Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ongoing, recruiting
Participants planned
498
Countries
1
Sites
41
Vulvar High-Grade Squamous Intraepithelial Lesion (vHSIL)
To evaluate the efficacy of adjuvant nonavalent HPV vaccination in women who will undergo treatment for (pathology proven) vulvar HSIL in preventing clinical recurrence HSIL up to 24 months.
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Female
- Therapeutic area
- Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Virus Diseases [C02]
- Trial duration
- 4 Mar 2024 → ongoing
- Decision date (initial)
- 2024-01-24
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- KWF (Dutch Cancer Society)
External identifiers
- EU CT number
- 2023-506792-94-00
- ClinicalTrials.gov
- NCT06052696
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Prophylaxis
To evaluate the efficacy of adjuvant nonavalent HPV vaccination in women who will undergo treatment for (pathology proven) vulvar HSIL in preventing clinical recurrence HSIL up to 24 months.
Secondary objectives 10
- The effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months.
- Complete remission after treatment in vaccination versus placebo at 6 and 12 months in primary episode vHSIL versus recurrence.
- The effectiveness of adjuvant vaccination in different treatments of vHSIL (laser, imiquimod, excision) after 24 months.
- Additional treatment for vHSIL needed in the study period, and differences between the study groups.
- The effect of vaccination versus placebo on different HPV types (HPV type of primary and recurrence).
- The difference in immune response in HPV vaccination versus placebo vaccination.
- Cost effectiveness (IMTA Medical Consumption Questionnaire (iMCQ) and IMTA Productivity Cost Questionnaire (iPCQ) will be used).
- Quality of life (measured by Euroqol 5D-5L questionnaire) and sexual health (measured by Female Sexual Function Index, FSFI questionnaire) improved after vaccination compared to placebo?
- The effect of vaccination versus placebo on CIN/cervical cytology of the uterine Cervix.
- Long-term follow-up: The difference between vaccination and placebo group in number of recurrences of vHSIL (5 and 10 years) and the occurrence of vulvar malignancies (2, 5 and 10 years).
Conditions and MedDRA coding
Vulvar High-Grade Squamous Intraepithelial Lesion (vHSIL)
Regulatory references
| EU CT number | Title | Sponsor |
|---|---|---|
| 2018-002764-94 | Adjuvant vaccination against HPV in surgical treatment of CIN lesions, a Randomised Controlled Trial, Vaccinatie tegen HPV bij behandeling van CIN afwijkingen. Een RCT. (VACCIN studie) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Women 18 years or older
- Vulvar High-grade Squamous Intraepithelial Lesion (HSIL), histologically proven
- Planned for treatment (surgical, laser or imiquimod) for vulvar High Grade Squamous Intraepithelial Lesion
Exclusion criteria 6
- Prior HPV vaccination
- (Micro-) invasive carcinoma or history of HPV related genital carcinoma (cervix, anal, vulva)
- Pregnancy
- Women allergic to vaccine components
- HIV infection
- Immune compromised patients (currently on immunosuppressive medication)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo up to 24 months post-treatment.
Secondary endpoints 10
- Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months.
- Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months for primary vHSIL versus recurrent vHSIL.
- Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between the different treatment modalities.
- Difference in number and percentage for additional treatment necessary after primary treatment.
- Description and percentage of different HPV types. Percentage clearance of primary HPV type for vaccination versus placebo.
- Number of HPV antibodies and percentage of increase or decrease after vaccination. Is there correlation between number or percentage of recurrence. Is that different in primary versus recurrent episode vHSIL.
- Incremental cost-effectiveness ratio (ICER), described the difference in costs and budget impact analysis.
- Description and change in numeric value and percentage in different score form questionnaires. Percentage increase of decrease quality of life, sexual impact and productivity impact.
- Difference number and percentage in HPV types cervical cytology and vHSIL before and after vaccination.
- Difference in number and percentage in recurrence rate of vulvar HSIL and vulvar cancer between HPV vaccination and placebo. Other HPV related disease known?
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Gardasil 9 suspension for injection. Human Papillomavirus 9-valent Vaccine (Recombinant, adsorbed)
PRD4575515 · 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 INJECTION
- Max daily dose
- 1 ml millilitre(s)
- Max total dose
- 3 ml millilitre(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- J07BM03 — -
- Marketing authorisation
- EU/1/15/1007/001
- MA holder
- MERCK SHARP & DOHME BV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- R.L.O van de Laar
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- R.L.O van de Laar
Locations
1 EU/EEA country · 41 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 498 | 41 |
| Rest of world | — | 0 | — |
Investigational sites
Frisius MC
Gynaecology, Henri Dunantweg 2, 8934 AD, Leeuwarden
Haga Hospital
Gynaecology, Els Borst-Eilersplein 275, 2545 AA, 's-Gravenhage
Noordwest Ziekenhuisgroep Stichting
Gynaecology, Wilhelminalaan 12, 1815 JD, Alkmaar
Onze Lieve Vrouwen Gasthuis
Gynaecology, PO box 95500, Netherlands, Amsterdam
ETZ Elisabeth
Gynaecology, Hilvarenbeekseweg 60, Noord-Brabant, Tilburg
St.Anna
Gynaecology, Bogardeind 2, 5664 EH, Gelderop
Zaans Medisch Centrum Stichting
Gynaecology, Koningin Julianaplein 58, 1502 DV, Zaandam
Canisius Wilhelmina Ziekenhuis
Gynaecology, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen
Rijnstate Ziekenhuis Stichting
Gynaecology, Wagnerlaan 55, 6815 AD, Arnhem
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Gynaecologic oncology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Catharina Ziekenhuis Stichting
Gynaecology, Michelangelolaan 2, 5623 EJ, Eindhoven
Stichting Martini Ziekenhuis
Gynaecology, Van Swietenplein 1, 9728 NT, Groningen
St. Antonius Ziekenhuis
Gynaecology, Soestwetering 1, 3543 AZ, Utrecht
Medisch Spectrum Twente
Obstetrics & Gynaeccology, Koningsplein 1, 7512 KZ, Enschede
Maxima Medisch Centrum
Obstetrics & Gynaeccology, De Run 4600, 5504 DB, Veldhoven
Leids Universitair Medisch Centrum (LUMC)
Gynaecologic oncology, Albinusdreef 2, 2333 ZA, Leiden
IJsselland Ziekenhuis
Obstetrics & Gynaecology, Prins Constantijnweg 2, 2906 ZC, Capelle Aan Den Ijssel
Isala Klinieken Stichting
Obstetrics & Gynecology, Dokter Van Heesweg 2, 8025 AB, Zwolle
Reinier de Graaf Groep
Gynaecology, Reinier De Graafweg 5, 2625 AD, Delft
Sint Franciscus Vlietland Groep Stichting
Gynaecology, Kleiweg 500, 3045 PM, Rotterdam
Universitair Medisch Centrum Utrecht
Gynaecologic oncology, Heidelberglaan 100, 3584 CX, Utrecht
Flevoziekenhuis Stichting
Gynaecologic oncology, Hospitaalweg 1, 1315 RA, Almere
University Hospital Maastricht
Gynaecology, P. O. Box 616, 6200 MD, Maastricht
Universitair Medisch Centrum Groningen
Gynaecologic oncology, Hanzeplein 1, 9713 GZ, Groningen
Amphia Hospital
Gynaecology, Molengracht 21, 4818 CK, Breda
Maasstad Ziekenhuis Stichting
Obstetrics & Gynaeccology, Maasstadweg 21, 3079 DZ, Rotterdam
Diakonessenhuis Stichting
Obstetrics & Gynaecology, Bosboomstraat 1, 3582 KE, Utrecht
Amsterdam UMC
Gynaecologic oncology, De Boelelaan 1117, 1081 HV, Amsterdam
Roosevelt kliniek
Gynaecology, Rooseveltstraat 82A, 2321 BM, Leiden
Gelre Hospitals
Gynaecology, Albert Schweitzerlaan 31, 7334 DZ, Apeldoorn
Ikazia Ziekenhuis
Gynaecology, Montessoriweg 1, 3083 AN, Rotterdam
Deventer Ziekenhuis
Gynaecology, Nico Bolkesteinlaan 75, 7416 SE, Deventer
Zuyderland Medisch Centrum Stichting
Gynaecology, Henri Dunantstraat 5, 6419 PC, Heerlen
Dijklander Ziekenhuis
Gynaecology, Maelsonstraat 3, 1624 NP, Hoorn Nh
Stichting Radboud University Medical Center
Gynaecology, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Jeroen Bosch Ziekenhuis Stichting
Gynaecology oncology, Henri Dunantstraat 1, 5223 GZ, 'S-Hertogenbosch
Spaarne Gasthuis
Gynaecology, Boerhaavelaan 22, 2035 RC, Haarlem
Ziekenhuis St Jansdal
Obstetrics & Gynaecology, Wethouder Jansenlaan 90, 3844 DG, Harderwijk
Albert Schweitzer Ziekenhuis
Gynaecology, Albert Schweitzerplaats 25, 3318 AT, Dordrecht
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Gynaecologic oncology, Plesmanlaan 121, 1066 CX, Amsterdam
Bravis Ziekenhuis
Gynaecology, Boerhaaveplein 1, 4624 VT, Bergen Op Zoom
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-03-04 | 2024-03-05 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 3 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | K1 Recruitment procedure NL | 1 |
| Recruitment arrangements (for publication) | K2_Other subject information material website Erasmus MC | 1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF desription Vulvaccin | 2 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-10-02 | Netherlands | Acceptable 2024-01-24
|
2024-01-24 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-06-27 | Netherlands | Acceptable | 2024-08-28 |
| 3 | SUBSTANTIAL MODIFICATION | SM-4 | 2026-02-05 | Netherlands | Acceptable | 2026-03-11 |