Cervical CancerPhase 3NCT03158220

Immunogenicity and Tolerability of Broad Spectrum Human Papillomavirus (HPV) Vaccine in Adult and Young Adult Women (V503-004)

A Phase 3 study testing V503 in people with Cervical Cancer and Vulvar Cancer, run by Merck Sharp & Dohme LLC at 24 sites in 6 countries.

Completed

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

Official record

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Trial summary

This study will assess the safety and immunogenicity of GARDASIL®9 (V503) in 16- to 45-year-old women. The primary hypothesis of the study states that anti-HPV 16, 18, 31, 33, 45, 52, and 58 geometric mean titers (GMTs) at 4 weeks postdose 3 are non-inferior in adult women as compared with GMTs in young adult women. Read more about this study

Who is it for?: Ages 16 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for: Cervical Cancer, Vulvar Cancer, Vaginal Cancer
What is being tested?: V503
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,212 participants
Where: 24 sitesin 6 countries
Study dates: 20 Sep 2017to 19 Nov 2018
Phase: Phase 3
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 45 years
Women only
Healthy volunteers accepted
Child, Adult

Who may be able to join

good physical health

Who cannot join

history of an abnormal Pap (Papanicolaou) test or abnormal cervical biopsy results
history of HPV-related condition
history of known prior vaccination with an HPV vaccine
pregnant
user of recreational or illicit drugs
history of severe allergic reaction, including known allergy to any vaccine component

Show all 10Show fewer

immunocompromised
history of certain medications or is currently taking or has taken certain medications (details will be discussed at the time of consent)
has thrombocytopenia or other coagulation disorder
concurrently enrolled in a clinical study of investigational agent

Trial locations and contacts

24 sites in 6 countries.

Country

City, postcode or hospital

24 sites in 6 countries

Finland5 sites

HUS Katiloopiston sairaala ( Site 0009)
Helsinki
Ita-Helsingin Rokotetutkimuskeskus ( Site 0011)
Helsinki
Porin Rokotetutkimusklinikka ( Site 0012)
Pori
Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0010)
Tampere
Turun rokotetutkimusklinikka ( Site 0037)
Turku

Other trials in Finland

Germany5 sites

Universitaetsmedizin Berlin Charite ( Site 0016)
Berlin
Universitaetsklinikum Duesseldorf ( Site 0014)
Düsseldorf
Praxis Dr. Peters ( Site 0015)
Hamburg
Universitaetsklinikum Hamburg-Eppendorf ( Site 0017)
Hamburg
Universitaetsklinikum Tuebingen ( Site 0013)
Tübingen

Other trials in Germany

Spain5 sites

Complejo Hospitalario de Torrecardenas ( Site 0030)
Almería
CAP Centelles ( Site 0027)
Centelles, Barcelona
Institut Catala Oncologia de Bellvitge - ICO ( Site 0026)
L'Hospitalet de Llobregat
Hospital Sanitas La Moraleja ( Site 0031)
Madrid
Hospital Universitario Infanta Leonor ( Site 0028)
Madrid

Other trials in Spain

Belgium4 sites

Universitair Ziekenhuis Antwerpen ( Site 0007)
Edegem
Universitair Ziekenhuis Gent ( Site 0006)
Ghent
Universitair Ziekenhuis Gasthuisberg ( Site 0005)
Leuven
University of Antwerp ( Site 0004)
Wilrijk

Other trials in Belgium

Italy3 sites

Istituto Nazionale dei tumori ( Site 0020)
Milan, Milan
Ospedale San Raffaele ( Site 0022)
Milan
Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello ( Site 0023)
Palermo

Other trials in Italy

Austria2 sites

Universitatsklinik fuer Frauenheilkunde und Geburtshilfe ( Site 0002)
Graz
Klin. Abtlg. fuer Gynaekologie und Geburtshilfe ( Site 0001)
Vienna

Other trials in Austria

About this study

Official title: An Open-Label Phase III Clinical Trial to Study the Immunogenicity and Tolerability of GARDASIL®9 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Adult Women (27- to 45-Year-Olds) Compared to Young Adult Women (16 to 26 Year Olds)

Conditions: Cervical Cancer, Vulvar Cancer, Vaginal Cancer, Genital Warts, Human Papillomavirus Infection
Being tested: V503
Medical subject headings: Uterine Cervical Neoplasms, Vulvar Neoplasms, Vaginal Neoplasms, Condylomata Acuminata, Papillomavirus Infections

What participants receive

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

V503Biological
Also called GARDASIL®9 (HPV 9-valent vaccine [recombinant, adsorbed]); HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6

