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NCT00250276

Evaluation of the Immune Responses of GSK Biologicals' HPV Vaccine Following Manufacturing Process Adaptation.

Completed Phase 3 Results posted Last updated 2 January 2020
What this trial tests

Phase 3 trial testing Cervarix™ in Infections, Papillomavirus in 798 participants. Completed in 1 March 2007.

Timeline
28 October 2005
Primary endpoint
1 March 2007
1 March 2007

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment798
Start date28 October 2005
Primary completion1 March 2007
Estimated completion1 March 2007
Sites8 locations across Denmark, Lithuania, Poland

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 25, female only, with Infections, Papillomavirus or Papillomavirus Vaccines. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Seroconverted (SCR) Subjects for Anti-Human Papillomavirus Type 16 (Anti-HPV-16) and Anti-Human Papillomavirus Type 18 (Anti-HPV-18) Primary · At Month 7

Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 concentrations ≥8 Enzyme-Linked Immunosorbent Assay \[ELISA\] units per milliliter \[EL.U/mL\] and anti-HPV-18 concentrations ≥7 EL.U/mL) in the serum of subjects seronegative before vaccination.

Anti-HPV-16
GroupValue95% CI
Cervarix Lot1 Group118
Cervarix Lot2 Group127
Cervarix Lot3 Group126
Pooled Group371
Cervarix Low Group102
Anti-HPV-18
GroupValue95% CI
Cervarix Lot1 Group129
Cervarix Lot2 Group143
Cervarix Lot3 Group135
Pooled Group407
Cervarix Low Group117
Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Primary · At Month 7

Seropositivity defined subjects with anti-HPV-16 antibody concentration ≥ 8 EL.U/mL and/or anti-HPV-18 antibody concentration ≥ 7 EL.U/mL.

Anti-HPV-16
GroupValue95% CI
Cervarix Lot1 Group54
Cervarix Lot2 Group38
Cervarix Lot3 Group43
Cervarix Low Group57
Anti-HPV-18
GroupValue95% CI
Cervarix Lot1 Group43
Cervarix Lot2 Group22
Cervarix Lot3 Group34
Cervarix Low Group41
Number of SCR Subjects for Anti-HPV-16 and Anti-HPV-18 Secondary · At Month 2

Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 concentrations ≥8 ELISA units per milliliter \[EL.U/mL\] and anti-HPV-18 concentrations ≥7 EL.U/mL) in the serum of subjects seronegative before vaccination.

Anti-HPV-16
GroupValue95% CI
Cervarix Lot1 Group117
Cervarix Lot2 Group126
Cervarix Lot3 Group125
Cervarix Low Group102
Anti-HPV-18
GroupValue95% CI
Cervarix Lot1 Group128
Cervarix Lot2 Group142
Cervarix Lot3 Group134
Cervarix Low Group116
Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Secondary · At Month 2

Seropositivity defined subjects with anti-HPV-16 antibody concentration ≥ 8 EL.U/mL and/or anti-HPV-18 antibody concentration ≥ 7 EL.U/mL .

Anti-HPV-16
GroupValue95% CI
Cervarix Lot1 Group54
Cervarix Lot2 Group38
Cervarix Lot3 Group43
Cervarix Low Group56
Anti-HPV-18
GroupValue95% CI
Cervarix Lot1 Group43
Cervarix Lot2 Group22
Cervarix Lot3 Group34
Cervarix Low Group41
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Secondary · During the 7-days (Day 0-6) post-vaccination

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) diameter of injection site.

