Clinical trial NCT00224484: Safety Study of Herpes Simplex Vaccine in HSV Seronegative and Seropositive Females Between 10 and 17 Years Old
Official title: A Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline Biologicals' Herpes Simplex Candidate Vaccine (gD2-AS04) in Healthy HSV Seronegative and Seropositive Female Subjects Aged 10-17 Years.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Herpes Simplex
Keywords: Herpes Simplex vaccine
Safety
Adolescents
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-23
Enrollment: 5960
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: Main goal of this study is to compare the occurrence of serious adverse events (SAEs) between the herpes simplex (gD2-AS04) vaccine group and the Saline control group throughout the study period (up to month 12).

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed description: Three groups of females (3000, 1500 and 1500 subjects, respectively) were injected 3 times (at months 0, 1 and 6) with the herpes simplex vaccine, the HavrixTM vaccine (control) and a Saline solution (placebo), respectively. Subjects were followed over 18 months.

Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that can and will comply with the requirements of the protocol should be enrolled in the study.
* Healthy female between, and including, 10 and 17 years of age at the time of the first vaccination.
* 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.
* Subjects must have a negative urine pregnancy test.
* Subjects of childbearing potential at the time of study entry must be abstinent or must be using an effective method of birth control for 30 days prior to vaccination 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.

Exclusion Criteria:

