Dose Ranging Safety and Efficacy of Therapeutic HSV-2 Vaccine

NCT ID: NCT02114060

Last Updated: 2017-10-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

310 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-31

Study Completion Date

2016-02-29

Brief Summary

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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.

Detailed Description

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Conditions

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Genital Herpes Simplex Type 2

Keywords

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HSV Herpes genital infection vaccine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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GEN-003 Vaccine 30μg / Matrix-M 25μg

GEN-003 Vaccine (30 μg of each antigen) with Matrix-M2 adjuvant (25 μg), administered as a 0.5 mL intramuscular (IM) injection.

Group Type EXPERIMENTAL

GEN-003 Vaccine (30μg of each antigen)

Intervention Type BIOLOGICAL

HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D

Matrix-M2 Adjuvant (25μg)

Intervention Type BIOLOGICAL

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

GEN-003 Vaccine 30μg / Matrix-M2 50μg

GEN-003 Vaccine (30 μg of each antigen) with Matrix-M2 adjuvant (50 μg), administered as a 0.5 mL intramuscular (IM) injection.

Group Type EXPERIMENTAL

GEN-003 Vaccine (30μg of each antigen)

Intervention Type BIOLOGICAL

HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D

Matrix-M2 Adjuvant (50μg)

Intervention Type BIOLOGICAL

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

GEN-003 Vaccine 30μg / Matrix-M2 75μg

GEN-003 Vaccine (30 μg of each antigen) with Matrix-M2 adjuvant (75 μg), administered as a 0.5 mL intramuscular (IM) injection.

Group Type EXPERIMENTAL

GEN-003 Vaccine (30μg of each antigen)

Intervention Type BIOLOGICAL

HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D

Matrix-M2 Adjuvant (75μg)

Intervention Type BIOLOGICAL

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

GEN-003 Vaccine 60μg / Matrix-M2 25μg

GEN-003 Vaccine (60 μg of each antigen) with Matrix-M2 adjuvant (25 μg), administered as a 0.5 mL intramuscular (IM) injection.

Group Type EXPERIMENTAL

GEN-003 Vaccine (60μg of each antigen)

Intervention Type BIOLOGICAL

HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D

Matrix-M2 Adjuvant (25μg)

Intervention Type BIOLOGICAL

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

GEN-003 Vaccine 60μg / Matrix-M2 50μg

GEN-003 Vaccine (60 μg of each antigen) with Matrix-M2 adjuvant (50 μg), administered as a 0.5 mL intramuscular (IM) injection.

Group Type EXPERIMENTAL

GEN-003 Vaccine (60μg of each antigen)

Intervention Type BIOLOGICAL

HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D

Matrix-M2 Adjuvant (50μg)

Intervention Type BIOLOGICAL

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

GEN-003 Vaccine 60μg / Matrix-M2 75μg

GEN-003 Vaccine (60 μg of each antigen) with Matrix-M2 adjuvant (75 μg), administered as a 0.5 mL intramuscular (IM) injection.

Group Type EXPERIMENTAL

GEN-003 Vaccine (60μg of each antigen)

Intervention Type BIOLOGICAL

HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D

Matrix-M2 Adjuvant (75μg)

Intervention Type BIOLOGICAL

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

Placebo

0.9% Normal Saline administered as a 0.5 mL intramuscular (IM) injection.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

0.9% Normal Saline (NaCl)

Interventions

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GEN-003 Vaccine (30μg of each antigen)

HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D

Intervention Type BIOLOGICAL

GEN-003 Vaccine (60μg of each antigen)

HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D

Intervention Type BIOLOGICAL

Matrix-M2 Adjuvant (25μg)

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

Intervention Type BIOLOGICAL

Matrix-M2 Adjuvant (50μg)

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

Intervention Type BIOLOGICAL

Matrix-M2 Adjuvant (75μg)

Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.

Intervention Type BIOLOGICAL

Placebo

0.9% Normal Saline (NaCl)

Intervention Type BIOLOGICAL

Other Intervention Names

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HSV Vaccine HSV Vaccine MM2 Adjuvant MM2 Adjuvant MM2 Adjuvant 0.9% Normal Saline (NaCl)

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genocea Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama Vaccine Research Unit

Birmingham, Alabama, United States

Site Status

Medical Center for Clinical Research

San Diego, California, United States

Site Status

Quest Clinical Research

San Francisco, California, United States

Site Status

University of Illinois Department of Medicine

Chicago, Illinois, United States

Site Status

Indiana University Infectious Disease Research

Indianapolis, Indiana, United States

Site Status

The Fenway Institute

Boston, Massachusetts, United States

Site Status

UNC Global HIV Prevention and Treatment Clinical Trials Unit

Chapel Hill, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Westover Heights Clinic

Portland, Oregon, United States

Site Status

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Tekton Research

Austin, Texas, United States

Site Status

Center for Clinical Studies - Houston

Houston, Texas, United States

Site Status

Center for Clinical Studies

Houston, Texas, United States

Site Status

Center for Clinical Studies - Clear Lake/Webster

Webster, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

UW Virology Research Clinic

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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GEN-003-002

Identifier Type: -

Identifier Source: org_study_id