Any Pain Dose 1
GroupValue95% CI
Cervarix Lot1 Group188
Cervarix Lot2 Group190
Cervarix Lot3 Group178
Pooled Group556
Cervarix Low Group185
Grade 3 Pain Dose 1
GroupValue95% CI
Cervarix Lot1 Group20
Cervarix Lot2 Group16
Cervarix Lot3 Group17
Pooled Group53
Cervarix Low Group12
Any Redness Dose 1
GroupValue95% CI
Cervarix Lot1 Group74
Cervarix Lot2 Group71
Cervarix Lot3 Group77
Pooled Group222
Cervarix Low Group75
Grade 3 Redness Dose 1
GroupValue95% CI
Cervarix Lot1 Group0
Cervarix Lot2 Group0
Cervarix Lot3 Group0
Pooled Group0
Cervarix Low Group0
Any Swelling Dose 1
GroupValue95% CI
Cervarix Lot1 Group58
Cervarix Lot2 Group57
Cervarix Lot3 Group57
Pooled Group172
Cervarix Low Group54
Grade 3 Swelling Dose 1
GroupValue95% CI
Cervarix Lot1 Group9
Cervarix Lot2 Group2
Cervarix Lot3 Group2
Pooled Group13
Cervarix Low Group4
Any Pain Dose 2
GroupValue95% CI
Cervarix Lot1 Group167
Cervarix Lot2 Group166
Cervarix Lot3 Group170
Pooled Group503
Cervarix Low Group161
Grade 3 Pain Dose 2
GroupValue95% CI
Cervarix Lot1 Group17
Cervarix Lot2 Group10
Cervarix Lot3 Group19
Pooled Group46
Cervarix Low Group12
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Secondary · During the 7-days (Day 0-6) post-vaccination

Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], gastro-intestinal, headache, myalgia, rash and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Arthralgia (joint pain) = pain occurring in joints that were distal from the injection site. This outcome presents solicited general symptoms post dose 1 of vac

Any Arthralgia
GroupValue95% CI
Cervarix Lot1 Group19
Cervarix Lot2 Group19
Cervarix Lot3 Group13
Pooled Group51
Cervarix Low Group17
Grade 3 Arthralgia
GroupValue95% CI
Cervarix Lot1 Group1
Cervarix Lot2 Group0
Cervarix Lot3 Group2
Pooled Group3
Cervarix Low Group0
Related Arthralgia
GroupValue95% CI
Cervarix Lot1 Group14
Cervarix Lot2 Group17
Cervarix Lot3 Group8
Pooled Group39
Cervarix Low Group14
Any Fatigue
GroupValue95% CI
Cervarix Lot1 Group81
Cervarix Lot2 Group84
Cervarix Lot3 Group73
Pooled Group238
Cervarix Low Group80
Grade 3 Fatigue
GroupValue95% CI
Cervarix Lot1 Group4
Cervarix Lot2 Group1
Cervarix Lot3 Group4
Pooled Group9
Cervarix Low Group5
Related Fatigue
GroupValue95% CI
Cervarix Lot1 Group60
Cervarix Lot2 Group62
Cervarix Lot3 Group48
Pooled Group170
Cervarix Low Group61
Any Fever
GroupValue95% CI
Cervarix Lot1 Group4
Cervarix Lot2 Group7
Cervarix Lot3 Group4
Pooled Group15
Cervarix Low Group5
Grade 3 Fever
GroupValue95% CI
Cervarix Lot1 Group0
Cervarix Lot2 Group0
Cervarix Lot3 Group0
Pooled Group0
Cervarix Low Group0
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Secondary · During the 7-days (Day 0-6) post-vaccination

Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], gastro-intestinal, headache, myalgia, rash and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Arthralgia (joint pain) = pain occurring in joints that were distal from the injection site. This outcome presents solicited general symptoms post dose 2 of vac

Any Arthralgia
GroupValue95% CI
Cervarix Lot1 Group14
Cervarix Lot2 Group14
Cervarix Lot3 Group14
Pooled Group42
Cervarix Low Group17
Grade 3 Arthralgia
GroupValue95% CI
Cervarix Lot1 Group0
Cervarix Lot2 Group0
Cervarix Lot3 Group1
Pooled Group1
Cervarix Low Group0
Related Arthralgia
GroupValue95% CI
Cervarix Lot1 Group12
Cervarix Lot2 Group11
Cervarix Lot3 Group10
Pooled Group33
Cervarix Low Group14
Any Fatigue
GroupValue95% CI
Cervarix Lot1 Group63
Cervarix Lot2 Group73
Cervarix Lot3 Group69
Pooled Group205
Cervarix Low Group58
Grade 3 Fatigue
GroupValue95% CI
Cervarix Lot1 Group2
Cervarix Lot2 Group4
Cervarix Lot3 Group3
Pooled Group9
Cervarix Low Group5
Related Fatigue
GroupValue95% CI
Cervarix Lot1 Group39
Cervarix Lot2 Group55
Cervarix Lot3 Group38
Pooled Group132
Cervarix Low Group40
Any Fever
GroupValue95% CI
Cervarix Lot1 Group7
Cervarix Lot2 Group5
Cervarix Lot3 Group7
Pooled Group19
Cervarix Low Group5
Grade 3 Fever
GroupValue95% CI
Cervarix Lot1 Group0
Cervarix Lot2 Group0
Cervarix Lot3 Group0
Pooled Group0
Cervarix Low Group0
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Secondary · During the 7-days (Day 0-6) post-vaccination

Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], gastro-intestinal, headache, myalgia, rash and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Arthralgia (joint pain) = pain occurring in joints that were distal from the injection site. This outcome presents solicited general symptoms post dose 3 of vac

Any Arthralgia
GroupValue95% CI
Cervarix Lot1 Group18
Cervarix Lot2 Group19
Cervarix Lot3 Group18
Pooled Group55
Cervarix Low Group13
Grade 3 Arthralgia
GroupValue95% CI
Cervarix Lot1 Group1
Cervarix Lot2 Group1
Cervarix Lot3 Group0
Pooled Group2
Cervarix Low Group0
Related Arthralgia
GroupValue95% CI
Cervarix Lot1 Group15
Cervarix Lot2 Group16
Cervarix Lot3 Group12
Pooled Group43
Cervarix Low Group11
Any Fatigue
GroupValue95% CI
Cervarix Lot1 Group76
Cervarix Lot2 Group67
Cervarix Lot3 Group64
Pooled Group207
Cervarix Low Group60
Grade 3 Fatigue
GroupValue95% CI
Cervarix Lot1 Group9
Cervarix Lot2 Group1
Cervarix Lot3 Group2
Pooled Group12
Cervarix Low Group6
Related Fatigue
GroupValue95% CI
Cervarix Lot1 Group58
Cervarix Lot2 Group50
Cervarix Lot3 Group49
Pooled Group157
Cervarix Low Group49
Any Fever
GroupValue95% CI
Cervarix Lot1 Group7
Cervarix Lot2 Group6
Cervarix Lot3 Group4
Pooled Group17
Cervarix Low Group8
Grade 3 Fever
GroupValue95% CI
Cervarix Lot1 Group0
Cervarix Lot2 Group0
Cervarix Lot3 Group1
Pooled Group1
Cervarix Low Group0
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Secondary · During the 7-days (Day 0-6) post-vaccination

Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], gastro-intestinal, headache, myalgia, rash and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Arthralgia (joint pain) = pain occurring in joints that were distal from the injection site. This outcome presents results across vaccination doses for solicite

Any Arthralgia
GroupValue95% CI
Cervarix Lot1 Group38
Cervarix Lot2 Group40
Cervarix Lot3 Group32
Pooled Group110
Cervarix Low Group35
Grade 3 Arthralgia
GroupValue95% CI
Cervarix Lot1 Group2
Cervarix Lot2 Group1
Cervarix Lot3 Group2
Pooled Group5
Cervarix Low Group0
Related Arthralgia
GroupValue95% CI
Cervarix Lot1 Group31
Cervarix Lot2 Group32
Cervarix Lot3 Group22
Pooled Group85
Cervarix Low Group31
Any Fatigue
GroupValue95% CI
Cervarix Lot1 Group117
Cervarix Lot2 Group117
Cervarix Lot3 Group106
Pooled Group340
Cervarix Low Group105
Grade 3 Fatigue
GroupValue95% CI
Cervarix Lot1 Group13
Cervarix Lot2 Group6
Cervarix Lot3 Group8
Pooled Group27
Cervarix Low Group12
Related Fatigue
GroupValue95% CI
Cervarix Lot1 Group90
Cervarix Lot2 Group95
Cervarix Lot3 Group78
Pooled Group263
Cervarix Low Group90
Any Fever
GroupValue95% CI
Cervarix Lot1 Group16
Cervarix Lot2 Group18
Cervarix Lot3 Group14
Pooled Group48
Cervarix Low Group15
Grade 3 Fever
GroupValue95% CI
Cervarix Lot1 Group0
Cervarix Lot2 Group0
Cervarix Lot3 Group1
Pooled Group1
Cervarix Low Group0
Number of Subjects With New Onset Chronic Diseases (NOCDs) Secondary · From Month 0 to Month 7

NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.

