Trial Outcomes & Findings for A Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine/Cervarix TM Vaccine in Healthy Females Aged 15-25 Years (NCT NCT00485732)
NCT ID: NCT00485732
Last Updated: 2018-07-20
Results Overview
Seroconversion is defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.
COMPLETED
PHASE3
225 participants
One month post Dose 3 (Month 7)
2018-07-20
Participant Flow
Participant milestones
| Measure |
Cervarix Group
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Overall Study
STARTED
|
149
|
76
|
|
Overall Study
COMPLETED
|
141
|
67
|
|
Overall Study
NOT COMPLETED
|
8
|
9
|
Reasons for withdrawal
| Measure |
Cervarix Group
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
3
|
|
Overall Study
Withdrawal by Subject
|
5
|
4
|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
Baseline Characteristics
A Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine/Cervarix TM Vaccine in Healthy Females Aged 15-25 Years
Baseline characteristics by cohort
| Measure |
Cervarix Group
n=149 Participants
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=76 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
Total
n=225 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
22.0 years
STANDARD_DEVIATION 2.24 • n=5 Participants
|
21.9 years
STANDARD_DEVIATION 2.63 • n=7 Participants
|
22.0 years
STANDARD_DEVIATION 2.37 • n=5 Participants
|
|
Sex: Female, Male
Female
|
149 Participants
n=5 Participants
|
76 Participants
n=7 Participants
|
225 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: One month post Dose 3 (Month 7)Population: Analysis was performed on initially seronegative subjects from the According-to-Protocol (ATP) cohort for immunogenicity.
Seroconversion is defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.
Outcome measures
| Measure |
Cervarix Group
n=125 Participants
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=61 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
Anti-HPV-16
|
125 Participants
|
2 Participants
|
|
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
Anti-HPV-18
|
122 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Before vaccination (PRE) and one month post Dose 3 (Month 7)Population: Analysis was performed on the ATP cohort for immunogenicity.
Titres are given as geometric mean titres (GMTs) calculated on all subjects.
Outcome measures
| Measure |
Cervarix Group
n=136 Participants
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=67 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Anti-HPV-16 and Anti-HPV-18 Antibody Titres
Anti-HPV-16 (PRE)
|
4.6 titre
Interval 4.2 to 5.1
|
4.8 titre
Interval 4.1 to 5.7
|
|
Anti-HPV-16 and Anti-HPV-18 Antibody Titres
Anti-HPV-16 (Month 7)
|
9226.4 titre
Interval 8085.4 to 10528.4
|
4.9 titre
Interval 4.2 to 5.8
|
|
Anti-HPV-16 and Anti-HPV-18 Antibody Titres
Anti-HPV-18 (PRE)
|
4.1 titre
Interval 3.7 to 4.4
|
4.0 titre
Interval 3.5 to 4.5
|
|
Anti-HPV-16 and Anti-HPV-18 Antibody Titres
Anti-HPV-18 (Month 7)
|
4240.2 titre
Interval 3692.1 to 4869.7
|
4.3 titre
Interval 3.7 to 5.0
|
SECONDARY outcome
Timeframe: During the 7-day (Days 0-6) period following each vaccinationPopulation: Analysis was performed on the Total vaccinated cohort on the subjects with available data.
Solicited local symptoms assessed include pain, redness and swelling at the injection site.
Outcome measures
| Measure |
Cervarix Group
n=145 Participants
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=72 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Solicited Local Symptoms
Pain
|
140 Participants
|
64 Participants
|
|
Number of Subjects Reporting Solicited Local Symptoms
Redness
|
109 Participants
|
35 Participants
|
|
Number of Subjects Reporting Solicited Local Symptoms
Swelling
|
89 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: During the 7-day (Days 0-6) period following each vaccinationPopulation: Analysis was performed on the Total vaccinated cohort on the subjects with available data.
Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria.
Outcome measures
| Measure |
Cervarix Group
n=145 Participants
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=72 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Solicited General Symptoms
Arthralgia
|
35 Participants
|
8 Participants
|
|
Number of Subjects Reporting Solicited General Symptoms
Fatigue
|
103 Participants
|
39 Participants
|
|
Number of Subjects Reporting Solicited General Symptoms
Fever
|
7 Participants
|
2 Participants
|
|
Number of Subjects Reporting Solicited General Symptoms
Gastrointestinal symptoms
|
52 Participants
|
16 Participants
|
|
Number of Subjects Reporting Solicited General Symptoms
Headache
|
73 Participants
|
30 Participants
|
|
Number of Subjects Reporting Solicited General Symptoms
Myalgia
|
97 Participants
|
33 Participants
|
|
Number of Subjects Reporting Solicited General Symptoms
Rash
|
29 Participants
|
8 Participants
|
|
Number of Subjects Reporting Solicited General Symptoms
Urticaria
|
12 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: During the 30-day (Days 0-29) period following each vaccinationUnsolicited adverse event= 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.
Outcome measures
| Measure |
Cervarix Group
n=149 Participants
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=76 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Unsolicited Adverse Events (AE)
|
66 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: From Day 0 up to Month 7NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes. Medically significant AEs assessed include AEs prompting emergency room visits and physician office visits not related to common illnesses or Serious Adverse Events (SAEs) that are not related to common illnesses.
Outcome measures
| Measure |
Cervarix Group
n=149 Participants
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=76 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions
NOCD
|
5 Participants
|
6 Participants
|
|
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions
Medically Significant Conditions
|
34 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: From Day 0 up to Month 7Serious adverse events assessed include medical occurrences that result in death, is 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.
Outcome measures
| Measure |
Cervarix Group
n=149 Participants
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=76 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Serious Adverse Events (SAE)
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: from Day 0 up to Month 7Population: Analysis was performed on subjects with a pregnancy.
Total: the total number of pregnancies in a group. The specific outcomes are also listed.
Outcome measures
| Measure |
Cervarix Group
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=1 Participants
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Number of Subjects With Pregnancies and Their Outcome
Elective abortion
|
—
|
1 Participants
|
|
Number of Subjects With Pregnancies and Their Outcome
Total
|
—
|
1 Participants
|
Adverse Events
Cervarix Group
Placebo Group
Serious adverse events
| Measure |
Cervarix Group
n=149 participants at risk
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=76 participants at risk
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/149
|
1.3%
1/76
|
|
Reproductive system and breast disorders
Ovarian cyst ruptured
|
0.67%
1/149
|
0.00%
0/76
|
|
Infections and infestations
Pelvic inflammatory disease
|
0.67%
1/149
|
0.00%
0/76
|
Other adverse events
| Measure |
Cervarix Group
n=149 participants at risk
Subjects received 3 doses of HPV-16/18 VLP/AS04 vaccine (Cervarix TM) vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
|
Placebo Group
n=76 participants at risk
Subjects received 3 doses of placebo according to a 0, 1, 6-month schedule.
|
|---|---|---|
|
Infections and infestations
Upper respiratoy tract infection
|
13.4%
20/149
|
3.9%
3/76
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
8.7%
13/149
|
3.9%
3/76
|
|
Nervous system disorders
Headache
|
6.0%
9/149
|
5.3%
4/76
|
|
General disorders
Injection site pruritus
|
6.0%
9/149
|
0.00%
0/76
|
|
General disorders
Pain
|
94.0%
140/149
|
84.2%
64/76
|
|
General disorders
Redness
|
73.2%
109/149
|
46.1%
35/76
|
|
General disorders
Swelling
|
59.7%
89/149
|
25.0%
19/76
|
|
General disorders
Arthralgia
|
23.5%
35/149
|
10.5%
8/76
|
|
General disorders
Gastrointestinal symptoms
|
34.9%
52/149
|
21.1%
16/76
|
|
General disorders
Headache
|
49.0%
73/149
|
39.5%
30/76
|
|
General disorders
Myalgia
|
65.1%
97/149
|
43.4%
33/76
|
|
General disorders
Rash
|
19.5%
29/149
|
10.5%
8/76
|
|
General disorders
Urticaria
|
8.1%
12/149
|
2.6%
2/76
|
|
General disorders
Fatigue
|
69.1%
103/149
|
51.3%
39/76
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER