Herpes Simplex Type 2
Conditions
Keywords
herpes simplex virus type 2,, genital herpes
Brief summary
The purpose of this study is to evaluate the effect of recombinant human heat shock protein 70-polyvalent peptide complex (HerpV) vaccine administration on recurring episodes of genital herpes by evaluating viral shedding before and after treatment.
Detailed description
This study will evaluate the biological effectiveness and safety of the HerpV vaccine in combination with adjuvant QS-21. The Safety and tolerability of HerpV plus QS-21 will also be evaluated by collecting number and severity of adverse events throughout the study. Participants will undergo a baseline/ screening period. This is a 45 day period when the participant collects a swab of the genital area each day. In case of a recurrence, participant will be required to collect two swabs a day. If the participant collects at least 80% of the swabbing samples and meets all eligibility criteria they may enroll in the study. Study Period 1 consists of three treatments and a 45 day swabbing period after the last treatment. The participant will collect swabs of the genital region each day for 45 days. Participants who successfully complete Study Period 1 will proceed to Study Period 2. They will receive a booster injection of study drug or placebo according to their original randomization assignment. The participants will again enter a 45 day swabbing period, collecting swabs of the genital area each day for 45 days.
Interventions
DRUGHerpV and QS-21
HerpV (recombinant human heat shock protein 70 \[rh-Hsc70\] polyvalent peptide complex) in combination with adjuvant QS-21
DRUGPlacebo
phosphate buffered saline
Sponsors
Agenus Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Seropositive for herpes simplex virus type 2 (HSV-2) * Clinically active genital herpes defined as a history of 1-9 episodes per year for at least 1 year prior to screening or 1 year prior to beginning suppressive therapy. * Willing to either use an effective method of contraception or abstain from sexual intercourse throughout the 48-week study period. * If female of childbearing potential, have a negative serum pregnancy test. * Agree to not receive any other investigational drugs while enrolled in this study. * The above criteria must be met before participants are allowed to enter the 45-day swabbing period to be screen for the study. * Completion and collection of greater than or equal to 80% (36 days) of the 45-day consecutive daily genital swabs.
Exclusion criteria
* Severe active infection, compromised cardiopulmonary function, or other serious medical illness that, in the opinion of the principal investigator, would prevent study completion. * A history of herpes simplex virus (HSV) infection of the eye (herpes simplex interstitial keratitis or uveitis), or herpes-associated erythema multiforme. * A history of immune suppression or autoimmune disorder. * Continued use of suppressive anti-viral therapy for HSV-2; a 1 week washout of any anti-viral therapy (suppressive and episodic) is required prior to initiating the swabbing period. * Concomitant use of systemic corticosteroids or immune-suppressive medications. The use of nasal steroids is acceptable. * Human immunodeficiency virus (HIV) positive. * Presence of active Hepatitis B or C infection. * Known hypersensitivity or allergies to acyclovir or valacyclovir. * Pregnant or breast-feeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Overall Viral Shedding Rate From Baseline (Week -7 to 0) to Post-treatment Period (Weeks 6 to 13) | Baseline, Weeks 6-13 | The viral shedding rate was defined as the number of days with genital swab positive for herpes simplex virus (HSV) deoxyribonucleic acid (DNA), as measured by quantitative real-time polymerase chain reaction (PCR), relative to the total number of days with available swabs. The viral shedding rate was defined as the number of days with genital swab positive for herpes simplex virus (HSV) deoxyribonucleic acid (DNA), as measured by quantitative real-time polymerase chain reaction (PCR), relative to the total number of days with available swabs. Overall viral shedding rate = number of days with positive PCR/total number of days PCR results collected. Change in overall viral shedding rate was calculated within participants comparing baseline with post-treatment, and summarized across all participants. Percent change in viral shedding rate and 95% CI are reported. |
| Percent Change in Overall Viral Shedding Rate From Baseline (Week -7 to 0) to Post-treatment Period (Weeks 26 to 33) | Baseline, Weeks 26-33 | The viral shedding rate was defined as the number of days with genital swab positive for HSV DNA, as measured by quantitative real-time PCR, relative to the total number of days with available swabs. The viral shedding rate was defined as the number of days with genital swab positive for herpes simplex virus (HSV) deoxyribonucleic acid (DNA), as measured by quantitative real-time polymerase chain reaction (PCR), relative to the total number of days with available swabs. Overall viral shedding rate = number of days with positive PCR/total number of days PCR results collected. Change in overall viral shedding rate was calculated within participants comparing baseline with post-treatment, and summarized across all participants. Percent change in viral shedding rate and 95% CI are reported. |
Other
| Measure | Time frame |
|---|---|
| Number of Participants With Peripheral Blood Mononuclear Cell Immune Response at Any Time | Baseline through Week 26 |
