HerpeVac Trial for Young Women

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00057330
First received: March 31, 2003
Last updated: May 9, 2013
Last verified: March 2013
  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 or SB208141, GSK Biologicals' glycoprotein D (gD)-Alum/3-deacylated form of Monophosphoryl Lipid A (MPL) candidate genital herpes vaccine
Biological: Havrix™, GlaxoSmithKline (GSK) Biologicals' licensed 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:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Newly Acquired Genital Herpes Disease, Caused by Either Herpes Simplex Virus (HSV)-1 or HSV-2 [ Time Frame: Between Months 2 and 20 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Subjects With Newly Acquired Genital Herpes Disease, Caused by Either Herpes Simplex Virus (HSV)-1 or HSV-2 [ Time Frame: Between Months 7 and 20 ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Newly Acquired Herpes Simplex Virus (HSV)-2 Infection Confirmed by Either Virus Culture or HSV-2 Seroconversion. [ Time Frame: Between Months 2 and 20 ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Newly Acquired Herpes Simplex Virus (HSV)-2 Infection Confirmed by Either Virus Culture or HSV-2 Seroconversion [ Time Frame: Between Months 7 and 20 ] [ Designated as safety issue: No ]
    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.

  • Concentrations for Anti-glycoprotein D (Anti-gD) Antibodies. [ Time Frame: At Months 0, 2, 6, 7, 12, 16 and 20 ] [ Designated as safety issue: No ]
    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

  • Titers for Anti-herpes Simplex Virus (Anti-HSV) Neutralizing Antibodies. [ Time Frame: At Months 0, 2, 6, 7, 12, 16 and 20 ] [ Designated as safety issue: No ]
    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 .

  • 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. 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.

  • Number of Subjects With New Onset Chronic Diseases (NOCDs), Medically Significant Conditions (MSCs) and Serious Adverse Events (SAEs) [ Time Frame: Throughout the study (From Month 0 up to Month 20) ] [ Designated as safety issue: No ]
    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.

  • 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 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.


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 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
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: Havrix™, GlaxoSmithKline (GSK) Biologicals' licensed 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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):
Responsible Party: GlaxoSmithKline
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: May 9, 2013
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
Monophosphoryl lipid A
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014