​​A scientific study on a vaccine against HPV infection (human papilloma virus) ​(a vaccine for the prevention of cervical cancer and genital warts)​

2023-508683-30-00 Protocol V503-021 Therapeutic confirmatory (Phase III) Ongoing, recruitment ended

Start 14 Mar 2008 · Status Ongoing, recruitment ended · 3 EU/EEA countries · 7 sites · Protocol V503-021

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruitment ended
Participants planned 2,220
Countries 3
Sites 7

​9vHPV vaccine is indicated in females ≥ 9 years of age in the prevention of cervical, vulvar, vaginal, and anal cancer; precancerous or dysplastic lesions; and persistent infections caused by Human Papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58, and genital warts (condyloma acuminata) caused by HPV types 6 and 11.​

To assess the long-term effectiveness of the 9vHPV vaccine by monitoring the combined incidence of Cervical Intraepithelial Neoplasia (CIN) 2, CIN 3, Adenocarcinoma In Situ (AIS) and cervical cancer related to HPV 16, 18, 31, 33, 45, 52, and 58 in women from Protocol V503-001 in the Nordic region vaccinated with the 9v…

Key facts

Sponsor
Merck Sharp & Dohme LLC
Participant type
Healthy volunteers
Age range
18-64 years
Gender
Female
Therapeutic area
Diseases [C] - Virus Diseases [C02]
Trial duration
14 Mar 2008 → ongoing
Decision date (initial)
2024-12-01
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Merck Sharp & Dohme LLC

External identifiers

EU CT number
2023-508683-30-00
EudraCT number
2013-003549-40
WHO UTN
U1111-1305-8498

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Others, Safety, Efficacy

To assess the long-term effectiveness of the 9vHPV vaccine by monitoring the combined incidence of Cervical Intraepithelial Neoplasia (CIN) 2, CIN 3, Adenocarcinoma In Situ (AIS) and cervical cancer related to HPV 16, 18, 31, 33, 45, 52, and 58 in women from Protocol V503-001 in the Nordic region vaccinated with the 9vHPV vaccine

Secondary objectives 3

  1. To estimate the combined incidence of CIN 2, CIN 3, AIS, and cervical cancer related to non-vaccine HPV types 35, 39, 51, 56 and 59 in women from Protocol V503-001 in the Nordic region vaccinated with the 9vHPV vaccine
  2. To estimate long-term effectiveness of the 9vHPV vaccine against CIN 1, CIN 2, and CIN 3, AIS, cervical cancer, vulvar cancer (in situ or invasive), or vaginal cancer (in situ or invasive) related to HPV 6, 11,16, 18, 31, 33, 45, 52, and/or 58
  3. To evaluate the long-term HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibody responses generated by the 9vHPV vaccine

Conditions and MedDRA coding

​9vHPV vaccine is indicated in females ≥ 9 years of age in the prevention of cervical, vulvar, vaginal, and anal cancer; precancerous or dysplastic lesions; and persistent infections caused by Human Papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58, and genital warts (condyloma acuminata) caused by HPV types 6 and 11.​

VersionLevelCodeTermSystem organ class
21.1 LLT 10071147 Human papilloma virus immunization 10042613

Regulatory references

Plan to share IPD
Yes
EU CT numberTitleSponsor
2007-003528-39 A Randomized, International, Double-Blinded (With In-House Blinding), Controlled With GARDASIL™, Dose-Ranging, Tolerability, Immunogenicity, and Efficacy Study of a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine Administered to 16- to 26-Year-Old Women

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

  1. Randomized into the V503-001 (NCT00543543) study from a Denmark, Norway, or Sweden site and participated in the study by receiving either the selected dose formulation of the 9vHPV vaccine or GARDASIL
  2. Agrees to allow passive follow-up, analysis of biopsy specimens, future contact from the National Registry Study Centers, and serum collection

Exclusion criteria 1

  1. There are no exclusion criteria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Combined Incidence of Human Papillomavirus (HPV) Type 16, 18, 31, 33, 45, 52, or 58-related CIN Grades 2 or 3, Adenocarcinoma in Situ (AIS), and Cervical Cancer in Cohort 1

Secondary endpoints 4

  1. Combined Incidence of CIN 2, CIN 3, AIS, or cervical cancer related to HPV 35, 39, 51, 56, or 59
  2. Combined Incidence of CIN (any grade), AIS, cervical cancer, vulvar cancer, or vaginal cancer related to HPV 6, 11, 16, 18, 31, 33, 45, 52, or 58
  3. Geometric Mean Titers (GMTs) of HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58
  4. Seropositivity rates of HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Gardasil 9 suspension for injection in a pre-filled syringe. Human Papillomavirus 9-valent Vaccine (Recombinant, adsorbed)

PRD7273288 · Product

Active substance
Human Papillomavirus Type 31 L1 Protein - Adsorbed - in the Form of Virus-Like Particles Produced in Yeast Cells (Saccharomyces Cerevisiae Canade 3C-5 (Strain 1895)) by Rdna
Pharmaceutical form
SUSPENSION FOR INJECTION
Route of administration
INTRAMUSCULAR
Max daily dose
0 ml millilitre(s)
Max total dose
0 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
J07BM03 — -
Marketing authorisation
EU/1/15/1007/004
MA holder
MERCK SHARP & DOHME B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation
Merck Sharp & Dohme LLC
Address
126 East Lincoln Avenue
City
Rahway
Postcode
07065-4607
Country
United States

Scientific contact point

Organisation
Merck Sharp & Dohme LLC
Contact name
Alain Luxembourg

Public contact point

Organisation
Merck Sharp & Dohme LLC
Contact name
Alain Luxembourg

Third parties 1

OrganisationCity, countryDuties
Q Squared Solutions Holdings LLC
ORG-100043288
Valencia, United States Other

Locations

3 EU/EEA countries · 7 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Authorised, recruitment pending 1,844 5
Norway Ongoing, recruiting 318 1
Sweden Ended 58 1
Rest of world 0

Investigational sites

Denmark

5 sites · Authorised, recruitment pending
Sanos A/S
Sanos Clinic Vejle, Boulevarden 19g, 7100, Vejle
Sanos A/S
Sanos Clinic Gandrup, Borgergade 39, 9362, Gandrup
Sanos A/S
Sanos Clinic Herlev, Herlev Hovedgade 82, 2730, Herlev
Danish Cancer Society Research Center
Unit of Virus, Lifestyle, and Genes, Strandboulevarden 49, 2100, Copenhagen Oe
Odense University Hospital
Department of Gynecology and Obstetrics, Kloevervaenget 47, 5000, Odense C

Norway

1 site · Ongoing, recruiting
Cancer Registry Of Norway
Cancer Registry of Norway, Ullernchausseen 64, 0379, Oslo

Sweden

1 site · Ended
Karolinska University Hospital
Insitutionen för laboratoriemedicin, Forskningsgatan F56, Halsovagen, Flemingsberg, Huddinge

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Norway 2008-03-14 2008-03-14
Sweden 2016-02-08 2025-07-30 2024-05-28 2024-05-29

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2023-508683-30_for pub 03
Recruitment arrangements (for publication) K1_Recruitment Arrangements and IC Procedure LT FU_NOR_EN_SM04_for pub 1-0
Recruitment arrangements (for publication) K1_Recruitment Arrangements_DNK_EN_for pub 1-0
Recruitment arrangements (for publication) K2_Recruitment Doc Letter odaf Invitation_Histo reminder_DNK_DA_for pub 1-0
Recruitment arrangements (for publication) K2_Recruitment Doc Letter of Invitation_DNK_DA_for pub 1-0
Recruitment arrangements (for publication) K2_Recruitment Doc Letter of Invitation_FU_DNK_DA_for pub 1-0
Recruitment arrangements (for publication) K2_Recruitment Doc Letter of Invitation_Histo_DNK_DA_for pub 1-0
Recruitment arrangements (for publication) K2_Recruitment Doc Letter of Invitation_reminder_DNK_DA_for pub 1-0
Recruitment arrangements (for publication) K2_Recruitment Doc Subject Recruitment_DNK_DA_for pub 02Sep2024
Recruitment arrangements (for publication) V503-021 CTIS Placeholder document 1
Subject information and informed consent form (for publication) L1_ICF_Main addendum_NOR_NN_SM04-RFI005_for pub 16DEC2025
Subject information and informed consent form (for publication) L1_ICF_Main adult consent_DNK_DA_for pub 1-0
Subject information and informed consent form (for publication) L1_ICF_Main adult consent_eConsent_DNK_DA_for pub 1-0
Subject information and informed consent form (for publication) L1_ICF_Main consent_DNK_DA_for pub 00R
Subject information and informed consent form (for publication) L1_ICF_Main consent_eConsent_DNK_DA_for pub 00
Subject information and informed consent form (for publication) L1_ICF_Main consent_NOR_NN_for pub 8
Subject information and informed consent form (for publication) L1_ICF_Main consent_SWE_SV_for pub 07AUG2013
Subject information and informed consent form (for publication) L1_ICF_Main GDPR addendum_NOR_NN_SM04-RFI002_for pub 23MAY2022
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Gardasil9_for pub 25JUL2023
Synopsis of the protocol (for publication) D1_PPLS_2023-508683-30_for pub 1-0
Synopsis of the protocol (for publication) D1_PPLS_2023-508683-30_SWE_SV_for pub 1-0

Application history

5 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-04-17 Norway Acceptable
2024-05-24
2024-05-24
2 SUBSTANTIAL MODIFICATION SM-1 2024-07-03 Norway Acceptable
2024-09-02
2024-09-02
3 SUBSEQUENT ADDITION OF MSC APP-3 2024-09-09 Acceptable
2024-09-02
2024-12-01
4 SUBSTANTIAL MODIFICATION SM-4 2025-09-17 Norway Acceptable
2025-11-17
2025-11-17
5 NON SUBSTANTIAL MODIFICATION NSM-1 2025-12-18 Norway Acceptable
2025-11-17
2025-12-18