Infections, Papillomavirus
Conditions
Keywords
HPV vaccine,, Cervical cancer, Human papillomavirus infection,
Brief summary
A phase I, open label, single-centre study to evaluate the safety and immunogenicity of GlaxoSmithKline Biologicals' HPV -16/18 L1 VLP AS04 vaccine (GSK 580299, Cervarix TM), administered intramuscularly according to a 0, 1, 6-month schedule in healthy Chinese female subjects aged 15 - 45 years. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed description
The rationale for the protocol posting amendment was to change the study population from 18-35 to 15-45 years and to allow subjects who were administered routine vaccines e.g. Hepatitis A&B vaccines, meningococcal vaccines, Tetanus vaccine, Diphteria Tetanus Pertussis etc. up to 8 days before each HPV dose.
Interventions
BIOLOGICALGSK580299 (Cervarix™ , HPV -16/18 L1 VLP AS04 vaccine)
Intramuscular injection, 3 doses
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
15 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * A female of Chinese origin, residing in China, aged between 15 - 45 years (inclusive) at the time of the first vaccination. * Written informed consent obtained from the subject. For subjects below the legal age of consent, written informed consent must be obtained from the subject's parent or Legally Acceptable Representative (LAR), and written informed assent must be obtained from the subject. * Healthy subjects as established by medical history and clinical examination before entering into the study. * Subjects must have a negative urine pregnancy test. * Subjects must be of non-childbearing potential, or if the subject is of childbearing potential, she must be abstinent or must be using adequate contraception for 30 days prior to vaccination and continue for 2 months after completion of the vaccination series.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. * Pregnant or breastfeeding. * Planning to become pregnant or likely to become pregnant * 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. * Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days preceding and 30 days after the first dose of vaccine. Administration of some routine vaccines up to 8 days before the first dose of study vaccine is allowed. * Previous administration of components of the investigational vaccine. * Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination * History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccine. * Hypersensitivity to latex. * Major congenital defects or serious chronic illness. * History of any neurologic disorders or seizures. * Known acute or chronic, clinically significant system conditions. * Cancer or autoimmune disease under treatment. * Acute disease at the time of enrolment. * History of chronic alcohol consumption and/or drug abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Serious Adverse Events | Throughout the study period (up to Month 7) | Serious adverse events are defined as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
| Number of Subjects Reporting Solicited Local Symptoms | During the 7-day (Day 0-6) period following each vaccination | Solicited local symptoms assessed include pain, redness and swelling. |
| Number of Subjects Reporting Solicited General Symptoms | During the 7-day (Day 0-6) period following each vaccination | Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria. |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | Within 30 days (Day 0-29) after any vaccination | An unsolicited adverse event is defined as any adverse event (AE) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. |
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | At Month 0 and Month 7 | Hematological and biochemical parameters assessed in blood samples include alanine aminotransferase (ALT), basophils, creatinine, eosinophils, hematocrit, lymphocytes, monocytes, neutrophils, platelets, red blood cell, and white blood cells. Abnormalities reported include values outside the normal ranges: values higher than normal are designated as Above and values lower than normal as Below. |
| Number of Subjects Reporting Medically Significant Adverse Events | Throughout the study period (up to Month7) | Medically significant AEs were defined as AEs prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group Subjects received 3 doses of GSK580299 vaccine (Cervarix™, HPV -16/18 L1 VLP AS04 vaccine) according to a 0, 1, 6-month schedule. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Cervarix Group |
|---|---|
| Age, Continuous | 28.0 years STANDARD_DEVIATION 9.03 |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 30 |
| serious Total, serious adverse events | 1 / 30 |
Outcome results
Primary
Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters
Hematological and biochemical parameters assessed in blood samples include alanine aminotransferase (ALT), basophils, creatinine, eosinophils, hematocrit, lymphocytes, monocytes, neutrophils, platelets, red blood cell, and white blood cells. Abnormalities reported include values outside the normal ranges: values higher than normal are designated as Above and values lower than normal as Below.
Time frame: At Month 0 and Month 7
Population: Analysis was performed on subjects from the Total vaccinated cohort that completed the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | White blood cells Above [Month 0] | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | ALT Above [Month 0] | 3 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | ALT Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | ALT Above [Month 7] | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | ALT Below [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Basophils Above [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Basophils Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Basophils Above [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Basophils Below [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Creatinine Above [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Creatinine Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Creatinine Above [Month 7] | 3 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Creatinine Below [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Eosinophils Above [Month 0] | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Eosinophils Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Eosinophils Above [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Eosinophils Below [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Hematocrit Above [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Hematocrit Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Hematocrit Above [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Hematocrit Below [Month 7] | 13 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Lymphocytes Above [Month 0] | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Lymphocytes Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Lymphocytes Above [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Lymphocytes Below [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Monocytes Above [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Monocytes Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Monocytes Above [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Monocytes Below [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Neutrophils Above [Month 0] | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Neutrophils Below [Month 0] | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Neutrophils Above [Month 7] | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Neutrophils Below [Month 7] | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Platelets Above [Month 0] | 3 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Platelets Below [Month 0] | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Platelets Above [Month 7] | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Platelets Below [Month 7] | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Red blood cells Above [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Red blood cells Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Red blood cells Above [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | Red blood cells Below [Month 7] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | White blood cells Below [Month 0] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | White blood cells Above [Month 7] | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Hematological Parameters | White blood cells Below [Month 7] | 1 Participants |
Primary
Number of Subjects Reporting Medically Significant Adverse Events
Medically significant AEs were defined as AEs prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Throughout the study period (up to Month7)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Medically Significant Adverse Events | 2 Participants |
Primary
Number of Subjects Reporting Serious Adverse Events
Serious adverse events are defined as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: Throughout the study period (up to Month 7)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Serious Adverse Events | 1 Participants |
Primary
Number of Subjects Reporting Solicited General Symptoms
Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria.
Time frame: During the 7-day (Day 0-6) period following each vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Solicited General Symptoms | Arthralgia | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited General Symptoms | Fatigue | 10 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited General Symptoms | Axillary fever greater than 37 degrees Celcius | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited General Symptoms | Gastrointestinal symptoms | 4 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited General Symptoms | Headache | 8 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited General Symptoms | Myalgia | 7 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited General Symptoms | Rash | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited General Symptoms | Urticaria | 0 Participants |
Primary
Number of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed include pain, redness and swelling.
Time frame: During the 7-day (Day 0-6) period following each vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 26 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 16 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 9 Participants |
Primary
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
An unsolicited adverse event is defined as any adverse event (AE) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Time frame: Within 30 days (Day 0-29) after any vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 4 Participants |