GroupValue95% CI
Cervarix Lot1 Group3
Cervarix Lot2 Group4
Cervarix Lot3 Group7
Pooled Group14
Cervarix Low Group3
Number of Subjects With Medically Significant Adverse Events (MSAEs) Secondary · From Month 0 to Month 7

MSAEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.

GroupValue95% CI
Pooled Group71
Cervarix Low Group23
Number of Subjects With (NOCDs) Secondary · From Month 0 to Month 12

NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.

GroupValue95% CI
Cervarix Lot1 Group4
Cervarix Lot2 Group4
Cervarix Lot3 Group7
Pooled Group15
Cervarix Low Group3

Adverse events — posted to ClinicalTrials.gov

Time frame: Solicited local/general symptoms: during the 7-days (Day 0-6) post vaccination. AEs: during the 30-days (Day 0-29) post vaccination. SAEs throughout the whole study period (up to Month 12).. Reporting threshold: 4.9%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cervarix Lot1 Group
Serious: 6/199 (3%)
Deaths:
Cervarix Lot2 Group
Serious: 1/198 (1%)
Deaths:
Cervarix Lot3 Group
Serious: 2/201 (1%)
Deaths:
Pooled Group
Serious: 9/598 (2%)
Deaths:
Cervarix Low Group
Serious: 3/200 (2%)
Deaths:

Serious adverse events (12 terms)

ReactionSystemCervarix Lot1 GroupCervarix Lot2 GroupCervarix Lot3 GroupPooled GroupCervarix Low Group
AppendicitisInfections and infestations
Supraventricular tachycardiaCardiac disorders
Basedow's diseaseEndocrine disorders
Cerebral malariaInfections and infestations
Pelvic inflammatory diseaseInfections and infestations
TuberculosisInfections and infestations
Femur fractureInjury, poisoning and procedural complications
Road traffic accidentInjury, poisoning and procedural complications
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
SyncopeNervous system disorders
Abortion missedPregnancy, puerperium and perinatal conditions
Abortion spontaneousPregnancy, puerperium and perinatal conditions
Other adverse events (13 terms — click to expand)

ReactionSystemCervarix Lot1 GroupCervarix Lot2 GroupCervarix Lot3 GroupPooled GroupCervarix Low Group
PainGeneral disorders
RednessGeneral disorders
SwellingGeneral disorders
FatigueGeneral disorders
HeadacheGeneral disorders
MyalgiaGeneral disorders
GastrointestinalGeneral disorders
ArthralgiaGeneral disorders
Fever/(Axillary) (°C)General disorders
RashGeneral disorders
NasopharyngitisInfections and infestations
UrticariaGeneral disorders
Injection site pruritusGeneral disorders

Most-reported serious reactions: Appendicitis, Supraventricular tachycardia, Basedow's disease, Cerebral malaria, Pelvic inflammatory disease, Tuberculosis, Femur fracture, Road traffic accident.

Data from ClinicalTrials.gov NCT00250276 adverse events section.

Sponsor's own description

Human papillomavirus infection has clearly been recognized as the cause of cervical cancer. Indeed, the infection of the cervix by certain oncogenic types of HPV, if not cleared , can lead over time to cervical cancer in women . This study will compare the immune response induced by different lots of the HPV-16/18 L1/AS04 vaccine, following adjustments to the manufacturing process.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme.
    Angelo MG, David MP, Zima J, Baril L, et al · · 2014 · cited 72× · PMID 24644063 · DOI 10.1002/pds.3554

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00250276.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing