HerpeVac Trial for Young Women - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00057330

Purpose

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.

Condition	Intervention	Phase
Herpes Simplex Infection	Biological: HSV Vaccine Biological: Hepatitis A Vaccine	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Outcomes Assessor) Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: Genital Herpes Hepatitis Hepatitis A Herpes Simplex

Drug Information available for: Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Number of Subjects Reporting Genital Herpes Disease [ Time Frame: Between Months 2 and 20 ] [ Designated as safety issue: No ]
Genital herpes disease is defined as signs (swelling, papules, vesicles, ulcers, crusts, fissures, erythema, or vaginal discharge) and/or symptoms (pain, burning, itching, tingling, dysuria) which develop on the skin or mucosa of the anogenital region and/or buttocks and laboratory confirmation of HSV-1 or 2 infection (either concomitant positive HSV culture or HSV seroconversion within 6 months after onset of signs and/or symptoms).

Secondary Outcome Measures:

Number of Subjects Reporting Genital Herpes Disease [ Time Frame: Between Months 7 and 20 ] [ Designated as safety issue: No ]
Genital herpes disease is defined as signs (swelling, papules, vesicles, ulcers, crusts, fissures, erythema, or vaginal discharge) and/or symptoms (pain, burning, itching, tingling, dysuria) which develop on the skin or mucosa of the anogenital region and/or buttocks and laboratory confirmation of HSV-1 or 2 infection (either concomitant positive HSV culture or HSV seroconversion within 6 months after onset of signs and/or symptoms).
Number of Subjects Reporting Herpes Simplex Virus (HSV)-2 Infection [ Time Frame: Between Months 2 and 20 ] [ Designated as safety issue: No ]
HSV-2 infection was confirmed by either virus culture or HSV-2 seroconversion
Number of Subjects Reporting Herpes Simplex Virus (HSV)-2 Infection [ Time Frame: Between Months 7 and 20 ] [ Designated as safety issue: No ]
HSV-2 infection was confirmed by either virus culture or HSV-2 seroconversion
Anti-glycoprotein D (Anti-gD) Antibodies (By ELISA) [ Time Frame: At Months 0, 2, 6, 7, 12, 16 and 20 ] [ Designated as safety issue: No ]
These data will be updated when they become available.
HSV Neutralizing Antibodies [ Time Frame: At Months 0, 2, 6, 7, 12, 16 and 20 ] [ Designated as safety issue: No ]
These data will be updated when they become available.
Number of Subjects Reporting Solicited Local and General Symptoms [ Time Frame: Within 7 days (Days 0-6) after vaccination ] [ Designated as safety issue: No ]
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).
Number of Subjects Reporting Grade 3 Solicited Local Symptoms [ Time Frame: Within 7 days (Days 0-6) after vaccination ] [ Designated as safety issue: No ]
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
Number of Subjects Reporting Grade 3 and Related Solicited General Symptoms [ Time Frame: Within 7 days (Days 0-6) after vaccination ] [ Designated as safety issue: No ]
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
Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: Within 31 days after vaccination ] [ Designated as safety issue: No ]
Unsolicited AEs have been tabulated for a 31-day period

Unsolicited AE covers any AE 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.
Number of Subjects Reporting New Onset Chronic Disease (NOCDs), Serious Unsolicited Symptoms and Medically Significant Conditions (MSCs) [ Time Frame: Throughout the study (From Month 0 up to Month 20) ] [ Designated as safety issue: No ]
NOCDs include autoimmune disorders, asthma, type I diabetes. MSC include AEs prompting emergency room or physician visits that are not related to common diseases.

The following did not require reporting as long as they were not considered Serious Adverse Events (SAEs) and occur more than 30 days after each vaccination: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, injury, visits for routine physical examination or visits for vaccination.
Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: Throughout the study (From Month 0 up to Month 20) ] [ Designated as safety issue: No ]
SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

Enrollment:	8323
Study Start Date:	January 2003
Study Completion Date:	August 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Herpes Simplex Virus Group Females between, and including, 18 and 30 years of age at the time of first vaccination who received 3 doses of herpes simplex virus (HSV) vaccine intramuscularly in the non-dominant deltoid on a 0, 1, 6 month schedule.	Biological: HSV Vaccine the vaccine was administered intramuscularly in the non-dominant deltoid
Experimental: Havrix Group Females between, and including, 18 and 30 years of age at the time of first vaccination who received 3 doses of the investigational formulation of Havrix vaccine intramuscularly in the non-dominant deltoid on a 0, 1, 6 month schedule.	Biological: Hepatitis A Vaccine the vaccine was administered intramuscularly in the non-dominant deltoid

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years to 30 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Belshe RB, Leone PA, Bernstein DI, Wald A, Levin MJ, Stapleton JT, Gorfinkel I, Morrow RL, Ewell MG, Stokes-Riner A, Dubin G, Heineman TC, Schulte JM, Deal CD; Herpevac Trial for Women. Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med. 2012 Jan 5;366(1):34-43.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00057330 History of Changes
Other Study ID Numbers:	01-643, 208141/039
Study First Received:	March 31, 2003
Results First Received:	September 29, 2011
Last Updated:	January 31, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Herpes Simplex
Herpesviridae Infections
DNA Virus Infections
Virus Diseases

Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases

ClinicalTrials.gov processed this record on May 21, 2012