Phase II Study of HPV Therapeutic Vaccine in HPV Infected Women With Normal Cytology or ASCUS/LSIL

HUMAN PAPILLOMA VIRUS Clinical Trial

— RHEIA-VAC  

Official title:

A Double-blind, Randomised, Placebo-controlled, Phase II Study to Evaluate ProCervix Efficacy to Clear HPV 16 and HPV 18 Infection in Women With Normal Cytology or ASCUS/LSIL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01957878
• Other study ID #: PC10VAC02
• Status: Completed
• Phase: Phase 2
• First received: October 4, 2013
• Last updated: December 1, 2016
• Start date: December 2013
• Est. completion date: October 2016

Study information

• Verified date: December 2016
• Source: Genticel
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPFinland: Finnish National Agency for MedicinesFrance: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Paul-Ehrlich-InstitutNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Spain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

Human Papillomavirus (HPV) 16 and HPV 18 (the two virus genotypes targeted by the ProCervix vaccine) are the most common HPV genotypes associated with at least 70% of squamous cell carcinomas and 82% of adenocarcinomas of the cervix The strategy of therapeutic vaccination with ProCervix is to activate and enhance the patient's cellular immune response to HPV . The therapeutic vaccine will be used for women infected by HPV 16, HPV 18, or both. The vaccine targets these HPV infected women with normal or mild cervical cellular dyskaryosis as detectable infections with oncogenic potential.

This will be a double-blind, randomised, placebo-controlled, parallel group study assessing the efficacy of ProCervix or placebo (concomitantly administered with imiquimod cream).

ProCervix will be delivered with a topical agent, imiquimod, applied to the injection sites as a vaccine adjuvant.

The population proposed for this study represents an otherwise healthy female population who are infected with HPV 16 and/or HPV 18. The safety and tolerability of this therapeutic vaccine has been shown in the ongoing Phase I study, and the proposed population may in theory derive benefit from this vaccine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 239
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 50 Years

Eligibility

Inclusion Criteria:

• A subject will be eligible for inclusion in this study if the following criteria apply:

1. Subject is female between the ages of 25 and 50 years (inclusive).

2. Subject is pre-menopausal .

3. Subject must have cervical HPV 16 and/or 18 infection confirmed by RT-PCR

4. Subject has a cervical cytological evaluation with a normal, ASCUS or LSIL result at baseline.

5. Subject has employed highly effective contraception the month prior to the first vaccination and will agree to employ highly effective contraception for at least 12 months after the first vaccination. .

6. Subject is in general good health based on medical history and physical examination.

7. Subject is able to communicate effectively with study personnel and is considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.

8. Subject voluntarily gives written informed consent to participate in the study.

Exclusion Criteria:

1. Subject has a current acute or chronic disease, other than infection with HPV, which would be expected to interfere with the planned evaluations of response

2. Subject has vaginal atrophy with or without topical hormonal therapies or systemic selective estrogen receptor modulators (SERMs).

3. Subject has prior exposure to HPV prophylactic vaccine or subject has participated in the past in another vaccination clinical trial related to infection with HPV

4. Current high grade lesions or history of untreated high grade cervical lesion (either CIN2 or CIN3).

5. Subject has current or a history of cancer of the cervix.

6. Subject has clinically significant (CS) gynaecological abnormalities that could interfere with study evaluation, in the judgment of the Investigator (e.g. prolapse, myoma, fibroid, hysterectomy).

7. Subject has a laboratory abnormality Grade = 2, as defined using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials,

8. Subject has received any live viral vaccine within 3 months or any other non live vaccine within 2 weeks of first study product administration.

9. Subject has primary or secondary systemic immunosuppression

10. Subject has a history of severe allergy (requiring hospital care) or history of severe asthma

11. Subject has a history of malignant cancer, except the following adequately treated cancers: basal cell carcinoma, or dermatological squamous cell carcinoma.

12. Subject was administered with another investigational drug or vaccine within 30 days prior to the screening visit or is participating in any other study.

13. Subject has a known hypersensitivity to imiquimod.

14. Subject has a history of severe reaction to any drug or vaccination.

15. Subject has a medical condition with clinical and/or biological consequences judged by the Investigator incompatible with vaccination(s).

16. Subject has positive results for human immunodeficiency virus (HIV), hepatitis B virus (HBV) surface antigen (HBsAg), or hepatitis C virus (HCV).

