Contact: Deborah Yetman, BSN, RN    281-333-2288    dyetman@ccstexas.com   
Contact: Raul Laureano    281-333-2288    rlaureano@ccstexas.com   
Principal Investigator: Patricia C Lee, MD         
United States, Utah
University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84132
Contact: Bryce Moulton    801-587-3831    bryce.moulton@hsc.utah.edu   
Contact: Michelle Vowles    801-587-3831    m.l.vowles@utah.edu   
Principal Investigator: John Kriesel         
United States, Washington
UW Virology Research Clinic Recruiting
Seattle, Washington, United States, 98104
Contact: Mark Drummond    206-520-4340    mjd520@u.washington.edu   
Principal Investigator: Anna Wald, MD, MPH         
Sponsors and Collaborators
Genocea Biosciences, Inc.
  More Information

No publications provided

Responsible Party: Genocea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT02114060     History of Changes
Other Study ID Numbers: GEN-003-002
Study First Received: April 11, 2014
Last Updated: October 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Genocea Biosciences, Inc.:
HSV
Herpes
genital infection
vaccine

Additional relevant MeSH terms:
Herpes Genitalis
Herpes Simplex
DNA Virus Infections
Genital Diseases, Female
Genital Diseases, Male
Herpesviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Skin Diseases
Skin Diseases, Infectious
Skin Diseases, Viral
Virus Diseases

ClinicalTrials.gov processed this record on October 23, 2014