Evaluation of the Safety and Immunogenicity of GSK Biologicals' HPV Vaccine 580299 When Administered in Healthy Females Aged 9 - 25 Years Using an Alternative Schedule and an Alternative Dosing as Compared to the Standard Schedule and Dosing
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Infections, Papillomavirus
- Sponsor
- GlaxoSmithKline
- Enrollment
- 961
- Locations
- 1
- Primary Endpoint
- Number of Subjects With Report of Any, and Grade 3 Solicited Local Symptoms
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
Human Papillomavirus (HPV) infection has been established as a necessary cause of cervical cancer. GlaxoSmithKline (GSK) Biologicals has developed an HPV vaccine (580299) which targets the 2 most common oncogenic HPV types (HPV-16 and HPV-18), found in approximately 70% of all cervical cancers. In previous trials this vaccine has been found to be efficacious in the prevention of incident and persistent HPV-16/18 infections and associated cytological abnormalities and cervical dysplasia. In this partially-blind study, GSK Biologicals will evaluate the safety and immunogenicity of the HPV vaccine using an alternative schedule and an alternative dosing when administered in healthy young females aged 9 to 25 years, as compared to the standard HPV vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. The protocol posting has been updated following a protocol amendment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects who the investigator believes that they and/or their parents can and will comply with the requirements of the protocol should be enrolled in the study.
- •A female subject between, and including, 9 and 25 years of age at the time of the first vaccination.
- •Written informed consent/assent obtained from the subject prior to enrolment. For subjects above the legal age of consent, written informed consent must be obtained from the subject. For subjects below the legal age of consent, written informed consent from the subject's parents/legally acceptable representative, and written informed assent must be obtained from the subject.
- •Healthy subjects as established by medical history and history-oriented clinical examination before entering into the study.
- •Subject must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series.
Exclusion Criteria
- •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 24).
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- •Concurrently participating in another clinical study, at any time during the study period (up to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
- •Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of vaccine. Planned administration/administration of routine vaccines, up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
- •Pregnant or breastfeeding female.
- •A woman planning to become pregnant or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose.
- •Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (up to Month 24).
- •Previous administration of components of the investigational vaccine.
- •Cancer or autoimmune disease under treatment.
- •Any medically diagnosed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
Arms & Interventions
Cervarix 1/Placebo Group
Subjects received 2 doses of the Cervarix vaccine, formulation 1, at Month 0 and Month 2, and 1 dose of placebo at Month 6. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Intervention: Placebo
Cervarix 1/Placebo Group
Subjects received 2 doses of the Cervarix vaccine, formulation 1, at Month 0 and Month 2, and 1 dose of placebo at Month 6. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Intervention: Cervarix
Cervarix 1/Placebo/Cervarix 1 Group
Subjects received 2 doses of the Cervarix vaccine, formulation 1, at Month 0 and Month 6, and 1 dose of placebo at Month 2. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Intervention: Cervarix
Cervarix 1/Placebo/Cervarix 1 Group
Subjects received 2 doses of the Cervarix vaccine, formulation 1, at Month 0 and Month 6, and 1 dose of placebo at Month 2. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Intervention: Placebo
Cervarix 2/Placebo/Cervarix 2 Group
Subjects received 2 doses of the Cervarix vaccine, formulation 2, at Month 0 and Month 6, and 1 dose of placebo at Month 2. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Intervention: Cervarix
Cervarix 2/Placebo/Cervarix 2 Group
Subjects received 2 doses of the Cervarix vaccine, formulation 2, at Month 0 and Month 6, and 1 dose of placebo at Month 2. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Intervention: Placebo
Cervarix 2 Group
Subjects received 3 doses of the Cervarix vaccine, formulation 2, at Month 0, Month 2 and Month 6. The Cervarix vaccine was administered intramuscularly into the deltoid of the non-dominant arm.
Intervention: Cervarix
Outcomes
Primary Outcomes
Number of Subjects With Report of Any, and Grade 3 Solicited Local Symptoms
Time Frame: Within 7 days (Day 0-6) after vaccination.
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the solicited local symptom irrespective of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling larger than (\>) 50 millimeters (mm).
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time Frame: Within 7 days (Day 0-6) after vaccination.
Assessed solicited general symptoms were arthralgia, fatigue, fever (defined as axillary temperature equal or above (≥) 37.5 degrees Celsius (°C), gastrointestinal symptoms, which included nausea, vomiting, diarrhoea and/or abdominal pain, headache, myalgia, rash and urticaria. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature ≥ 39 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related symptom = symptom assessed by the investigator to be causally related to vaccination.
Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies
Time Frame: One month after vaccination with the last dose of the Cervarix vaccine (Cervarix 1/Placebo Group: Month 3; Other groups: Month 7).
Titers are given as Geometric Mean Titers (GMTs) expressed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Secondary Outcomes
- Number of Subjects With New Onset of Chronic Diseases (NOCDs)(Throughout the study period, from Month 0 to Month 60.)
- Number of Subjects With Serious Adverse Events (SAEs).(From Month 0 to Month 48.)
- Number of Subjects With Serious Adverse Events (SAEs)(Throughout the study period, from Month 0 to Month 60.)
- Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies(At Month 60 of the safety follow-up phase)
- Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.(At Month 7 (M7))
- Number of Seroconverted Subjects Against Human Papillomavirus 16 (HPV-16) and Human Papillomavirus 18 (HPV-18)(At Month 60 of the safety follow-up phase)
- Number of Subjects With Pregnancy Outcomes.(Throughout the study period, from Month 0 to Month 60.)
- Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs).(Within 30 days (Day 0-29) after vaccination.)
- Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies .(At Month 3, 1 month after the second dose of vaccine or placebo)
- Number of Subjects With Medically Significant Conditions (MSCs).(Throughout the study period, from Month 0 to Month 60.)
- Number of Subjects With New Onset of Autoimmune Diseases (NOADs)(Throughout the study period, from Month 0 to Month 60.)
- Number of Subjects With New Onset of Autoimune Diseases (NOADs)(From Month 0 to Month 48.)