Genital Herpes, HSV-2 Infection
Conditions
Keywords
HSV, Herpes, Genital Herpes, Vaccine
Brief summary
The main purpose of this clinical study is to see if a maintenance dose of GEN-003 reduces the number of days that subjects have a genital herpes recurrence. The second purpose of the study is to evaluate the safety and tolerability of a maintenance dose of GEN-003.
Detailed description
This study is a randomized, double-blind, placebo-controlled clinical trial of GEN-003 in subjects who have received previous doses of GEN-003 in the GEN-003-003 clinical trial. Eligible subjects will be randomized in a 1:1 ratio to receive 1 intramuscular (IM) dose (the maintenance dose) of GEN-003 or placebo. Subjects will use a daily electronic reporting tool for reporting the presence or absence of genital herpes lesions, and severity of genital herpes symptoms. GEN-003-005 was originally designed to follow subjects for 12 months after the maintenance dose but a business decision, unrelated to product safety, was made by Genocea Biosciences in 3Q2017 to cease GEN-003 spending and activities.
Interventions
BIOLOGICALGEN-003
HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP4 and glycoprotein D
BIOLOGICALMatrix-M2
Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.
OTHER0.9% normal saline
Placebo
Sponsors
Genocea Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Completed Study GEN-003-003 * Received all 3 GEN-003 doses (any dose combination) in Study GEN-003-003 * Received last dose of GEN-003 within 11 to 18 months prior * Reported data in the daily electronic reporting period on at least 80% of days in Study GEN-003-003 * Collected at least 45 swabs (of 56 total expected swabs) during the Month 11 to 12 swab collection period in Study GEN-003-003 * Willing and able to provide written informed consent * Willing to perform and comply with all study procedures * Postmenopausal or willing to practice a highly effective method of contraception for 28 days before and 90 days after enrollment
Exclusion criteria
* Did not meet all eligibility criteria in Study GEN-003-003, or received incorrect treatment in Study GEN-003-003 * Use of suppressive antiviral medication within 14 days prior * Use of topical steroids or antiviral medication in the anogenital region within 14 days prior * Use of tenofovir, lysine, or other medication or supplement known or purported to affect HSV recurrence frequency or intensity within 14 days prior * History of any form of ocular HSV infection, HSV-related erythema multiforme, or herpes meningitis or encephalitis * Immunocompromised individuals * Diagnosis or suspicion of an AESI * Diagnosis or suspicion of any other autoimmune disease not listed in Appendix 4 of the protocol * Vaccine-related SAE in GEN-003-003 * Known current infection with HIV or hepatitis B or C virus * History of hypersensitivity to any component of the vaccine * Prior receipt of another vaccine containing HSV-2 antigens other than GEN-003 * Receipt of any IP within 30 days prior to the maintenance dose of GEN-003/placebo * Receipt of any blood product within 90 days prior to the maintenance dose * Receipt of a live vaccine within 28 days prior to or any other vaccine within 14 days prior to maintenance dose * Planned use of any vaccine from the maintenance dose to 28 days after the maintenance dose * Pregnant or nursing women * History of drug or alcohol abuse * Other active, uncontrolled comorbidities * Changes to medication used to manage an underlying comorbidity within 60 days prior
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days With Genital Herpes Lesions | The 6-month period after vaccination | Subject-reported via electronic diary |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Genital Herpes Recurrences | The 6-month period after vaccination | Subject-reported via electronic diary |
| Number of Subjects Without Genital Herpes Recurrence | 6 months after vaccination | Subject-reported via electronic diary |
| Days Until First Genital Herpes Recurrence | The 6-month period after vaccination | Subject-reported via electronic diary |
| Duration of Genital Herpes Recurrences | The 6-month period after vaccination | Time in days per genital herpes recurrence |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GEN-003 60μg of each GEN-003 antigen with 50μg Matrix-M2 adjuvant, administered as a 0.5mL intramuscular (IM) injection
GEN-003: HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP4 and glycoprotein D
Matrix-M2: Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol. | 16 |
| Placebo 0.9% normal saline administered as a 0.5mL intramuscular (IM) injection
0.9% normal saline: Placebo | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | GEN-003 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 39.9 years | 40.1 years | 40.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 30 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 19 Participants | 8 Participants |
| Region of Enrollment United States | 16 participants | 33 participants | 17 participants |
| Sex: Female, Male Female | 11 Participants | 23 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 5 Participants |
| Weight | 82.34 kilograms | 80.72 kilograms | 79.20 kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 16 / 16 | 10 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Percentage of Days With Genital Herpes Lesions
Subject-reported via electronic diary
Time frame: The 6-month period after vaccination
Population: Results for the placebo group are based on 16 subjects, after excluding one subject who reported no electronic diary lesion data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GEN-003 | Percentage of Days With Genital Herpes Lesions | 2.58 percentage of days |
| Placebo | Percentage of Days With Genital Herpes Lesions | 4.23 percentage of days |
p-value: 0.7474Wilcoxon (Mann-Whitney)
Secondary
Days Until First Genital Herpes Recurrence
Subject-reported via electronic diary
Time frame: The 6-month period after vaccination
Population: Results for the placebo group are based on 16 subjects, after excluding one subject who reported no electronic diary lesion data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GEN-003 | Days Until First Genital Herpes Recurrence | 25 days |
| Placebo | Days Until First Genital Herpes Recurrence | 51 days |
p-value: 0.3869Log Rank
Secondary
Duration of Genital Herpes Recurrences
Time in days per genital herpes recurrence
Time frame: The 6-month period after vaccination
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GEN-003 | Duration of Genital Herpes Recurrences | 2.83 days |
| Placebo | Duration of Genital Herpes Recurrences | 3.40 days |
p-value: 0.22Wilcoxon (Mann-Whitney)
Secondary
Number of Genital Herpes Recurrences
Subject-reported via electronic diary
Time frame: The 6-month period after vaccination
Population: Results for the placebo group are based on 16 subjects, after excluding one subject who reported no electronic diary lesion data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GEN-003 | Number of Genital Herpes Recurrences | 1.50 recurrences |
| Placebo | Number of Genital Herpes Recurrences | 1.50 recurrences |
p-value: 0.645Wilcoxon (Mann-Whitney)
Secondary
Number of Subjects Without Genital Herpes Recurrence
Subject-reported via electronic diary
Time frame: 6 months after vaccination
Population: Results for the placebo group are based on 16 subjects, after excluding one subject who reported no electronic diary lesion data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GEN-003 | Number of Subjects Without Genital Herpes Recurrence | No Recurrence | 1 Participants |
| GEN-003 | Number of Subjects Without Genital Herpes Recurrence | With Recurrence | 13 Participants |
| GEN-003 | Number of Subjects Without Genital Herpes Recurrence | Unknown | 2 Participants |
| Placebo | Number of Subjects Without Genital Herpes Recurrence | No Recurrence | 3 Participants |
| Placebo | Number of Subjects Without Genital Herpes Recurrence | With Recurrence | 12 Participants |
| Placebo | Number of Subjects Without Genital Herpes Recurrence | Unknown | 1 Participants |
p-value: 0.3157Chi-squared