HerpeVac Trial for Young Women

Herpes Simplex Infection Clinical Trial

Official title:

A Double-Blind, Randomized, Controlled Phase III Study to Assess the Prophylactic Efficacy and Safety of gD-Alum/MPL Vaccine in the Prevention of Genital Herpes Disease in Young Women Who Are HSV-1 and -2 Seronegative

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00057330
• Other study ID #: 208141/039
• Secondary ID: 208141/039
• Status: Completed
• Phase: Phase 3
• Start date: January 14, 2003
• Est. completion date: August 22, 2009

Study information

• Verified date: May 2013
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to see if a herpes vaccine may prevent genital herpes disease in women who are not infected. The study will enroll approximately 7550 healthy women. These women will be randomly assigned to 1 of 2 possible study groups: herpes vaccine (experimental group) or hepatitis A vaccine (control group). Participants will receive their assigned vaccine at 0, 1, and 6 months. Participants will have 9 scheduled study visits and additional unscheduled visits for an evaluation of herpes if it is suspected. Participants will be involved in study related procedures for up to 20 months.

Description:

This study is a double-blind, randomized, controlled Phase III trial to assess the prophylactic efficacy and safety of gD-Alum/MPL vaccine in the prevention of genital herpes disease in young women who are herpes simplex virus (HSV)-1 and -2 seronegative. The primary efficacy objective is to evaluate vaccine efficacy in the prevention of genital herpes disease caused by HSV-1 and/or HSV-2 between months 2 and 20 in healthy adult women who were initially HSV-1 and HSV-2 seronegative. The secondary efficacy objectives are to: evaluate vaccine efficacy in the prevention of genital herpes disease caused by HSV-1 and/or HSV-2 occurring between the months 7 and 20; evaluate vaccine efficacy in the prevention of HSV-2 infection between months 2 and 20; and to evaluate vaccine efficacy in the prevention of HSV-2 infection occurring between months 7 and 20. The study will enroll approximately 7,550 women, ages 18-30 years. Participants will be randomized to 1 of 2 possible study groups: candidate vaccine; or control vaccine (hepatitis A vaccine). The study duration for each subject will be approximately 20 months. Study procedures will include 9 scheduled study visits (including the screening visit) and additional unscheduled visits for evaluation of suspected herpes disease episodes. Three doses of vaccine or control will be administered intramuscularly in the non-dominant deltoid on a 0, 1, and 6 month schedule. Subjects will attend clinic visits at screening, months 2, 7, 12, 16, and 20. In subjects who present with suspected herpes disease between months 17 and 20, an additional visit to collect a serum sample will be scheduled 3 months after the evaluation for suspected genital herpes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8323
• Est. completion date: August 22, 2009
• Est. primary completion date: August 22, 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• A female between, and including, 18 and 30 years of age at the time of the first vaccination.

• Written informed consent obtained from the subject.

• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

• Seronegative for HSV-1 and HSV-2 by Western blot.

• Subject must be non-childbearing potential, i.e. either surgically sterilized or, if of child bearing potential, she must be using a highly effective method of birth control (e.g., intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant®; DepoProvera®; contraceptive skin patch or cervical ring) for 30 days prior to vaccination, have a negative urine pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.

• A subject for whom the investigator believes can and will comply with the requirements of the protocol (e.g. completion of the memory aid/diary cards, return for follow-up visits, accessible by phone or pager, able to self-sample and not planning on moving from study area).

Exclusion Criteria:

• Pregnant or nursing female.

• Clinical signs or symptoms of current oro-labial, genital or non-genital HSV disease, such as swelling, papules, vesicles, pustules, ulcers, crusts, fissures, erythema, discharge, pain, burning, itching, tingling or dysuria.

• Previous vaccination against herpes.

• Previous administration of monophosphoryl lipid A (MPL) adjuvant (no vaccines currently licensed in the USA contain this).

• History of any confirmed oro-labial, genital or non-genital HSV disease or infection.

• Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.

• Planned administration/ administration of a non-study vaccine within 30 days of the first dose of the study vaccine with the following exceptions: Administration of routine Meningococcal, Hepatitis B, inactivated Influenza, and Diphtheria/Tetanus vaccine up to 8 days before the first dose of study vaccine is allowed.

• History of allergic disease or reactions likely to be exacerbated by any component of the study vaccines, e.g. aluminum, MPL, alum-MPL, 2-phenoxyethanol or neomycin.

• Any confirmed or suspected immunosuppressive or immunodeficient condition including, human immunodeficiency virus (HIV) infection.

• Acute or chronic, clinically significant (unresolved, requiring on-going medical management or medication, etc.) pulmonary, cardiovascular, hepatic or renal function abnormality, as determined by medical history or physical examination.

• Acute disease at the time of enrollment (defer vaccination until subject recovers). Acute disease is defined as the presence of a moderate or severe illness with or without fever. Study vaccine can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness.

• Oral temperature greater than or equal to 99.5º F (greater than or equal to 37.5º C) / axillary temperature greater than or equal to 99.5º (greater than or equal to 37.5º C) / tympanic temperature on oral setting greater than or equal to 99.5º F (greater than or equal to 37.5º C).

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. (For corticosteroids, this will mean prednisone or, equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled or topical steroids are allowed.)

• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

• Recent history of chronic alcohol consumption (defined as more than 5 oz of ethanol [absolute alcohol] per day) and/or drug abuse.

• History of sexually transmitted infection within 30 days preceding the first dose of study vaccine.

Related Conditions & MeSH terms

• Herpes Simplex
• Herpes Simplex Infection

Intervention

Biological:
• HSV vaccine or SB208141, GSK Biologicals' glycoprotein D (gD)-Alum/3-deacylated form of Monophosphoryl Lipid A (MPL) candidate genital herpes vaccine
the vaccine was administered intramuscularly in the non-dominant deltoid
• Havrix™, GlaxoSmithKline (GSK) Biologicals' licensed Hepatitis A vaccine
the vaccine was administered intramuscularly in the non-dominant deltoid

