Safety and Immunogenicity Study of Therapeutic HSV-2 Vaccine

Status:	Completed
Conditions:	Infectious Disease
Therapuetic Areas:	Immunology / Infectious Diseases
Healthy:	No
Age Range:	18 - 50
Updated:	6/3/2018
Start Date:	July 2012
End Date:	May 9, 2014

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

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:

1. GEN-003/M2: GEN-003 plus Matrix M-2 adjuvant (50 µg per dose)

2. GEN-003: Antigens alone

3. 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.

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.

We found this trial at

sites

Indiana University Infectious Disease Research

Indianapolis, Indiana 46202

from

Indianapolis, IN