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| ID | Type | Description | Link |
|---|---|---|---|
| 2006_515 |
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Subjects received HPV 16 L1 VLP vaccine or placebo (1:1 ratio). Endpoints included efficacy, immunogenicity, and safety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | HPV 16 L1 VLP vaccine |
|
| 2 | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Comparator: HPV 16 L1 Vaccine | Biological | A 0.5 intramuscular injection given at Day 1, Month 2, and Month 6 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Persistent HPV 16 Infection | Cases of persistent infection were those with detection of HPV 16 by PCR (Polymerase chain reaction) on at least 2 consecutive visits at least 4 months apart; or detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1 (Cervical intraepithelial neoplasia), CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy; or detection of HPV 16 on a subject's last visit. | Through Month 48 |
| Incidence of HPV 16-related CIN1, CIN2 or C1N3 | Cases of HPV 16-related CIN1, CIN2 or CIN3 are those with detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1, CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy. | Through Month 48 |
| Serum Anti-HPV 16 Geometric Mean Titers | The limit of detection of the assay was 6 mMU/ml. Samples with titer below the limit of detection were assigned a value of 3 for calculation of GMT and confidence interval. GMTs and confidence limits below the limit of detection are shown as "6.0". | Month 7 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16394035 | Background | Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR, Wiley DJ, Alvarez FB, Bautista OM, Jansen KU, Barr E. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2006 Jan;107(1):18-27. doi: 10.1097/01.AOG.0000192397.41191.fb. | |
| 12444178 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | HPV 16 L1 VLP (Group 1) | The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 1 were vaccinated (at Day 1, Month 2, and Month 6) with HPV (Human Papillomavirus) 16 Virus-Like Particle (VLP) Vaccine. The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine from completion of the Vaccination Period at Month 7 through Month 48. (The Month 7 visit was to be scheduled to occur no earlier than 3 weeks and no later than 7 weeks following the Month 6 visit.) |
| FG001 | Placebo (Group 2) | The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2, and Month 6) with placebo. The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received placebo from completion of the Vaccination Period at Month 7 through Month 48. (The Month 7 visit was to be scheduled to occur no earlier than 3 weeks and no later than 7 weeks following the Month 6 visit.) |
| FG002 | Extension | This group includes 400 subjects who received Monovalent HPV 16 L1 VLP vaccine or placebo during the base study. This includes subjects who previously discontinued from the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Vaccination (Day 1 to Month 7) |
|
| ||||||||||||||||||||||||
| Follow-up (Month 7 Though Month 48) |
| |||||||||||||||||||||||||
| Extension |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | HPV 16 L1 VLP (Group 1) | The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 1 were vaccinated (at Day 1, Month 2, and Month 6) with HPV (Human Papillomavirus) 16 Virus-Like Particle (VLP) Vaccine. The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine from completion of the Vaccination Period at Month 7 through Month 48. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Persistent HPV 16 Infection | Cases of persistent infection were those with detection of HPV 16 by PCR (Polymerase chain reaction) on at least 2 consecutive visits at least 4 months apart; or detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1 (Cervical intraepithelial neoplasia), CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy; or detection of HPV 16 on a subject's last visit. | Per-protocol population: subjects must have no major protocol violations, must be seronegative to HPV 16 at Day 1 and PCR (Polymerase chain reaction) negative to HPV 16 through Month 7, and must provide follow-up data after Month 7 | Posted | Number | Incidence per 100 person-years | Through Month 48 |
|
Adverse events (AEs) were collected from Day 1 until Month 7. No non-serious AEs were collected and no Vaccination Report Card (VRCs) were used in the extension study, therefore no data is entered for that group in the Other Adverse Events table.
Subjects were observed for at least 20 minutes after each vaccination for any immediate reaction. Subjects were prompted to report temperatures and local (i.e., injection site) AEs for 5 days following each injection. Data on all other AEs were collected and recorded on the subject's vaccine report card for 14 days after each vaccination visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | HPV 16 L1 VLP (Group 1) | The number of subjects who actually received the vaccine material corresponding to the indicated vaccination group. There was one subject randomized to the HPV 16 L1 VLP vaccine group who received placebo and then discontinued study participation. There was 1 subject randomized to the placebo group who received one vaccination of HPV 16 L1 VLP vaccine and then discontinued study participation. These 2 subjects were included in the counts reported in the Adverse Event tables. There were 2 subjects randomized to the HPV 16 L1 VLP vaccine group and 2 subjects randomized to the placebo group and who received mixed vaccine material. These 4 subjects were not included in the counts reported in this table. Therefore, this table reports N=1191 (1193 minus 2) subjects vaccinated with HPV 16 L1 VLP vaccine and N=1196 (1198 minus 2) subjects vaccinated with placebo. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pericarditis | Cardiac disorders | MedDRA 12.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 12.0 | Non-systematic Assessment |
Of note, the number of subjects reported in the results posting is slightly different than that specified in the publication by Koutsky, et al (2002). The data provided here is based on final data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| ID | Term |
|---|---|
| D000068857 | Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 |
| ID | Term |
|---|---|
| D017778 | Vaccines, Combined |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| Comparator: Placebo | Biological | A 0.5 intramuscular placebo injection given at Day 1, Month 2, and Month 6 |
|
| Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, Chiacchierini LM, Jansen KU; Proof of Principle Study Investigators. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002 Nov 21;347(21):1645-51. doi: 10.1056/NEJMoa020586. |
| 18435868 | Background | Paavonen J; Future II Study Group. Baseline demographic characteristics of subjects enrolled in international quadrivalent HPV (types 6/11/16/18) vaccine clinical trials. Curr Med Res Opin. 2008 Jun;24(6):1623-34. doi: 10.1185/03007990802068151. Epub 2008 Apr 23. |
| 18313445 | Background | Barr E, Gause CK, Bautista OM, Railkar RA, Lupinacci LC, Insinga RP, Sings HL, Haupt RM. Impact of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine in a sexually active population of North American women. Am J Obstet Gynecol. 2008 Mar;198(3):261.e1-11. doi: 10.1016/j.ajog.2007.09.001. |
| 17544766 | Background | Ault KA; Future II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-1868. doi: 10.1016/S0140-6736(07)60852-6. |
| 17445955 | Background | Fraser C, Tomassini JE, Xi L, Golm G, Watson M, Giuliano AR, Barr E, Ault KA. Modeling the long-term antibody response of a human papillomavirus (HPV) virus-like particle (VLP) type 16 prophylactic vaccine. Vaccine. 2007 May 22;25(21):4324-33. doi: 10.1016/j.vaccine.2007.02.069. Epub 2007 Mar 12. |
| 41276263 | Derived | Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2. |
| 22277329 | Derived | Wiley DJ, Masongsong EV, Lu S, Heather L S, Salem B, Giuliano AR, Ault KA, Haupt RM, Brown DR. Behavioral and sociodemographic risk factors for serological and DNA evidence of HPV6, 11, 16, 18 infections. Cancer Epidemiol. 2012 Jun;36(3):e183-9. doi: 10.1016/j.canep.2011.12.007. Epub 2012 Jan 25. |
| Lost to Follow-up |
|
| Pregnancy |
|
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Other |
|
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
|
| BG001 | Placebo (Group 2) | The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2, and Month 6) with placebo. The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received placebo from completion of the Vaccination Period at Month 7 through Month 48. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| OG001 | Placebo (Group 2) | The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2, and Month 6) with placebo. The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received placebo from completion of the Vaccination Period at Month 7 through Month 48. |
|
|
|
| Primary | Incidence of HPV 16-related CIN1, CIN2 or C1N3 | Cases of HPV 16-related CIN1, CIN2 or CIN3 are those with detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1, CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy. | Per-protocol population: subjects must have no major protocol violations, must be seronegative to HPV 16 at Day 1 and PCR negative to HPV 16 through Month 7, and must provide follow-up data after Month 7 | Posted | Number | Incidence per 100 person-years | Through Month 48 |
|
|
|
|
| Primary | Serum Anti-HPV 16 Geometric Mean Titers | The limit of detection of the assay was 6 mMU/ml. Samples with titer below the limit of detection were assigned a value of 3 for calculation of GMT and confidence interval. GMTs and confidence limits below the limit of detection are shown as "6.0". | Per-protocol population: subjects must have no major protocol violations, must be seronegative to HPV 16 at Day 1 and PCR negative to HPV 16 through Month 7, and must provide serology data at Month 7 | Posted | Geometric Mean | 95% Confidence Interval | milliMerck units/ml (mMU/ml) | Month 7 |
|
|
|
| 19 |
| 1,191 |
| 1,025 |
| 1,191 |
| EG001 | Placebo (Group 2) | The number of subjects who actually received the vaccine material corresponding to the indicated vaccination group. There was one subject randomized to the HPV 16 L1 VLP vaccine group who received placebo and then discontinued study participation. There was 1 subject randomized to the placebo group who received one vaccination of HPV 16 L1 VLP vaccine and then discontinued study participation. These 2 subjects were included in the counts reported in the Adverse Event tables. There were 2 subjects randomized to the HPV 16 L1 VLP vaccine group and 2 subjects randomized to the placebo group and who received mixed vaccine material. These 4 subjects were not included in the counts reported in this table. Therefore, this table reports N=1191 (1193 minus 2) subjects vaccinated with HPV 16 L1 VLP vaccine and N=1196 (1198 minus 2) subjects vaccinated with placebo. | 20 | 1,196 | 1,013 | 1,196 |
| EG002 | Extension | This group includes 400 subjects who received Monovalent HPV 16 L1 VLP vaccine or placebo during the base study. This includes subjects who previously discontinued from the study. | 1 | 400 | 0 | 0 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA 12.0 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 12.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 12.0 | Non-systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 12.0 | Non-systematic Assessment |
|
| Pyelonephritis acute | Infections and infestations | MedDRA 12.0 | Non-systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Back injury | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Multiple injuries | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Nerve injury | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Overdose | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Radial nerve injury | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Urinary bladder rupture | Injury, poisoning and procedural complications | MedDRA 12.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Limb deformity | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 12.0 | Non-systematic Assessment |
|
| Perineal laceration | Reproductive system and breast disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Aggression | Psychiatric disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Anxiety disorder | Psychiatric disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Bulimia nervosa | Psychiatric disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Completed suicide | Psychiatric disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Mania | Psychiatric disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Suicide attempt | Psychiatric disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Dysfunctional uterine bleeding | Reproductive system and breast disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Ovarian cyst | Reproductive system and breast disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Ovarian cyst ruptured | Reproductive system and breast disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 12.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Injection Site Erythema | General disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Injection Site Haematoma | General disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Injection Site Pain | General disorders | MedDRA 12.0 | Non-systematic Assessment |
|
| Injection Site Swelling | General disorders | MedDRA 12.0 | Non-systematic Assessment |
|
Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck 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.
| D053918 |
| Papillomavirus Vaccines |
| D014765 | Viral Vaccines |