HPV 16 InfectionPhase 2NCT00365378

Study of Human Papillomavirus (HPV) 16 Vaccine in the Prevention of HPV 16 Infection in 16- to 23-Year-Old Females (V501-005)

A Phase 2 study testing Comparator: HPV 16 L1 Vaccine in people with HPV 16 Infection, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

Subjects received HPV 16 L1 VLP vaccine or placebo (1:1 ratio). Endpoints included efficacy, immunogenicity, and safety. Read more about this study

Who is it for?: Ages 16 to 23 years, women onlyHealthy volunteers can take part
Conditions the study is for: HPV 16 Infection
What is being tested?: Comparator: HPV 16 L1 Vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 2,409 participants
Where: No sites listed yet
Study dates: Sep 1999to Jul 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 to 23 years
Women only
Healthy volunteers accepted
Child, Adult

Who may be able to join

Healthy, unmarried females age 16 to 23 years with intact uteri
Not pregnant at enrollment
Agreed to use effective contraception through Month 7 of the study
A lifetime history of 0 to 5 male partners with whom the subjects engaged in at least one episode of insertive intercourse

Who cannot join

No prior history of Human Papillomavirus (HPV) vaccination
No receipt of any other vaccination within 1 month prior to enrollment or plans to receive any other vaccination within 1 month prior to or after any dose of study vaccine
No prior history of an abnormal Papanicolaou (Pap) test showing Squamous intraepithelial lesion (SIL) or biopsy showing Cervical intraepithelial neoplasia (CIN)

About this study

Official title: Study of Pilot Manufacturing Lot of HPV 16 Virus-Like Particle (VLP) Vaccine in the Prevention of HPV 16 Infection in 16- to 23-Year-Old Females

Subjects received HPV 16 L1 VLP vaccine or placebo (1:1 ratio). Endpoints included efficacy, immunogenicity, and safety.

Conditions: HPV 16 Infection
Being tested: Comparator: HPV 16 L1 Vaccine, Comparator: Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Comparator: HPV 16 L1 VaccineBiological
Also called V501
A 0.5 intramuscular injection given at Day 1, Month 2, and Month 6
Comparator: PlaceboBiological
A 0.5 intramuscular placebo injection given at Day 1, Month 2, and Month 6

Study groups in NCT00365378
Study group	Role	What they receive
1	Experimental	HPV 16 L1 VLP vaccine Receives: Biological: Comparator: HPV 16 L1 Vaccine
2	Placebo comparator	Placebo Receives: Biological: Comparator: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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".
Measured: Month 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 1999Jul 2009

First posted17 Aug 2006 (estimated)
Study startSep 1999
Primary completionMar 2004
Study completionJul 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for HPV 16 InfectionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 2,409 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00365378
Sponsor's protocol ID: V501-005
Other IDs: 2006_515
Status last verified: Oct 2015
First submitted: 16 Aug 2006
Last updated: 23 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 16394035
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.
PubMed 12444178
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.
PubMed 18435868
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.
PubMed 18313445
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.
PubMed 17544766
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.
PubMed 17445955
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.
PubMed 41276263
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.
PubMed 22277329

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer
Active, not recruitingPhase 4
An Exploratory Open-Label Clinical Trial Evaluating the Immunogenicity of the 9-valent 2-dose HPV Vaccination Regimen
HPV Infection
Active, not recruitingPhase 3
Efficacy Against Oral Persistent Infection, Immunogenicity and Safety of the 9-valent Human Papillomavirus Vaccine (9vHPV) in Men Aged 20-45 Years (V503-049)
Papillomavirus Infections
Recruiting
Multicenter Prospective Non-randomized Controlled Study of ALA-PDT for LSIL With HPV16/18 Infection
HPV-16/18, Photodynamic Therapy (PDT)
Not yet recruiting
Epidemiology of Anal Human Papillomavirus Carriage in Female Solid Organ Transplant Recipients With More Than 10 Years of Immunosuppression
Human Papillomavirus Infection, Anal HPV Infection

All HPV 16 Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Study of Pilot Manufacturing Lot of HPV 16 Virus-Like Particle (VLP) Vaccine in the Prevention of HPV 16 Infection in 16- to 23-Year-Old Females
ClinicalTrials.gov ID: NCT00365378
Acronym / sponsor ID: V501-005
Conditions: HPV 16 Infection
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 2,409 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Sep 1999
Primary completion: Mar 2004 (actual)
Study completion: Jul 2009 (actual)
First posted: 17 Aug 2006 (estimated)
Results: Posted 9 Apr 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Subjects received HPV 16 L1 VLP vaccine or placebo (1:1 ratio). Endpoints included efficacy, immunogenicity, and safety.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Biological: Comparator: HPV 16 L1 VaccineHPV 16 L1 VLP vaccine
2	Placebo comparator	Biological: Comparator: PlaceboPlacebo

Who may qualify

Ages: 16 to 23 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

Healthy, unmarried females age 16 to 23 years with intact uteri
Not pregnant at enrollment
Agreed to use effective contraception through Month 7 of the study
A lifetime history of 0 to 5 male partners with whom the subjects engaged in at least one episode of insertive intercourse

Key exclusion criteria (3 listed)

No prior history of Human Papillomavirus (HPV) vaccination
No receipt of any other vaccination within 1 month prior to enrollment or plans to receive any other vaccination within 1 month prior to or after any dose of study vaccine
No prior history of an abnormal Papanicolaou (Pap) test showing Squamous intraepithelial lesion (SIL) or biopsy showing Cervical intraepithelial neoplasia (CIN)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Comparator: HPV 16 L1 VaccineAlso: V501A 0.5 intramuscular injection given at Day 1, Month 2, and Month 6	Biological	1
Comparator: PlaceboA 0.5 intramuscular placebo injection given at Day 1, Month 2, and Month 6	Biological	2

Primary outcome

Incidence of Persistent HPV 16 Infection
Time frame: Through Month 48
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.
Incidence of HPV 16-related CIN1, CIN2 or C1N3
Time frame: Through Month 48
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.
Serum Anti-HPV 16 Geometric Mean Titers
Time frame: Month 7
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".

Results and safety

Results posted to the registry on 9 Apr 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
HPV 16 L1 VLP (Group 1)	1,204	993
Placebo (Group 2)	1,205	1,038
Extension	0	0

Primary outcome: Incidence of Persistent HPV 16 Infection

Time frame: Through Month 48. Number. Unit: Incidence per 100 person-years

Measure	HPV 16 L1 VLP (Group 1) n = 755	Placebo (Group 2) n = 750
Value	0.3	4.9

HPV 16 L1 VLP (Group 1) vs Placebo (Group 2): Vaccine Efficacy: 94.3 (95% CI 87.8 to 97.7)

Population analysed: 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

Primary outcome: Incidence of HPV 16-related CIN1, CIN2 or C1N3

Time frame: Through Month 48. Number. Unit: Incidence per 100 person-years

Measure	HPV 16 L1 VLP (Group 1) n = 755	Placebo (Group 2) n = 750
Value	0.0	1.0

HPV 16 L1 VLP (Group 1) vs Placebo (Group 2): Vaccine Efficacy: 100.0 (95% CI 84.0 to 100.0)

Population analysed: 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

Primary outcome: Serum Anti-HPV 16 Geometric Mean Titers

Time frame: Month 7. Geometric mean (95% Confidence Interval). Unit: milliMerck units/ml (mMU/ml)

Measure	HPV 16 L1 VLP (Group 1) n = 684	Placebo (Group 2) n = 680
Value	1518.8 (1385.5 to 1665.0)	6.0 (6.0 to 6.0)

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HPV 16 L1 VLP (Group 1)	19 of 1,191 (1.6%)	1,025 of 1,191 (86.1%)	Not reported
Placebo (Group 2)	20 of 1,196 (1.7%)	1,013 of 1,196 (84.7%)	Not reported
Extension	1 of 400 (0.3%)	0 of 0	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16394035Mao 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.
Background: PubMed 12444178Koutsky 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.
Background: PubMed 18435868Paavonen 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.
Background: PubMed 18313445Barr 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.
Background: PubMed 17544766Ault 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.
Background: PubMed 17445955Fraser 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.
Derived from this study: PubMed 41276263Bergman 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.
Derived from this study: PubMed 22277329Wiley 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.

Related trials for HPV 16 Infection

RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer
Active, not recruitingPhase 4
An Exploratory Open-Label Clinical Trial Evaluating the Immunogenicity of the 9-valent 2-dose HPV Vaccination Regimen
HPV Infection
Active, not recruitingPhase 3
Efficacy Against Oral Persistent Infection, Immunogenicity and Safety of the 9-valent Human Papillomavirus Vaccine (9vHPV) in Men Aged 20-45 Years (V503-049)
Papillomavirus Infections
Recruiting
Multicenter Prospective Non-randomized Controlled Study of ALA-PDT for LSIL With HPV16/18 Infection
HPV-16/18, Photodynamic Therapy (PDT)
Not yet recruiting
Epidemiology of Anal Human Papillomavirus Carriage in Female Solid Organ Transplant Recipients With More Than 10 Years of Immunosuppression
Human Papillomavirus Infection, Anal HPV Infection

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Comparator: HPV 16 L1 Vaccine in people with HPV 16 Infection, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Apr 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Persistent HPV 16 Infection (time frame: Through Month 48). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00365378, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2015.