Follow-up Study to Evaluate the Long-term Efficacy of the HPV Vaccine (580299) in Healthy Young Adult Women in Brazil

This study has been completed.

Sponsor:

Information provided by:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00518336

First received: August 17, 2007

Last updated: November 10, 2011

Last verified: November 2011

History of Changes

Results First Received: July 12, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Conditions:	HPV-16/18 Infections Cervical Neoplasia
Interventions:	Procedure: Blood sampling Procedure: Collection of cervical specimen

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of the five subjects withdraw at Year 7, three subjects came back during Year 8 and are therefore not longer considered as withdraw subjects. At Year 9, one subject, who did not participate to Year 7 and Year 8 visits, came back for one of the visits and was added to Total cohort.

Reporting Groups

	Description
Cervarix Group	Young adult women from the Brazilian cohort who participated in the primary study 580299/001 (NCT00689741) and follow-up study 580299/007 (NCT00120848) and received 3 doses of Cervarix at 0, 1 and 6 months intramuscularly into the deltoid region of the non-dominant arm during the primary study.
Placebo Group	Young adult women from the Brazilian cohort who participated in the primary study 580299/001 (NCT00689741) and follow-up study 580299/007 (NCT00120848) and received 3 doses of placebo at 0, 1 and 6 months intramuscularly into the deltoid region of the non-dominant arm during the primary study.

Participant Flow for 3 periods

Period 1: Year 7

	Cervarix Group	Placebo Group
STARTED	222	211
COMPLETED	220	208
NOT COMPLETED	2	3
Lost to Follow-up	2	0
Could not attend in time	0	3

Period 2: Year 8

	Cervarix Group	Placebo Group
STARTED	223 ^[1]	213 ^[2]
COMPLETED	222	211
NOT COMPLETED	1	2
Lost to Follow-up	1	1
Could not attend in time	0	1

[1]	1 subject withdrawn at Year 7 came back and was therefore no longer considered as withdrawn.
[2]	2 subjects withdrawn at Year 7 came back and were therefore no longer considered as withdrawn.

Period 3: Year 9

	Cervarix Group	Placebo Group
STARTED	224 ^[1]	213
COMPLETED	219	212
NOT COMPLETED	5	1
Migrated/moved from study area	1	1
Lost to Follow-up	3	0
Personal reasons	1	0

[1]	1 subject did not particpate at the previous timepoint, came back and was added in the Total cohort

Baseline Characteristics

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Reporting Groups

	Description
Cervarix Group	Young adult women from the Brazilian cohort who participated in the primary study 580299/001 (NCT00689741) and follow-up study 580299/007 (NCT00120848) and received 3 doses of Cervarix at 0, 1 and 6 months intramuscularly into the deltoid region of the non-dominant arm during the primary study.
Placebo Group	Young adult women from the Brazilian cohort who participated in the primary study 580299/001 (NCT00689741) and follow-up study 580299/007 (NCT00120848) and received 3 doses of placebo at 0, 1 and 6 months intramuscularly into the deltoid region of the non-dominant arm during the primary study.
Total	Total of all reporting groups

Baseline Measures

	Cervarix Group	Placebo Group	Total
Number of Participants [units: participants]	222	211	433
Age [units: years] Mean ± Standard Deviation	26.5 ± 3.2	26.4 ± 2.9	26.5 ± 3.05
Gender [units: participants]
Female	222	211	433
Male	0	0	0

Outcome Measures

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1. Primary:

Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and/or HPV-18 [ Time Frame: Up to year 8 ]

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2. Primary:

Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and/or HPV-18 [ Time Frame: Up to year 9 ]

Show Outcome Measure 2

3. Primary:

Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and /or HPV-18 [ Time Frame: Up to year 7 ]

Show Outcome Measure 3

4. Secondary:

Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type [ Time Frame: Up to year 8 ]

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5. Secondary:

Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type [ Time Frame: Up to year 8 ]

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6. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18 [ Time Frame: Up to year 8 ]

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7. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Types [ Time Frame: Up to year 8 ]

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8. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types [ Time Frame: Up to year 8 ]

Show Outcome Measure 8

9. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18 [ Time Frame: Up to year 8 ]

Show Outcome Measure 9

10. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Types [ Time Frame: Up to year 8 ]

Show Outcome Measure 10

11. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types [ Time Frame: Up to year 8 ]

Show Outcome Measure 11

12. Secondary:

Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 8 ]

Show Outcome Measure 12

13. Secondary:

Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 8 ]

Show Outcome Measure 13

14. Secondary:

Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 8 ]

Show Outcome Measure 14

15. Secondary:

Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 8 ]

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16. Secondary:

Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 8 ]

Show Outcome Measure 16

17. Secondary:

Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 8 ]

Show Outcome Measure 17

18. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With an HPV 16 and/or HPV-18 Cervical Infection [ Time Frame: Up to year 8 ]

Show Outcome Measure 18

19. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Oncogenic HPV Types Cervical Infection [ Time Frame: Up to year 8 ]

Show Outcome Measure 19

20. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection [ Time Frame: Up to year 8 ]

Show Outcome Measure 20

21. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With an HPV 16 and/or HPV-18 Cervical Infection [ Time Frame: Up to year 8 ]

Show Outcome Measure 21

22. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection [ Time Frame: Up to year 8 ]

Show Outcome Measure 22

23. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection [ Time Frame: Up to year 8 ]

Show Outcome Measure 23

24. Secondary:

Anti-HPV-16 and Anti-HPV-18 Enzyme-linked Immunosorbent Assay (ELISA) Titers in the Immunogenicity Cohort [ Time Frame: At Months 77-101 ]

Show Outcome Measure 24

25. Secondary:

Anti-HPV-16 and Anti-HPV-18 Pseudovirion-based Neutralization Assay (PBNA) Titers in the Immunogenicity Subset [ Time Frame: At Months 77-101 ]

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26. Secondary:

Number of Subjects With New Onset Chronic Diseases (NOCD) up to Year 7 [ Time Frame: Up to year 7 ]

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27. Secondary:

Number of Subjects With NOCD up to Year 8 [ Time Frame: Up to year 8 ]

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28. Secondary:

Number of Subjects With New Onset Autoimmune Disease (NOAD) up to Year 7 [ Time Frame: Up to year 7 ]

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29. Secondary:

Number of Subjects With NOAD up to Year 8 [ Time Frame: Up to year 8 ]

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30. Secondary:

Number of Subjects With Medically Significant Conditions up to Year 7 [ Time Frame: Up to year 7 ]

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31. Secondary:

Number of Subjects With Medically Significant Conditions up to Year 8 [ Time Frame: up to year 8 ]

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32. Secondary:

Number of Subjects With Serious Adverse Events (SAEs) up to Year 7 [ Time Frame: Up to year 7 ]

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33. Secondary:

Number of Subjects With SAEs up to Year 8 [ Time Frame: up to year 8 ]

Show Outcome Measure 33

34. Secondary:

Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type. [ Time Frame: Up to year 9 ]

Show Outcome Measure 34

35. Secondary:

Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type [ Time Frame: Up to year 9 ]

Show Outcome Measure 35

36. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18 [ Time Frame: Up to year 9 ]

Show Outcome Measure 36

37. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Type [ Time Frame: Up to year 9 ]

Show Outcome Measure 37

38. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types [ Time Frame: Up to year 9 ]

Show Outcome Measure 38

39. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18 [ Time Frame: Up to year 9 ]

Show Outcome Measure 39

40. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Types [ Time Frame: Up to year 9 ]

Show Outcome Measure 40

41. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types [ Time Frame: Up to year 9 ]

Show Outcome Measure 41

42. Secondary:

Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 9 ]

Show Outcome Measure 42

43. Secondary:

Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 9 ]

Show Outcome Measure 43

44. Secondary:

Show Outcome Measure 44

45. Secondary:

Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 9 ]

Show Outcome Measure 45

46. Secondary:

Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 9 ]

Show Outcome Measure 46

47. Secondary:

Show Outcome Measure 47

48. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With an HPV 16 and/or HPV-18 Cervical Infection [ Time Frame: Up to year 9 ]

Show Outcome Measure 48

49. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With Oncogenic HPV Types Cervical Infection [ Time Frame: Up to year 9 ]

Show Outcome Measure 49

50. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection [ Time Frame: Up to year 9 ]

Show Outcome Measure 50

51. Secondary:

Show Outcome Measure 51

52. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection [ Time Frame: Up to year 9 ]

Show Outcome Measure 52

53. Secondary:

Show Outcome Measure 53

54. Secondary:

Anti-HPV-16 and Anti-HPV-18 Enzyme-linked Immunosorbent Assay (ELISA) Titers in the Immunogenicity Cohort [ Time Frame: At Month 77 until year 9 (Month 113) ]

Show Outcome Measure 54

55. Secondary:

Anti-HPV-16 and Anti-HPV-18 Pseudovirion-based Neutralization Assay (PBNA) Titers in the Immunogenicity Subset [ Time Frame: At Month 77 until year 9 (Month 113) ]

Show Outcome Measure 55

56. Secondary:

Number of Subjects With New Onset Chronic Diseases (NOCD) up to Year 9 [ Time Frame: Up to year 9 ]

Show Outcome Measure 56

57. Secondary:

Number of Subjects With New Onset Autoimmune Disease (NOAD) up to Year 9. [ Time Frame: Up to year 9 ]

Show Outcome Measure 57

58. Secondary:

Number of Subjects With Medically Signifant Conditions up to Year 9 [ Time Frame: Up to year 9 ]

Show Outcome Measure 58

59. Secondary:

Number of Subjects With Serious Adverse Events (SAEs) up to Year 9. [ Time Frame: up to year 9 ]

Show Outcome Measure 59

60. Secondary:

Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type. [ Time Frame: Up to year 7 ]

Show Outcome Measure 60

61. Secondary:

Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type. [ Time Frame: Up to year 7 ]

Show Outcome Measure 61

62. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18 [ Time Frame: Up to year 7 ]

Show Outcome Measure 62

63. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Type [ Time Frame: Up to year 7 ]

Show Outcome Measure 63

64. Secondary:

Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types [ Time Frame: Up to year 7 ]

Show Outcome Measure 64

65. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18 [ Time Frame: Up to year 7 ]

Show Outcome Measure 65

66. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Type [ Time Frame: Up to year 7 ]

Show Outcome Measure 66

67. Secondary:

Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types [ Time Frame: Up to year 7 ]

Show Outcome Measure 67

68. Secondary:

Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 7 ]

Show Outcome Measure 68

69. Secondary:

Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 7 ]

Show Outcome Measure 69

70. Secondary:

Show Outcome Measure 70

71. Secondary:

Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 7 ]

Show Outcome Measure 71

72. Secondary:

Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to year 7 ]

Show Outcome Measure 72

73. Secondary:

Show Outcome Measure 73

74. Secondary:

Show Outcome Measure 74

75. Secondary:

Show Outcome Measure 75

76. Secondary:

Show Outcome Measure 76

77. Secondary:

Show Outcome Measure 77

78. Secondary:

Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection [ Time Frame: Up to year 7 ]

Hide Outcome Measure 78

Measure Type	Secondary
Measure Title	Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection
Measure Description	Abnormal cytology included ASC-US, LSIL, HSIL, AGC, and ASC-H. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time Frame	Up to year 7
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analyses was performed on the Total Cohort, which included all enrolled subjects who came at the first visit and received at least one vaccine dose (Cervarix or Placebo)

Reporting Groups

	Description
Cervarix Group	Young adult women from the Brazilian cohort who participated in the primary study 580299/001 (NCT00689741) and follow-up study 580299/007 (NCT00120848) and received 3 doses of Cervarix at 0, 1 and 6 months intramuscularly into the deltoid region of the non-dominant arm during the primary study.
Placebo Group	Young adult women from the Brazilian cohort who participated in the primary study 580299/001 (NCT00689741) and follow-up study 580299/007 (NCT00120848) and received 3 doses of placebo at 0, 1 and 6 months intramuscularly into the deltoid region of the non-dominant arm during the primary study.

Measured Values

	Cervarix Group	Placebo Group
Number of Participants Analyzed [units: participants]	189	178
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection [units: Subjects]
Including HPV-16 or 18 (N=189;178)	2	6
Without HPV-16 or 18 (N=189;178)	2	6

No statistical analysis provided for Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection

79. Secondary:

Show Outcome Measure 79

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Interim analysis at Year 7 and Year 8 are superseded by the final analysis at Year 9.

Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided by GlaxoSmithKline

Publications automatically indexed to this study:

Roteli-Martins CM, Naud P, De Borba P, Teixeira JC, De Carvalho NS, Zahaf T, Sanchez N, Geeraerts B, Descamps D. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012 Mar;8(3):390-7. doi: 10.4161/hv.18865. Epub 2012 Feb 13. PubMed PMID: 22327492.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00518336 History of Changes
Other Study ID Numbers:	109616 (Y7), 109624, 109625
Study First Received:	August 17, 2007
Results First Received:	July 12, 2010
Last Updated:	November 10, 2011
Health Authority:	Brazil: ANVISA United States: Food and Drug Administration

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