Clinical trial NCT00224471: Study to Compare Safety and Immunogenicity of Commercial Scale Consistency Lots of Herpes Simplex Vaccine
Official title: A Phase III, Double-blind, Randomized, Study to Compare: 1) the Immunogenicity and Safety of 3 Commercial Scale Consistency Lots of GlaxoSmithKline (GSK) Biologicals' Herpes Simplex Candidate Vaccine in Healthy HSV-1 and -2 Seronegative (HSV 1-/2-) Female Subjects Aged 10 - 17 Years, and 2) Vaccine Immunogenicity in Healthy HSV 1-/2- Females Aged 10 - 17 Years With Healthy HSV 1-/2- Adult Females
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Herpes Simplex
Keywords: Adolescents
Immunogenicity
Safety
Herpes Simplex vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-23
Enrollment: 671
Sex: FEMALE
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Evaluate, one month after the third dose, the lot-to-lot consistency of 3 different commercial scale production lots of the candidate vaccine in healthy HSV 1-/2- females aged 10-17 years, determined by ELISA. Absence in significant variation for both parameters among the tested lots was hypothesized.

Detailed description: At month 0, 1 and 6, 3 groups of 184 subjects received each 3 doses of herpes simplex vaccine lot A, B or C, respectively. The study took 14 months to complete, including screening, and 6 visits were required. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Eligibility criteria: Inclusion Criteria:

* Healthy female between, and including, 10 and 17 years of age at the time of the first vaccination.
* Seronegative for HSV-1 and HSV-2 at screening
* Written informed assent obtained from the subject and written informed consent obtained from a parent or legal guardian of the subject prior to enrolment. If the subject is above the legal age of consent in her country, written informed consent will only be obtained from the subject.
* Subject must have a negative urine pregnancy test.
* Subject must be of non-childbearing potential, i.e. pre-menarcheal, or if of childbearing potential she must be abstinent or must be using an effective method of birth control 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. Subjects who reach menarche during the study and therefore are of childbearing potential must agree to follow the same precautions.
* A subject who (or whose parents/guardian) the investigator believes can and will comply with the requirements of the protocol

Exclusion criteria:

* Pregnant or lactating female.
* Female planning to become pregnant during the first eight months of the study
* Any previous history of, or current clinical signs or symptoms of oro-labial (cold sores), 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.
* History of erythema multiforme.
* 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 before and after the first dose of study vaccine with the following exceptions: Administration of routine meningococcal, hepatitis B, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus containing 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
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
* History of a current acute or chronic autoimmune disease.
* History of any neurologic disorders or seizures, with the exception of a single febrile seizure during childhood.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history or physical examination.
* Acute disease at the time of enrolment
* Oral temperature ≥99.5°F (\> 37.5°C) / axillary temperature ≥99.5°F (\> 37.5°C) at the time of enrolment
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose or planned use during the study period
* 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.

Primary outcomes:
measure: Anti-gD antibody titre in the entire cohort (10-17 yrs)
timeFrame: At month 7
Secondary outcomes:
measure: Anti-gD antibody titre
timeFrame: At months 2 and 12
measure: Anti-HSV neutralizing antibodies
timeFrame: At months 2, 7 and 12
measure: Occurrence and intensity of solicited local symptoms. Resulting school absenteeism will also be evaluated.
timeFrame: Within 7 days after each vaccination
measure: Occurrence, intensity, relationship to vaccination and resulting school absenteeism of solicited general symptoms
timeFrame: Within 7 days after each vaccination
measure: Occurrence, intensity, relationship to vaccination and resulting school absenteeism of unsolicited adverse events
timeFrame: Within 30 days after any vaccination
measure: Occurrence of new onset chronic diseases and other medically significant conditions, regardless of causal relationship to vaccination and intensity
timeFrame: Throughout the study
measure: Occurrence and relationship to vaccination of SAEs
timeFrame: Throughout the study period
measure: Anti-gD antibody titre in sera from HSV-042 subjects and in an equally sized subset of sera from adults from study 208141/039
timeFrame: At month 7
measure: Seroconversion rate by anti-gD ELISA. in HSV-042 subjects and in an equally sized subset of adults from study 208141/039
timeFrame: At month 7
measure: In the event that a cell-mediated immune correlate of protection is identified in study 208141/039: assessment of the immune correlate of protection in a random subset of HBV-042 subjects
timeFrame: At months 0, 2, 7, and 12
Other outcomes:
Locations:
city: Mesa
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: Golden
country: United States
facility: GSK Investigational Site
state: Colorado
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Galveston
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Beauport
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: