Clinical trial NCT02114060: Dose Ranging Safety and Efficacy of Therapeutic HSV-2 Vaccine
Official title: A Randomized, Double-Blind, Factorial Study to Compare the Safety and Efficacy of Varying Combinations of GEN-003 and Matrix-M2 in Subjects With Genital HSV-2 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Genital Herpes Simplex Type 2
Keywords: HSV
Herpes
genital infection
vaccine
Lead sponsor: Genocea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2014-04-15
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, factorial study to compare the reduction in viral shedding among 6 different combinations of GEN-003, a therapeutic HSV-2 vaccine and Matrix-M2 adjuvant.

Secondary objectives of the study include:

* Evaluation of the safety and tolerability of GEN-003 in combination with Matrix-M2 compared to placebo.
* Comparison of the impact on clinical Herpes Simplex Virus type-2 (HSV-2) disease among the 6 different combinations of GEN-003 antigens and Matrix-M2 adjuvant measured by:

  * Time to first clinical and/or virologic recurrence,
  * Proportion of subjects who are recurrence free at 6 and 12 months after the last dose of vaccine,
  * Lesion rate (percent of days with genital lesions present) during the post-vaccination swabbing periods.
* Evaluation of cellular and humoral responses to GEN-003 antigens.

Additional objectives include:

* Assessment of the correlation between immune responses and change in viral shedding or impact on clinical disease as defined above.
* Determination of the recurrence rate in a subset of subjects not receiving suppressive antivirals throughout the study.

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. Subjects will be followed for safety and immunologic response for 12 months following their last dose.


Eligibility criteria: Inclusion Criteria:

* Males and non-pregnant females, ages 18 to 50 years inclusive.
* 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
* Positive HerpeSelect® 2 Enzyme-linked Immunosorbent Assay (ELISA) Immunoglobulin G (IgG) with an index value \>3.5, or
* Positive LIAISON® HSV-2 Type-Specific IgG
* 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 of suppressive therapy.
* Collection of at least 45 of 56 anogenital swabs during the baseline period.
* Willing and able to provide written informed consent.
* Willing to perform and comply with all study procedures including attending clinic visits as scheduled.
* Men and women of childbearing potential, must be willing to practice a highly effective method of contraception that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, vasectomy, licensed hormonal methods, intrauterine device (IUD), or barrier method (e.g., condom, diaphragm) for 28 days before and 90 days after receiving Study Drug.

Exclusion Criteria:

* On suppressive antiviral medication within 7 days of beginning baseline anogenital swab collection period.
* History of genital Herpes Simplex Virus type-1 (HSV-1) infection.
* History of any form of ocular Herpes Simplex Virus (HSV) infection, HSV-related erythema multiforme, or herpes meningitis or encephalitis.
* Immunocompromised individuals, including those receiving immunosuppressive doses of corticosteroids (more than 20 mg of prednisone given daily or on alternative days for 2 weeks or more within 6 months prior to the first dose of Study Drug, any dose of corticosteroids within 30 days of the first dose of Study Drug, or high dose inhaled corticosteroids \[\> 960 μg/day of beclomethasone dipropionate or equivalent\]) or other immunosuppressive agents.
* Presence or history of autoimmune disease, regardless of current treatment.
* Positive serologic test for Human Immunodeficiency Virus (HIV-1) or hepatitis C infection; positive hepatitis B surface antigen (HBsAg).
* Clinically significant laboratory abnormality or a value ≥ Grade 2.
* Prior immunization with a vaccine containing HSV-2 antigens.
* History of hypersensitivity to any component of the vaccine.
* Receipt of any investigational drug within 30 days prior to the first dose of Study Drug.
* Receipt of blood products within 90 days prior to the first dose of Study Drug.
* Receipt of a live vaccine within 28 days prior to or a subunit vaccine within 14 days prior to the first dose of Study Drug or planned vaccination within 30 days following the last dose of Study Drug.
* Pregnant or nursing women.
* 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.
* Other active, uncontrolled co-morbidities that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the study requirements.

NOTE: Subjects who are taking a medication to control an underlying co-morbidity may be enrolled if there have been no changes to their medication within 60 days prior to the first dose of Study Drug.

Primary outcomes:
measure: Change in proportion of days with detectable viral shedding
timeFrame: 6 weeks
Secondary outcomes:
measure: Immunogenicity measured by humoral (antibody) and T-cell responses to vaccine antigens
timeFrame: 33 weeks
measure: Impact on clinical HSV-2 disease based on time to recurrence and lesion rate
timeFrame: 53 weeks
measure: Number of patients with adverse events as a measure of safety and tolerability
timeFrame: 57 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Vaccine Research Unit
state: Alabama
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Chicago
country: United States
facility: University of Illinois Department of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Infectious Disease Research
state: Indiana
city: Boston
country: United States
facility: The Fenway Institute
state: Massachusetts
city: Chapel Hill
country: United States
facility: UNC Global HIV Prevention and Treatment Clinical Trials Unit
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Westover Heights Clinic
state: Oregon
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies - Houston
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies
state: Texas
city: Webster
country: United States
facility: Center for Clinical Studies - Clear Lake/Webster
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: UW Virology Research Clinic
state: Washington
Study officials:
References: