Multicenter, randomized, double-blinded, placebo-controlled phase 3 trial to evaluate nonavalent HPV vaccine as a secondary prevention in patients treated for human papilloma virus related high-grade squamous intraepithelial lesions.(BioHPV)

2024-520140-42-00 Protocol 2024/4031 Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 16 sites · Protocol 2024/4031

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 984
Countries 1
Sites 16

Patients with primary HPV high-grade squamous intra-epithelial lesions (HSIL) at any site (vulvar VIN, vaginal VaIN, penile (PeIN), cervical CIN, anal AIN) at the time of treatment.

To assess the efficacy of Human papilloma virus (HPV) vaccination as secondary prevention in patients with gynecological or anal HSIL.

Key facts

Sponsor
Institut Gustave Roussy
Participant type
Patients
Age range
18-64 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Decision date (initial)
2026-01-28
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
PHRC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of Human papilloma virus (HPV) vaccination as secondary prevention in patients with gynecological or anal HSIL.

Secondary objectives 6

  1. Further characterization of efficacy: HPV clearance
  2. Further characterization of efficacy: HSIL occurrence at different sites,
  3. Further characterization of efficacy: Occurrence of invasive HPV-related cancer
  4. Further characterization of efficacy: Safety based on reported adverse events
  5. Further characterization of efficacy: The cost-utility (cost per QALY) of HPV vaccination compared to no vaccination (economic evaluation) in patients undergoing HSIL treatment in France
  6. Further characterization of efficacy: The budget impact of HPV vaccination in patients undergoing HSIL treatment in France

Conditions and MedDRA coding

Patients with primary HPV high-grade squamous intra-epithelial lesions (HSIL) at any site (vulvar VIN, vaginal VaIN, penile (PeIN), cervical CIN, anal AIN) at the time of treatment.

VersionLevelCodeTermSystem organ class
21.0 LLT 10064455 HSIL 10038604

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 RANDOMIZATION OF PATIENTS
BioHPV is a randomized, double-blinded, placebo-controlled, multi-center, phase III trial evaluating nonavalent HPV vaccine in patients undergoing HSIL treatment at any site (vulvar, vaginal, cervical, anal, penile). Patients will be randomized in a 1:1 ratio to the control or the active group using stratified randomization. The factors used for randomization will be lesion location (i.e. cervical vs other, HIV status (i.e. HIV+, HIV-), and age (≤45 and >45 years).
 Randomised Controlled Double [{"id":162458,"code":1,"name":"Subject"},{"id":162459,"code":2,"name":"Investigator"}] Gardasil 9™ Group: Vaccination with Gardasil 9'M/Placebo starts prior HSIL treatment (i.e. first dose will be administered maximum 3 months, minimum 2 weeks before HSIL treatment). The second dose is recommended 1-2 months after the first dose, and the third dose will be administered 3-4 months after the second dose.

Follow-up starts after successful HSIL treatment, every 6 months for 2 years
Control Group: Three doses of placebo will be administered intramuscularly according to the shema of nonavalent HPV vaccination.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

  1. Women, men, transgender,18 ≤age ≤55
  2. ECOG performance status ≤ 1
  3. Patients infected with HIV are eligible for the study provided they are receiving antiretroviral therapy with undetectable viral load
  4. Biopsy-proven HPV related HSIL at any site (vulvar VIN, vaginal VaIN, cervical CIN, anal AIN, penile) at baseline
  5. Women of childbearing potential must have a negative urine pregnancy test 24 hours prior to the administration of the first vaccine injection
  6. Sexually active patients must agree to use acceptable and appropriate contraception while included in BIO-HPV study and until the last dose of vaccine
  7. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol
  8. Patients must be affiliated to a social security system or beneficiary of the same
  9. Life expectancy of greater than 5 years

Exclusion criteria 11

  1. History of HPV related cancer (i.e. anal, genital, head and neck)
  2. History of prior treatment of HSIL at the same site then currently treated
  3. Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
  4. Prior HPV vaccination
  5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 21 days prior to the first dose of trial treatment
  6. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment
  7. Prior malignancy active within the previous 3 years except from cancers with an expected PFS at 5 years of >95%
  8. Hypersensitivity to the active substances or to any of the excipients (Listed in the SmPC)
  9. Acute or severe febrile illness. Vaccination must be postponed until the individual has fully recovered
  10. Pregnant women or intent to become pregnant
  11. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The endpoint will be the time to HPV type-specific recurrence of HSIL at the initial site after completed HSIL treatment. Centralised HPV genotyping of the initial HSIL and recurrent lesion will be performed.

Secondary endpoints 9

  1. Time to HPV clearance
  2. Time to HSIL occurrence at different sites
  3. Time to occurrence of invasive HPV-related cancer
  4. Safety based on reported adverse events
  5. Decrease of 50% recurrence rate of HSIL within 2 years of follow-up once the HSIL treatment is completed.
  6. Adverse events (AE) according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCICTCAE)
  7. Viral and Immune signature for HSIL stratification
  8. Assessment of the sexual health of the enrolled patients and current sexual partner(s) at different time points (i.e. baseline, end of 2-years follow-up, end of 5-years follow-up).
  9. Resource use and costs will be assessed from linkage to French National Health Data System (SNDS, Système National des Données de Santé)

Investigational products

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

Test 4

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

PRD4575517 · 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
0.5 ml millilitre(s)
Max total dose
1.5 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
J07BM03 — -
Marketing authorisation
EU/1/15/1007/003
MA holder
MERCK SHARP & DOHME B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

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

PRD4575516 · 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
0.5 ml millilitre(s)
Max total dose
1.5 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
J07BM03 — -
Marketing authorisation
EU/1/15/1007/002
MA holder
MERCK SHARP & DOHME B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

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
0.5 ml millilitre(s)
Max total dose
1.5 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

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
Max daily dose
0.5 ml millilitre(s)
Max total dose
1.5 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
J07BM03 — -
Marketing authorisation
EU/1/15/1007/001
MA holder
MERCK SHARP & DOHME B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo formulation of Gardasil

PRD12038760 · Product

Active substance
Water for Injection
Pharmaceutical form
INJECTION
Route of administration
INTRAMUSCULAR
Max daily dose
0.5 ml millilitre(s)
Max total dose
1.5 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Not Authorised
MA holder
GUSTAVE ROUSSY
Paediatric formulation
No
Orphan designation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Gustave Roussy

48 Total trials 31 Recruiting 13 Ended
Academic / Non-commercial
Sponsor organisation
Institut Gustave Roussy
Address
114 Rue Edouard Vaillant
City
Villejuif
Postcode
94800
Country
France

Scientific contact point

Organisation
Institut Gustave Roussy
Contact name
Bureau projet Promotion- DRC -Regulatory Affairs Officer

Public contact point

Organisation
Institut Gustave Roussy
Contact name
Bureau projet Promotion- DRC -Regulatory Affairs Officer

Locations

1 EU/EEA country · 16 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 984 16
Rest of world — 0 —

Investigational sites

France

16 sites · Authorised, recruitment pending
Centre Hospitalier Universitaire De Montpellier
Obstetrics and Gynecology, 371 Avenue Du Doyen Gaston Giraud, 34091, Montpellier Cedex 5
Assistance Publique Hopitaux De Paris
Proctology, 46 Rue Henri Huchard, 75877, Paris Cedex 18
Institut De Cancerologie De L Ouest
oncology, Boulevard Jacques Monod, 44805, Saint-Herblain Cedex
Hopital Cochin - Port Royal
oncology, 123 bd de Port Royal, 75014, PARIS
Centr Georges Francois Leclerc
Oncology, 1 Rue Professeur Marion, 21000, Dijon
Institut Gustave Roussy
Oncology, 114 Rue Edouard Vaillant, 94800, Villejuif
Hopital Saint Louis
Oncology, 1 Avenue Claude Vellefaux, 75010, Paris
Centre Oscar Lambret
Oncology, 3 Rue Frederic Combemale, 59000, Lille
Institut De Cancerologie De L Ouest
Oncology, 15 Rue Andre Boquel, 49100, Angers
Groupe Hospitalier Diaconesses Croix Saint Simon
Proctology, 125 Rue D Avron, 75020, Paris
Hopitaux Universitaires Pitie Salpetriere
Oncology, 47 To 83 Boulevard De L Hopital, 75013, Paris
Centre Leon Berard
Surgery, 28 Rue Laennec, 69008, Lyon
Unite De Recherche Clinique HIA Begin
oncology, 69 Avenue De Paris, 94160, Saint-Mande
Oncopole Claudius Regaud
oncology, 1 Avenue Irene Joliot Curie, 31100, Toulouse
Institut De Cancerologie De Lorraine
Oncology, 6 Avenue De Bourgogne, 54500, Vandouvre Les Nancy
Clinique mutualiste la Sagesse
Oncology, 4 place saint Guénolé, 35043, Rennes

Results and documents

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

Documents 14 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-520140-42-00_biffe 1.1
Protocol (for publication) D4_Patient facing documents_Carte patient 1.0
Protocol (for publication) D4_Patient facing documents_questionnaire EORTC SHQ-C22_FR 1
Protocol (for publication) D4_Patient facing documents_questionnaire EQ-5D-5L_FR 1
Protocol (for publication) D4_Patient facing documents_Questionnaire MLT_V3_FR 1
Protocol (for publication) D4_Patient facing documents_Questionnaire partenaire_FR 1
Protocol (for publication) D4_Patient facing documents_Questionnaire QoL_FR 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Recruitment arrangements (for publication) K2_document additionnel_biffe 1
Subject information and informed consent form (for publication) L1_IFC patient 1.0
Subject information and informed consent form (for publication) L1_SIS AND IFC partenaire 1.0
Subject information and informed consent form (for publication) L1_SIS_patient 1.1
Summary of Product Characteristics (SmPC) (for publication) E1_RCP_Gardasil-9 1
Synopsis of the protocol (for publication) D1_Protocol synopsis FR_2024-520140-42-00 1.1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-09-24 France Acceptable
2026-01-26
 2026-01-28

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