17. Subject has a symptomatic vaginal or genital infection

18. Subject has a history of or currently active genital herpes disease.

19. Subject is pregnant or is breastfeeding.

20. Subject has a positive serum human chorionic gonadotrophin (HCG) result at enrolment.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Genital Infection Viral
• HUMAN PAPILLOMA VIRUS
• Infection
• Papilloma
• Virus Diseases

Intervention

Biological:
• ProCervix
ProCervix consists of two recombinant adenylate cyclase (CyaA) proteins, CyaA-HPV 16E7 (C16-1) and CyaA-HPV 18E7 (C18-1) in a 50/50 ratio (C16C18-2 Ag mixture). ProCervix is adjuvanted by Aldara™, a cream containing 5% of imiquimod
• Placebo
Placebo matching ProCervix and adjuvanted by Aldara™, a cream containing 5% of imiquimod

Locations

Country	Name	City	State
Belgium	Centre for the Evaluation of Vaccination Vaccine & Infectious Disease Institute (VAXINFECTIO) Faculty of Medicine University of Antwerp Belgium	Antwerp
Belgium	Grand Hôpital de Charleroi Site Notre-Dame	Charleroi
Belgium	University Hospitals Leuven	Leuven
Belgium	Regionaal Ziekenhuis Heilig Hart Tienen Hospital	Tienen	Vlaams Brabant
Finland	Helsinki University Central Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Tampereen yliopistollinen sairaala Hospital	Tampere
France	CHU Amiens Hopital Sud	Amiens
France	Hôpital Saint Jacques	Besançon
France	GORH, CHU Estaing	Clermont-Ferrand
France	CHU Dijon	Dijon
France	Hôpital Jeanne de Flandre CHU de Lille	Lille
France	CHU de Nîmes - Hopital Universitaire Caremeau	Nîmes
France	Centre d'Investigation Clinique de Vaccinologie Cochin Pasteur (CIC BT505)	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU de Reims Institut Alix de Champagne	Reims
France	Hôpital de Hautepierre	Strasbourg
Germany	Charité - Universitätsmedizin Berlin Hospital	Berlin
Germany	Universitätsklinikum Erlangen Hospital	Erlangen
Germany	Elisabeth Krankenhaus Essen GmbH - Clinic/Outpatient Facility	Essen
Germany	Klinikum der Friedrich Schiller Universität Jena Hospital	Jena
Germany	LMU Klinikum der Universität- Hospital	München
Germany	Klinikum Wolfsburg Hospital	Wolfsburg
Netherlands	Center Gynaecological Oncology Amsterdam AMC, NKI-AVL, VUmc	Amsterdam
Netherlands	St. Antonius Ziekenhuis Hospital	Nieuwegein
Spain	Hospital Clinic Dept of Obstetrics and Gynecology C/ Villarroel Unidad de Ginecología Oncológica, Instituto Clínico de Ginecología y Obstetricia y Neonatología (ICGON), Hospital Clínic, Instituto de Investigaciones Biomédi	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Vall D Hebron	Barcelona
Spain	Institut Catala d'Oncologia L'Hopitalet de Llobregat	Barcelona
Spain	Clinica Ginecologica Ceoga, Clinic/Outpatient Facility	Lugo
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital La Paz de Madrid	Madrid
Spain	Hospital Universitario "12 de Octubre"	Madrid
Spain	Hospital Regional Universitario Carlos Haya - Hospital Materno Infantil	Malaga
Spain	Hospital Sagrado Corazón de Sevilla	Sevilla
United Kingdom	Dumfries and Galloway Royal Infirmary Hospital	Dumfries
United Kingdom	Liverpool - GUM - Liverpool Centre for Sexual Health	Liverpool
United Kingdom	St Mary's Hospital	London
United Kingdom	Academic O&G University of Manchester Research - St Mary's Hospital	Manchester
United Kingdom	The Centre for Immunology and Infection Hull York Medical School University of York	York

Sponsors (1)

Lead Sponsor	Collaborator
Genticel

Countries where clinical trial is conducted

Belgium,  Finland,  France,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clearance of HPV 16 and HPV 18 infection at Month 12 using a type specific, sensitive and quantitative HPV PCR assay.		month 12	No
Secondary	Clearance of HPV 16 and HPV 18 infection.		Month 6, 15, 18, 24	No