Dose Ranging Safety and Efficacy of Therapeutic HSV-2 Vaccine
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
1 other identifier
interventional
310
1 country
16
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2014
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 11, 2014
CompletedFirst Posted
Study publicly available on registry
April 15, 2014
CompletedStudy Start
First participant enrolled
July 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2016
CompletedOctober 16, 2017
October 1, 2017
1.6 years
April 11, 2014
October 6, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in proportion of days with detectable viral shedding
6 weeks
Secondary Outcomes (3)
Immunogenicity measured by humoral (antibody) and T-cell responses to vaccine antigens
33 weeks
Impact on clinical HSV-2 disease based on time to recurrence and lesion rate
53 weeks
Number of patients with adverse events as a measure of safety and tolerability
57 weeks
Study Arms (7)
GEN-003 Vaccine 30μg / Matrix-M 25μg
EXPERIMENTALGEN-003 Vaccine (30 μg of each antigen) with Matrix-M2 adjuvant (25 μg), administered as a 0.5 mL intramuscular (IM) injection.
GEN-003 Vaccine 30μg / Matrix-M2 50μg
EXPERIMENTALGEN-003 Vaccine (30 μg of each antigen) with Matrix-M2 adjuvant (50 μg), administered as a 0.5 mL intramuscular (IM) injection.
GEN-003 Vaccine 30μg / Matrix-M2 75μg
EXPERIMENTALGEN-003 Vaccine (30 μg of each antigen) with Matrix-M2 adjuvant (75 μg), administered as a 0.5 mL intramuscular (IM) injection.
GEN-003 Vaccine 60μg / Matrix-M2 25μg
EXPERIMENTALGEN-003 Vaccine (60 μg of each antigen) with Matrix-M2 adjuvant (25 μg), administered as a 0.5 mL intramuscular (IM) injection.
GEN-003 Vaccine 60μg / Matrix-M2 50μg
EXPERIMENTALGEN-003 Vaccine (60 μg of each antigen) with Matrix-M2 adjuvant (50 μg), administered as a 0.5 mL intramuscular (IM) injection.
GEN-003 Vaccine 60μg / Matrix-M2 75μg
EXPERIMENTALGEN-003 Vaccine (60 μg of each antigen) with Matrix-M2 adjuvant (75 μg), administered as a 0.5 mL intramuscular (IM) injection.
Placebo
PLACEBO COMPARATOR0.9% Normal Saline administered as a 0.5 mL intramuscular (IM) injection.
Interventions
HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D
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 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.
Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.
Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
University of Alabama Vaccine Research Unit
Birmingham, Alabama, 35294-0006, United States
Medical Center for Clinical Research
San Diego, California, 92108, United States
Quest Clinical Research
San Francisco, California, 94115, United States
University of Illinois Department of Medicine
Chicago, Illinois, 60612, United States
Indiana University Infectious Disease Research
Indianapolis, Indiana, 46202, United States
The Fenway Institute
Boston, Massachusetts, 02215, United States
UNC Global HIV Prevention and Treatment Clinical Trials Unit
Chapel Hill, North Carolina, 27599, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039, United States
Westover Heights Clinic
Portland, Oregon, 97210, United States
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213, United States
Tekton Research
Austin, Texas, 98745, United States
Center for Clinical Studies - Houston
Houston, Texas, 77030, United States
Center for Clinical Studies
Houston, Texas, 77065, United States
Center for Clinical Studies - Clear Lake/Webster
Webster, Texas, 77598, United States
University of Utah
Salt Lake City, Utah, 84132, United States
UW Virology Research Clinic
Seattle, Washington, 98104, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 11, 2014
First Posted
April 15, 2014
Study Start
July 1, 2014
Primary Completion
February 1, 2016
Study Completion
February 1, 2016
Last Updated
October 16, 2017
Record last verified: 2017-10