Study groups in NCT03158220
Study group	Role	What they receive
Adult Women 27- to 45-years Old	Experimental	Adult women 27- to 45-years old will receive V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6. Receives: Biological: V503
Young Adult Women 16- to 26-years Old	Active comparator	Young adult women 16- to 26-years old will receive V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6. Receives: Biological: V503

What is being measured

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

Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type
Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). Statistical comparisons between arms was performed for the HPV types considered oncogenic (HPV Types 16/18/31/33/45/52/58).
Measured: 4 weeks post vaccination 3 (Month 7)

Secondary outcomes (6)

Percentage of Participants That Experienced at Least 1 Adverse Event (AE)
An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs was assessed.
Measured: Up to 1 month post vaccination 3 (up to 7 months)
Percentage of Participants Who Had Study Vaccine Discontinued Due to Adverse Event.
An adverse event is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study vaccine due to an adverse event regardless of study completion status was assessed.
Measured: Up to 1 month post vaccination 3 (up to 7 months)
Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event
Participants were asked to record any injection-site reactions prompted in the Vaccination Report Card, i.e., injection-site tenderness, swelling, or redness, occurring after each study vaccination (solicited injection-site reactions). The percentage of participants with 1 or more solicited injection-site AE was assessed.
Measured: Up to 5 days post any vaccination
Percentage of Participants That Reported at Least 1 Systemic Adverse Event
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs. The percentage of participants that reported at least 1 systemic AE was assessed
Measured: Up to 15 days post any vaccination
Percentage of Participants With Elevated Temperature (Fever)
Participants were asked to record oral body temperature in the Vaccination Report Card. The percentage of participants with elevated temperature (≥37.8°C or 100.0°F) was assessed.
Measured: Up to 5 days post any vaccination
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types
Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. The percentage of participants who were seronegative on Day 1 and have anti-HPV titer greater or equal to the type-specific serostatus cutoff at 4 weeks postdose 3 was assessed.
Measured: 4 weeks post vaccination 3 (Month 7)

Timeline

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

20 Sep 201719 Nov 2018

First posted18 May 2017
Study start20 Sep 2017
Primary completion19 Nov 2018
Study completion19 Nov 2018

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 (1)Papers the sponsor has linked to this study.
Other trials for Cervical CancerStudies 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 3
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 1,212 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03158220
Sponsor's protocol ID: V503-004
Status last verified: Nov 2019
First submitted: 16 May 2017
Last updated: 21 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Joura EA, Ulied A, Vandermeulen C, Rua Figueroa M, Seppa I, Hernandez Aguado JJ, Ahonen A, Reich O, Virta M, Perino A, Peris Tuser M, Peters K, Origoni M, Raspagliesi F, Tjalma WAA, Tummers P, Woelber L, Nieminen P, van Damme P, Sehouli J, Fiol Ruiz G, Brucker S, Fehm T, Cheon K, Rawat S, Luxembourg A, Wittke F. Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27-45 years of age compared to women 16-26 years of age: An open-label phase 3 study. Vaccine. 2021 May 12;39(20):2800-2809. doi: 10.1016/j.vaccine.2021.01.074. Epub 2021 Mar 3.
PubMed 33676783

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?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 21 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Phase III Clinical Trial to Study the Immunogenicity and Tolerability of GARDASIL®9 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Adult Women (27- to 45-Year-Olds) Compared to Young Adult Women (16 to 26 Year Olds)
ClinicalTrials.gov ID: NCT03158220
Acronym / sponsor ID: V503-004
Conditions: Cervical Cancer, Vulvar Cancer, Vaginal Cancer, Genital Warts, Human Papillomavirus Infection
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,212 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 20 Sep 2017 (actual)
Primary completion: 19 Nov 2018 (actual)
Study completion: 19 Nov 2018 (actual)
First posted: 18 May 2017 (actual)
Results: Posted 21 Nov 2019

Clinical summary

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

Study design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Adult Women 27- to 45-years Old	Experimental	Biological: V503Adult women 27- to 45-years old will receive V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Young Adult Women 16- to 26-years Old	Active comparator	Biological: V503Young adult women 16- to 26-years old will receive V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.

Who may qualify

Ages: 16 to 45 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (1 listed)

good physical health

Key exclusion criteria (10 listed)

history of an abnormal Pap (Papanicolaou) test or abnormal cervical biopsy results
history of HPV-related condition
history of known prior vaccination with an HPV vaccine
pregnant
user of recreational or illicit drugs

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
V503Also: GARDASIL®9 (HPV 9-valent vaccine [recombinant, adsorbed]); HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6	Biological	Adult Women 27- to 45-years Old, Young Adult Women 16- to 26-years Old

Primary outcome

Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type
Time frame: 4 weeks post vaccination 3 (Month 7)
Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). Statistical comparisons between arms was performed for the HPV types considered oncogenic (HPV Types 16/18/31/33/45/52/58).

6 secondary outcomes

Percentage of Participants That Experienced at Least 1 Adverse Event (AE)
Time frame: Up to 1 month post vaccination 3 (up to 7 months)
Percentage of Participants Who Had Study Vaccine Discontinued Due to Adverse Event.
Time frame: Up to 1 month post vaccination 3 (up to 7 months)
Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event
Time frame: Up to 5 days post any vaccination
Percentage of Participants That Reported at Least 1 Systemic Adverse Event
Time frame: Up to 15 days post any vaccination
Percentage of Participants With Elevated Temperature (Fever)
Time frame: Up to 5 days post any vaccination
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types
Time frame: 4 weeks post vaccination 3 (Month 7)

Results and safety

Results posted to the registry on 21 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Women 16-26 Years of Age	570	553
Women 27-45 Years of Age	642	626

Primary outcome: Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type

Time frame: 4 weeks post vaccination 3 (Month 7). Geometric mean (95% Confidence Interval). Unit: mMU/mL

Measure	Women 16-26 Years of Age n = 485	Women 27-45 Years of Age n = 533
Anti-HPV 6	787.8 (732.5 to 847.2)	638.4 (594.9 to 685.0)
Anti-HPV 11	598.7 (558.7 to 641.6)	453.5 (424.1 to 485.0)
Anti-HPV 16	3075.8 (2863.4 to 3303.9)	2147.5 (2001.1 to 2304.5)
Anti-HPV 18	744.5 (685.0 to 809.1)	532.1 (491.8 to 575.7)
Anti-HPV 31	596.1 (551.1 to 644.9)	395.7 (367.0 to 426.6)
Anti-HPV 33	354.5 (331.7 to 378.9)	259.0 (242.9 to 276.1)
Anti-HPV 45	214.9 (197.7 to 233.7)	145.6 (134.4 to 157.7)
Anti-HPV 52	346.5 (324.0 to 370.5)	244.7 (229.4 to 261.0)

Women 16-26 Years of Age vs Women 27-45 Years of Age: Fold Difference: 0.70 (95% CI 0.63 to 0.77), p < 0.001, ANOVA
Women 16-26 Years of Age vs Women 27-45 Years of Age: Fold Difference: 0.71 (95% CI 0.64 to 0.80), p < 0.001, ANOVA
Women 16-26 Years of Age vs Women 27-45 Years of Age: Fold Difference: 0.66 (95% CI 0.60 to 0.74), p < 0.001, ANOVA

Population analysed: Received all 3 vaccinations of the correct dose and within acceptable day ranges, had evaluable serology results at Day 1 and Month 7, must have been seronegative to the appropriate HPV type at Day 1 and had no protocol deviations that could interfere with the evaluation of participant's immune response to the 9vHPV vaccine.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 1 month post vaccination 3 (up to 7 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Women 16-26 Years of Age	6 of 570 (1.1%)	518 of 570 (90.9%)	0 of 570
Women 27-45 Years of Age	8 of 640 (1.3%)	574 of 640 (89.7%)	0 of 640

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33676783Joura EA, Ulied A, Vandermeulen C, Rua Figueroa M, Seppa I, Hernandez Aguado JJ, Ahonen A, Reich O, Virta M, Perino A, Peris Tuser M, Peters K, Origoni M, Raspagliesi F, Tjalma WAA, Tummers P, Woelber L, Nieminen P, van Damme P, Sehouli J, Fiol Ruiz G, Brucker S, Fehm T, Cheon K, Rawat S, Luxembourg A, Wittke F. Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27-45 years of age compared to women 16-26 years of age: An open-label phase 3 study. Vaccine. 2021 May 12;39(20):2800-2809. doi: 10.1016/j.vaccine.2021.01.074. Epub 2021 Mar 3.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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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 Director study director

Merck Sharp & Dohme LLC

24 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing V503 in people with Cervical Cancer and Vulvar Cancer, run by Merck Sharp & Dohme LLC at 24 sites in 6 countries.

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 1 inclusion and 10 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 21 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Finland, Germany, Spain, Belgium, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 21 Nov 2019). 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?

Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type (time frame: 4 weeks post vaccination 3 (Month 7)). 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 NCT03158220, which also lists 1 linked publication.

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 21 Nov 2019.