Safety and Immunogenicity Study of Therapeutic HSV-2 Vaccine

Study Overview
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Brief Summary
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Randomized, double-blind, placebo-controlled, dose escalation study. There will be 3 cohorts of patients defined by the antigen dose (10, 30 or 100 µg of each antigen), and within each cohort, patients will be randomized at a ratio of 3:1:1 to one of the following: GEN-003/M2: GEN-003 plus Matrix M-2 adjuvant (50 µg per dose) GEN-003: Antigens alone Placebo (DPBS diluent) Each Cohort is divided into 2 Groups. For each dose cohort, immunizations begin with a Pilot Group. Immunization of the remainder of the Group Continuation Group) is contingent upon successful review of data from the Pilot Group through Day 7 after immunization. Dose escalation to the next dose level Cohort proceeds after evaluation of safety data from all patients in the prior Cohort and only after all specified safety criteria are met. The total numbers of patients in each Group and Cohort are as follows: 10 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total) 30 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total) 100 µg Cohort: 10 Pilot Group, 40 Continuation Group (50 Total) Totals per group: 30 Pilot Group, 120 Continuation Group (150 Total Patients) Subjects will receive 3 doses of the assigned treatment (GEN-003/M-2, GEN-003, or placebo) at 3 week intervals. Sampling from mucocutaneous genital sites for viral shedding will be done twice daily for 28 days prior to the first immunization (baseline shedding), and again following the last immunization. Follow-up for safety monitoring will be conducted for 12 months after the last immunization.

Official Title
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A Phase I/IIa, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study of the Safety and Immunogenicity of a HSV-2 Vaccine Containing Matrix M-2 Adjuvant in Individuals With Documented Genital HSV-2 Genital Infection

Conditions
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Genital Herpes Simplex Type 2

Intervention / Treatment
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* Biological: GEN-003 with Matrix M-2
* Biological: GEN-003
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ages 18 to 50 years, inclusive. Willing to practice a highly effective method of contraception that includes the use of a barrier method such as a condom. 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 HSV-2 ELISA (HerpSelect) index value >3.5 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 suppressive therapy. Good general health status as determined by screening evaluation completed within 90 days prior to immunization. Any out of range screening clinical laboratory values should be considered not clinically significant by the Investigator. Patient has provided written informed consent. Ability and willingness to perform and comply with all study procedures including attending clinic visits as scheduled. Note: patients must provide, by the day of randomization, a minimum of 28 (equivalent of 14 days) baseline viral swab samples to continue to be eligible and be randomized). Exclusion Criteria: On suppressive antiviral medication within 7 days of baseline viral shedding evaluation. Immunocompromised individuals, including those receiving systemic corticosteroids or other immunosuppressive agents. Positive serologic test for HIV-1 infection; positive hepatitis B surface antigen (HBsAg) or antibody for hepatitis C (anti-HCV). Active lesions consistent with herpetic disease at the time of scheduled immunization. Pregnant or nursing women. Receipt of any investigational drug within 30 days of the first scheduled day of immunization. History of hypersensitivity to any component of the vaccine. History of genital HSV-1 infection. History of: (1) any form of ocular HSV infection, (2) HSV-related erythema multiforme, or (3) herpes meningitis or encephalitis. Any other condition which in the opinion of the Investigator would interfere with the successful completion of the study protocol. 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. Prior immunization with a vaccine containing HSV-2 antigens. Receipt of blood products within 90 days of the first immunization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose GEN-003 with Matrix M-2<br>10µg GEN-003, 50µg Matrix M-2 Adjuvant | Biological: GEN-003 with Matrix M-2<br>* IM administration of GEN-003 Vaccine with 50ug Matrix M-2 Adjuvant.<br>|
| Experimental: Mid Dose GEN-003 with Matrix M-2<br>30µg GEN-003, 50µg Matrix M-2 Adjuvant | Biological: GEN-003 with Matrix M-2<br>* IM administration of GEN-003 Vaccine with 50ug Matrix M-2 Adjuvant.<br>|
| Experimental: High Dose GEN-003 with Matrix M-2<br>100µg GEN-003, 50µg Matrix M-2 Adjuvant | Biological: GEN-003 with Matrix M-2<br>* IM administration of GEN-003 Vaccine with 50ug Matrix M-2 Adjuvant.<br>|
| Experimental: Low Dose GEN-003 Only<br>10µg GEN-003 | Biological: GEN-003<br>* IM administration of GEN-003 Vaccine, antigens alone (without adjuvant).<br>|
| Experimental: Mid Dose GEN-003 Only<br>30µg GEN-003 | Biological: GEN-003<br>* IM administration of GEN-003 Vaccine, antigens alone (without adjuvant).<br>|
| Experimental: High Dose GEN-003 Only<br>100µg GEN-003 | Biological: GEN-003<br>* IM administration of GEN-003 Vaccine, antigens alone (without adjuvant).<br>|
| Placebo Comparator: Placebo<br>0.5 mL phosphate buffered saline | Biological: Placebo<br>* IM administration of 0.5 mL dose of Dulbecco's phosphate buffered saline.<br>* Other names: DPBS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events as a measure of safety and tolerability |  | 57 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity measured by humoral (antibody) and T-cell responses to vaccine antigens |  | 33 weeks | 
| Change in proportion of days with detectable viral shedding |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSV, Herpes, genital infection, vaccine