Dose Ranging Safety and Efficacy of Therapeutic HSV-2 Vaccine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genocea Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT02114060
First received: April 11, 2014
Last updated: March 7, 2016
Last verified: March 2016
  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 ]

Enrollment: 310
Study Start Date: July 2014
Study Completion Date: February 2016
Primary Completion Date: February 2016 (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
  • 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 Name: 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
  • 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 Name: 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
  • 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 Name: 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
  • 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 Name: 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
  • 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 Name: 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
  • 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 Name: 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   (Adult)
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
Birmingham, Alabama, United States, 35294-0006
United States, California
Medical Center for Clinical Research
San Diego, California, United States, 92108
Quest Clinical Research
San Francisco, California, United States, 94115
United States, Illinois
University of Illinois Department of Medicine
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana University Infectious Disease Research
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
The Fenway Institute
Boston, Massachusetts, United States, 02215
United States, North Carolina
UNC Global HIV Prevention and Treatment Clinical Trials Unit
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Oregon
Westover Heights Clinic
Portland, Oregon, United States, 97210
United States, Pennsylvania
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Tekton Research
Austin, Texas, United States, 98745
Center for Clinical Studies - Houston
Houston, Texas, United States, 77030
Center for Clinical Studies
Houston, Texas, United States, 77065
Center for Clinical Studies - Clear Lake/Webster
Webster, Texas, United States, 77598
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
UW Virology Research Clinic
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Genocea Biosciences, Inc.
  More Information

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: March 7, 2016
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Herpes Simplex
Herpes Genitalis
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Genital Diseases, Male
Genital Diseases, Female
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 27, 2016