| Number of Participants With CD8+ Immune Response at Any Time | Baseline through Week 26 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HerpV + QS-21 Participants received a combination of HerpV 240 μg and QS-21 50 μg injection subcutaneously at Weeks 0, 2 and 4 in treatment period 1. At Week 24, participants who completed treatment period 1 received a booster dose of combination of HerpV 240 μg and QS-21 50 μg in treatment period 2. Each treatment period was followed by a washout period of 1 week. | 70 |
| Placebo Participants received placebo (PBS) injection subcutaneously at Weeks 0, 2 and 4 in treatment period 1 and at Week 24 in treatment period 2. Each treatment period was followed by a washout period of 1 week. | 10 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator's decision | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Noncompliance | 1 | 2 |
| Overall Study | Other than specified | 56 | 7 |
| Overall Study | Sponsor's decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 0 |
Baseline characteristics
| Characteristic | HerpV + QS-21 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 35.9 years STANDARD_DEVIATION 8 | 33.7 years STANDARD_DEVIATION 6.22 | 35.6 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 42 Participants | 6 Participants | 48 Participants |
| Sex: Female, Male Male | 28 Participants | 4 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 70 | 10 / 10 |
| serious Total, serious adverse events | 3 / 70 | 0 / 10 |
Outcome results
Primary
Percent Change in Overall Viral Shedding Rate From Baseline (Week -7 to 0) to Post-treatment Period (Weeks 26 to 33)
The viral shedding rate was defined as the number of days with genital swab positive for HSV DNA, as measured by quantitative real-time PCR, relative to the total number of days with available swabs. The viral shedding rate was defined as the number of days with genital swab positive for herpes simplex virus (HSV) deoxyribonucleic acid (DNA), as measured by quantitative real-time polymerase chain reaction (PCR), relative to the total number of days with available swabs. Overall viral shedding rate = number of days with positive PCR/total number of days PCR results collected. Change in overall viral shedding rate was calculated within participants comparing baseline with post-treatment, and summarized across all participants. Percent change in viral shedding rate and 95% CI are reported.
Time frame: Baseline, Weeks 26-33
Population: Efficacy population included all randomized participants who received all 3 vaccinations of Herp-V vaccine and were compliant with the study procedures. This outcome measure was planned to be analyzed for HerpV + QS-21 arm only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HerpV + QS-21 | Percent Change in Overall Viral Shedding Rate From Baseline (Week -7 to 0) to Post-treatment Period (Weeks 26 to 33) | 12.78 percentage change |
Primary
Percent Change in Overall Viral Shedding Rate From Baseline (Week -7 to 0) to Post-treatment Period (Weeks 6 to 13)
The viral shedding rate was defined as the number of days with genital swab positive for herpes simplex virus (HSV) deoxyribonucleic acid (DNA), as measured by quantitative real-time polymerase chain reaction (PCR), relative to the total number of days with available swabs. The viral shedding rate was defined as the number of days with genital swab positive for herpes simplex virus (HSV) deoxyribonucleic acid (DNA), as measured by quantitative real-time polymerase chain reaction (PCR), relative to the total number of days with available swabs. Overall viral shedding rate = number of days with positive PCR/total number of days PCR results collected. Change in overall viral shedding rate was calculated within participants comparing baseline with post-treatment, and summarized across all participants. Percent change in viral shedding rate and 95% CI are reported.
Time frame: Baseline, Weeks 6-13
Population: Efficacy population included all randomized participants who received all 3 vaccinations of Herp-V vaccine and were compliant with the study procedures. This outcome measure was planned to be analyzed for HerpV + QS-21 arm only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HerpV + QS-21 | Percent Change in Overall Viral Shedding Rate From Baseline (Week -7 to 0) to Post-treatment Period (Weeks 6 to 13) | 13.53 percentage change |
Other Pre-specified
Number of Participants With CD8+ Immune Response at Any Time
Time frame: Baseline through Week 26
Population: Efficacy population included all randomized participants who received all 3 vaccinations of Herp-V vaccine and were compliant with the study procedures. Here, Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HerpV + QS-21 | Number of Participants With CD8+ Immune Response at Any Time | 32 Participants |
| Placebo | Number of Participants With CD8+ Immune Response at Any Time | 2 Participants |
Other Pre-specified
Number of Participants With Peripheral Blood Mononuclear Cell Immune Response at Any Time
Time frame: Baseline through Week 26
Population: Efficacy population included all randomized participants who received all 3 vaccinations of Herp-V vaccine and were compliant with the study procedures. Here, Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HerpV + QS-21 | Number of Participants With Peripheral Blood Mononuclear Cell Immune Response at Any Time | 46 Participants |
| Placebo | Number of Participants With Peripheral Blood Mononuclear Cell Immune Response at Any Time | 1 Participants |