Evaluating New Formulation of Therapeutic HSV-2 Vaccine

Study Overview
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Brief Summary
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This study evaluates the reduction in viral shedding after vaccination with a new formulation of GEN-003 in subjects with genital HSV-2 infection. Two-thirds of the participants will receive GEN-003, one-third will receive placebo.

Detailed Description
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This study is a randomized, double-blind, placebo-controlled clinical trial of a new formulation of GEN-003 for treatment of HSV-2 genital infection. 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 then complete a second set of anogenital swabs for 28 consecutive days after the third dose. Each subject will be followed for one year after the third dose.

Official Title
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A Randomized, Double-Blind Study to Evaluate a New Formulation of GEN-003 in Subjects With Genital HSV-2 Infection

Conditions
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Genital Herpes Simplex Type 2

Intervention / Treatment
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* Biological: Matrix-M2
* Biological: GEN-003
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria A history of at least 3 and no more than 9 reported clinical occurrences in the prior 12 months, or, if currently on suppressive antiviral therapy, a history of at least 3 and no more than 9 reported clinical occurrences in the 12 months prior to initiation of antiviral suppressive therapy Diagnosis of genital HSV-2 infection for > 1 year Willing and able to provide written informed consent Willing to perform and comply with all study procedures including attending clinic visits as scheduled and completion of an electronic lesion report form Willing to not use suppressive antiviral therapy from 14 days prior to starting the study and for the duration of the study Men and women must be willing to practice a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with vasectomized partner, vasectomy, tubal ligation, hysterectomy, licensed hormonal methods, intrauterine device, or barrier method (e.g., condom, diaphragm) with spermicide for 28 days before and 90 days after receiving the Study Drug Exclusion Criteria On suppressive antiviral therapy within 14 days of starting the study Use of topical steroids or antiviral medication in the anogenital region within 14 days of starting the study and during study Use of tenofovir, lysine, or other medication or supplement known or purported to affect HSV outbreak frequency or intensity within 14 days of starting the study History of any form of ocular HSV infection, HSV-related erythema multiforme, or herpes meningitis or encephalitis Immunocompromised individuals Use of corticosteroids within 30 days of starting the study and during the study or other immunosuppressive agents Presence or history of autoimmune disease regardless of current treatment Current infection with HIV or hepatitis B or C virus History of hypersensitivity to any component of the vaccine Prior receipt of GEN-003 or another vaccine containing HSV-2 antigens Receipt of any investigational product within 30 days prior to Dose 1 Receipt of blood products within 90 days prior to Dose 1 Planned use of any vaccine over the course of the study Pregnant or nursing women History of drug or alcohol abuse Other active, uncontrolled comorbidities

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GEN-003 60ug / Matrix-M2 50ug<br>GEN-003/M2 (60 ug of each antigen) with Matrix-M2 adjuvant (50ug), administered as a 0.5mL intramuscular (IM) injection | Biological: Matrix-M2<br>* Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.<br>* Other names: Adjuvant;Biological: GEN-003<br>* HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D<br>* Other names: HSV Therapeutic Vaccine;|
| Experimental: GEN-003 60ug / Matrix-M2 75ug<br>GEN-003/M2 (60 ug of each antigen) with Matrix-M2 adjuvant (75ug), administered as a 0.5mL intramuscular (IM) injection | Biological: Matrix-M2<br>* Matrix-M2 is derived from fractionated Quillaja saponins, phosphatidylcholine, and cholesterol.<br>* Other names: Adjuvant;Biological: GEN-003<br>* HSV-2 protein subunit vaccine consisting of 2 recombinant T cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D<br>* Other names: HSV Therapeutic Vaccine;|
| Placebo Comparator: Placebo<br>0.9% Normal Saline administered as a 0.5 mL intramuscular (IM) injection | Drug: Placebo<br>* 0.9% Normal Saline<br>* Other names: 0.9% Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HSV-2 viral shedding rate |  | baseline (Days -28 to Day 1) and after vaccination (Days 43 to 71) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity measured by humoral (antibody) responses to vaccine antigens |  | 13 weeks | 
| Impact on clinical HSV-2 disease based on time to first recurrence |  | 64 weeks | 
| Number of patients with adverse events as a measure of safety and tolerability |  | 64 weeks | 
| Reduction in HSV-2 viral shedding rate |  | After vaccination (6 Months and 12 Months) | 
| Impact on clinical HSV-2 disease based on lesion rate |  | 64 weeks | 
| Impact on clinical HSV-2 disease based on percent recurrence-free |  | 64 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSV, Herpes, Genital Herpes, Vaccine