* Use of any investigational or non-registered product (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.
* Pregnant or lactating female.
* Female planning to become pregnant or likely to become pregnant during the first eight months of the study (months 0-8).
* Any previous confirmed history of, or current clinical signs or symptoms of, oro labial herpes (cold sores), herpetic whitlow or genital herpes disease, such as swelling, papules, vesicles, pustules, ulcers, crusts, fissures, erythema, discharge, dysuria or pain, burning, itching, tingling in the ano-genital area.
* History of previous or planned vaccination against hepatitis A or a history of hepatitis A infection.
* Previous vaccination against herpes.
* History of herpetic keratitis.
* History of multiform erythema.
* Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days 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 and 30 days after the first dose of study vaccine.
* 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 based on medical history and physical examination
* History of a current acute or chronic autoimmune disease.
* History of any neurological 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
* Acute disease at the time of enrolment
* Oral temperature \>= 37.5°C (99.5°F) / axillary temperature \>= 37.5°C (99.5°F) 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.
* 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: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Month 0 to Month 12
Secondary outcomes:
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after each and any vaccination
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after each and any vaccination
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: Within 30 days (Day 0-29) after any vaccination
measure: Number of Subjects With Unsolicited Adverse Events (AEs) With Medically Attended Visits
timeFrame: Within the 30 Day (Day 0-29) post-vaccination period
measure: Number of Subjects With New Onset Chronic Diseases (NOCD)
timeFrame: During the active phase (up to Month 12)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
timeFrame: At months 7 and 12
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
timeFrame: At months 7 and 12
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
timeFrame: At months 7 and 12
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
timeFrame: At months 7 and 12
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
timeFrame: At months 7 and 12
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
timeFrame: At months 7 and 12
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
timeFrame: At months 7 and 12
measure: Number of Subjects With Unsolicited Adverse Events (AEs) With Medically Attended Visits
timeFrame: Starting from Day 30 until the end of study (Month 18)
measure: Number of Subjects With Medically Significant Conditions (MSC)
timeFrame: During the Extended Safety Follow Up (ESFU) period (Month 12 to Month 18)
measure: Number of Subjects With New Onset Chronic Diseases (NOCD)
timeFrame: During the Extended Safety Follow Up (ESFU) period (Month 12 to Month 18)
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Up to month 18 (during active phase and ESFU period)
measure: Anti-glycoprotein D (Anti-gD) Antibody Concentrations
timeFrame: At months 0, 7 and 12
measure: Anti-deacylated Monophosphoryl Lipid A (Anti-MPL) Antibody Concentrations
timeFrame: At months 0, 7 and 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Birmingham
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state: Alabama
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state: Arizona
city: Mesa
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city: Tucson
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city: Beverly Hills
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city: Fountain Valley
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state: California
city: Long Beach
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state: California
city: Rolling Hills Estates
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state: California
city: Centennial
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facility: GSK Investigational Site
state: Colorado
city: Littleton
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state: Colorado
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state: Colorado
city: Westminster
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facility: GSK Investigational Site
state: Colorado
city: Wheat Ridge
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facility: GSK Investigational Site
state: Colorado
city: Norwich
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state: Connecticut
city: Clearwater
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state: Florida
city: Cocoa Beach
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facility: GSK Investigational Site
state: Florida
city: Melbourne
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facility: GSK Investigational Site
state: Florida
city: Naples
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facility: GSK Investigational Site
state: Florida
city: Chicago
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facility: GSK Investigational Site
state: Illinois
city: Arkansas City
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facility: GSK Investigational Site
state: Kansas
city: Wichita
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facility: GSK Investigational Site
state: Kansas
city: Towson
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facility: GSK Investigational Site
state: Maryland
city: Fridley
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facility: GSK Investigational Site
state: Minnesota
city: Saint Louis
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facility: GSK Investigational Site
state: Missouri
city: Saint Louis
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facility: GSK Investigational Site
state: Missouri
city: Whitehouse Station
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facility: GSK Investigational Site
state: New Jersey
city: Albuquerque
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facility: GSK Investigational Site
state: New Mexico
city: Bronx
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facility: GSK Investigational Site
state: New York
city: Bronx
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facility: GSK Investigational Site
state: New York
city: Stony Brook
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facility: GSK Investigational Site
state: New York
city: Raleigh
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facility: GSK Investigational Site
state: North Carolina
city: Sylva
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facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
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facility: GSK Investigational Site
state: North Carolina
city: Akron
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facility: GSK Investigational Site
state: Ohio
city: Cincinnati
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city: Cleveland
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city: Columbus
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state: Ohio
city: Columbus
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city: Hilliard
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facility: GSK Investigational Site
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city: Pickerington
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city: Westerville
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city: Erie
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city: Erie
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city: Pittsburgh
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facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
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city: Gray
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facility: GSK Investigational Site
state: Tennessee
city: Kingsport
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facility: GSK Investigational Site
state: Tennessee
city: Austin
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facility: GSK Investigational Site
state: Texas
city: Beaumont
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facility: GSK Investigational Site
state: Texas
city: Galveston
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facility: GSK Investigational Site
state: Texas
city: Lake Jackson
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facility: GSK Investigational Site
state: Texas
city: San Antonio
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state: Texas
city: Temple
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facility: GSK Investigational Site
state: Texas
city: Magna
country: United States
facility: GSK Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Salt Lake City
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facility: GSK Investigational Site
state: Utah
city: Sandy
country: United States
facility: GSK Investigational Site
state: Utah
city: West Jordan
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facility: GSK Investigational Site
state: Utah
city: West Jordan
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state: Utah
city: Norfolk
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facility: GSK Investigational Site
state: Virginia
city: Marshfield
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Garran
country: Australia
facility: GSK Investigational Site
state: Australian Capital Territory
city: Westmead
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: South Brisbane
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Hobart
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facility: GSK Investigational Site
state: Tasmania
city: Carlton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Wilrijk
country: Belgium
facility: GSK Investigational Site
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Surrey
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facility: GSK Investigational Site
state: British Columbia
city: Vancouver
country: Canada
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state: British Columbia
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Beauport
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facility: GSK Investigational Site
state: Quebec
city: Sainte-Foy
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Aarhus N
country: Denmark
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Château Renault
country: France
facility: GSK Investigational Site
city: Derval
country: France
facility: GSK Investigational Site
city: Evreux
country: France
facility: GSK Investigational Site
city: Haute Goulaine
country: France
facility: GSK Investigational Site
city: La Chapelle sur Erdre
country: France
facility: GSK Investigational Site
city: Le Temple De Bretagne
country: France
facility: GSK Investigational Site
city: Luynes
country: France
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city: Nantes
country: France
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city: Nantes
country: France
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city: Nort sur Erdre
country: France
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city: Paris
country: France
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city: Pont de L'Arche
country: France
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city: Saint Aubin des Chateaux
country: France
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city: Saint Avertin
country: France
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city: Saint Sebastien sur Loire
country: France
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city: Tours
country: France
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city: Athens
country: Greece
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city: Athens
country: Greece
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city: Komotini
country: Greece
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country: Greece
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country: Hungary
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city: Budapest
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country: Hungary
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city: Panevezys
country: Lithuania
facility: GSK Investigational Site
city: Vilnius
country: Lithuania
facility: GSK Investigational Site
city: Vilnius
country: Lithuania
facility: GSK Investigational Site
city: Vilnius
country: Lithuania
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Christchurch
country: New Zealand
facility: GSK Investigational Site
city: Bergen
country: Norway
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Blanes
country: Spain
facility: GSK Investigational Site
city: Castellon
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Montgat/Barcelona
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Karlskrona
country: Sweden
facility: GSK Investigational Site
city: Linköping
country: Sweden
facility: GSK Investigational Site
city: Malmö
country: Sweden
facility: GSK Investigational Site
city: Umeå
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
state: Hampshire
city: Blackpool
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: Blackpool
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: Blackpool
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: Bolton
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
state: Warwickshire
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
state: Warwickshire
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
state: West Midlands
city: Bradford
country: United Kingdom
facility: GSK Investigational Site
city: Doncaster
country: United Kingdom
facility: GSK Investigational Site
city: Leeds
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tavares F, Cheuvart B, Heineman T, Arellano F, Dubin G. Meta-analysis of pregnancy outcomes in pooled randomized trials on a prophylactic adjuvanted glycoprotein D subunit herpes simplex virus vaccine. Vaccine. 2013 Mar 25;31(13):1759-64. doi: 10.1016/j.vaccine.2013.01.002. Epub 2013 Jan 10.
citation: HSV-040 Study Group; Abu-Elyazeed RR, Heineman T, Dubin G, Fourneau M, Leroux-Roels I, Leroux-Roels G, Richardus JH, Ostergaard L, Diez-Domingo J, Poder A, Van Damme P, Romanowski B, Blatter M, Silfverdal SA, Berglund J, Josefsson A, Cunningham AL, Flodmark CE, Tragiannidis A, Dobson S, Olafsson J, Puig-Barbera J, Mendez M, Barton S, Bernstein D, Mares J, Ratner P. Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial. Vaccine. 2013 Dec 9;31(51):6136-43. doi: 10.1016/j.vaccine.2013.06.081. Epub 2013 Jul 9.
citation: Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008 Dec 2;26(51):6630-8. doi: 10.1016/j.vaccine.2008.09.049.