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Beauport	Quebec
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Surrey	British Columbia
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Truro	Nova Scotia
Canada	GSK Investigational Site	Winnipeg	Manitoba
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Arkansas City	Kansas
United States	GSK Investigational Site	Athens	Georgia
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Aurora	Colorado
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Bardstown	Kentucky
United States	GSK Investigational Site	Baton Rouge	Louisiana
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Bloomington	Indiana
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Carson	California
United States	GSK Investigational Site	Chandler	Arizona
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	College Park	Maryland
United States	GSK Investigational Site	Greenville	Pennsylvania
United States	GSK Investigational Site	Grove City	Pennsylvania
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Johnstown	Pennsylvania
United States	GSK Investigational Site	Kingston	Rhode Island
United States	GSK Investigational Site	La Crosse	Wisconsin
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Monongahela	Pennsylvania
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newton	Kansas
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Satesboro	Georgia
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Stony Brook	New York
United States	GSK Investigational Site	Tempe	Arizona
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Vallejo	California
United States	GSK Investigational Site	Webster	Texas
United States	GSK Investigational Site	Wexford	Pennsylvania
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Newly Acquired Genital Herpes Disease, Caused by Either Herpes Simplex Virus (HSV)-1 or HSV-2	Genital herpes disease was defined as signs (swelling, papules, vesicles, ulcers, crusts, fissures, erythema, or vaginal discharge) and/or symptoms (pain, burning, itching, tingling, dysuria) which developed on the skin or mucosa of the anogenital region and/or buttocks and laboratory confirmation of Herpes Simplex Virus (HSV)-1 or 2 infection (either concomitant positive HSV culture or HSV seroconversion within 6 months after onset of signs and/or symptoms). Seroconversion to HSV-1 and/or HSV-2 was defined as a positive HSV-1 and/or HSV-2 Western blot in a subject with a previously negative Western blot result for the corresponding HSV type.	Between Months 2 and 20
Secondary	Number of Subjects With Newly Acquired Genital Herpes Disease, Caused by Either Herpes Simplex Virus (HSV)-1 or HSV-2	Genital herpes disease was defined as signs (swelling, papules, vesicles, ulcers, crusts, fissures, erythema, or vaginal discharge) and/or symptoms (pain, burning, itching, tingling, dysuria) which developed on the skin or mucosa of the anogenital region and/or buttocks and laboratory confirmation of Herpes Simplex Virus (HSV)-1 or 2 infection (either concomitant positive HSV culture or HSV seroconversion within 6 months after onset of signs and/or symptoms). Seroconversion to HSV-1 and/or HSV-2 was defined as a positive HSV-1 and/or HSV-2 Western blot in a subject with a previously negative Western blot result for the corresponding HSV type.	Between Months 7 and 20
Secondary	Number of Subjects With Newly Acquired Herpes Simplex Virus (HSV)-2 Infection Confirmed by Either Virus Culture or HSV-2 Seroconversion.	The number of subjects with newly acquired HSV-2 infection confirmed by either virus culture or HSV-2 seroconversion was tabulated. Seroconversion to HSV-1 and/or HSV-2 was defined as a positive HSV-1 and/or HSV-2 Western blot in a subject with a previously negative Western blot result for the corresponding HSV type.	Between Months 2 and 20
Secondary	Number of Subjects With Newly Acquired Herpes Simplex Virus (HSV)-2 Infection Confirmed by Either Virus Culture or HSV-2 Seroconversion	The number of subjects with newly acquired HSV-2 infection confirmed by either virus culture or HSV-2 seroconversion was tabulated. Seroconversion to HSV-1 and/or HSV-2 was defined as a positive HSV-1 and/or HSV-2 Western blot in a subject with a previously negative Western blot result for the corresponding HSV type.	Between Months 7 and 20
Secondary	Concentrations for Anti-glycoprotein D (Anti-gD) Antibodies.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per milliliter (EU/mL). The seroprotection cut-off of the assay was 40 EU/mL	At Months 0, 2, 6, 7, 12, 16 and 20
Secondary	Titers for Anti-herpes Simplex Virus (Anti-HSV) Neutralizing Antibodies.	Titers for Anti-HSV neutralizing antibodies are presented as Geometric Mean Titers (GMTs), and are expressed in Estimated Doses (ED), that is, the reciprocal of the dilution necessary to achieve neutralization. Antibody titers below the lowest level of quantification were not calculated .	At Months 0, 2, 6, 7, 12, 16 and 20
Secondary	Number of Subjects Reporting Solicited Local and General Symptoms	Solicited local symptoms assessed were pain, redness and swelling.; Solicited general symptoms assessed were fatigue, headache, malaise and fever (defined as oral/axillary/tympanic temperature equal to or above 37.5 degrees Celsius).	Within 7 days (Days 0-6) after vaccination
Secondary	Number of Subjects Reporting Grade 3 Solicited Local Symptoms	Solicited local symptoms assessed were pain, redness and swelling.; Grade 3 pain = pain that prevented normal activities.; Grade 3 redness/swelling = redness/swelling above 30 mm and persisting for more than 24 hours	Within 7 days (Days 0-6) after vaccination
Secondary	Number of Subjects Reporting Grade 3 and Related Solicited General Symptoms	Solicited general symptoms assessed were fatigue, headache, malaise and fever (oral/axillary/tympanic).; Grade 3 headache, fatigue, malaise = symptom that prevented normal activities.; Grade 3 fever = temperature above 39.0 degrees Celsius.; Related = symptom assessed by the investigator as causally related to the vaccination	Within 7 days (Days 0-6) after vaccination
Secondary	Number of Subjects Reporting Unsolicited Adverse Events (AEs)	Unsolicited AEs have been tabulated for a 31-day period. An unsolicited AE was any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.	Within 31 days after vaccination
Secondary	Number of Subjects With New Onset Chronic Diseases (NOCDs), Medically Significant Conditions (MSCs) and Serious Adverse Events (SAEs)	NOCDs included adverse events (AEs) as autoimmune disorders, asthma, type I diabetes, allergies. MSCs included AEs prompting emergency room or physician visits unrelated to common diseases or routine visits for physical examination or vaccination, or SAEs unrelated to common diseases. SAEs included medical occurrences either life-threatening, requiring hospitalization, or resulting in death, disability/incapacity or congenital anomaly/birth defect in a subject's offspring. Common diseases included upper respiratory infections (URIs), sinusitis, pharyngitis, gastroenteritis, urinary tract infection, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. The following were not reported if not considered as SAEs and occurring more than 30 days post vaccination: URIs, sinusitis, pharyngitis, gastroenteritis, injury, or visits for routine physical examination or vaccination. AEs are described, using Medical Dictionary for Regulatory Activities' preferred terms.	Throughout the study (From Month 0 up to Month 20)
Secondary	Number of Subjects Reporting Serious Adverse Events (SAEs)	SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in a subject's offspring.	Throughout the study (From Month 0 up to Month 20)