Clinical trial NCT01957878: Phase II Study of HPV Therapeutic Vaccine in HPV Infected Women With Normal Cytology or ASCUS/LSIL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Genital Infection Viral
HUMAN PAPILLOMA VIRUS
Lead sponsor: Genticel
Sponsor class: INDUSTRY
First posted: 2013-10-08
Enrollment: 239
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clearance of HPV 16 and HPV 18 infection at Month 12 using a type specific, sensitive and quantitative HPV PCR assay.
timeFrame: month 12
Secondary outcomes:
measure: Clearance of HPV 16 and HPV 18 infection.
timeFrame: Month 6, 15, 18, 24
Other outcomes:
Locations:
city: Tienen
country: Belgium
facility: Regionaal Ziekenhuis Heilig Hart Tienen Hospital
state: Vlaams Brabant
city: Antwerp
country: Belgium
facility: Centre for the Evaluation of Vaccination Vaccine & Infectious Disease Institute (VAXINFECTIO) Faculty of Medicine University of Antwerp Belgium
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi Site Notre-Dame
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala Hospital
city: Amiens
country: France
facility: CHU Amiens Hopital Sud
city: Besançon
country: France
facility: Hôpital Saint Jacques
city: Clermont-Ferrand
country: France
facility: GORH, CHU Estaing
city: Dijon
country: France
facility: CHU Dijon
city: Lille
country: France
facility: Hôpital Jeanne de Flandre CHU de Lille
city: Nîmes
country: France
facility: CHU de Nîmes - Hopital Universitaire Caremeau
city: Paris
country: France
facility: Centre d'Investigation Clinique de Vaccinologie Cochin Pasteur (CIC BT505)
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Reims
country: France
facility: CHU de Reims Institut Alix de Champagne
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin Hospital
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen Hospital
city: Essen
country: Germany
facility: Elisabeth Krankenhaus Essen GmbH - Clinic/Outpatient Facility
city: Jena
country: Germany
facility: Klinikum der Friedrich Schiller Universität Jena Hospital
city: München
country: Germany
facility: LMU Klinikum der Universität- Hospital
city: Wolfsburg
country: Germany
facility: Klinikum Wolfsburg Hospital
city: Amsterdam
country: Netherlands
facility: Center Gynaecological Oncology Amsterdam AMC, NKI-AVL, VUmc
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis Hospital
city: Barcelona
country: Spain
facility: 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
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D Hebron
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia L'Hopitalet de Llobregat
city: Lugo
country: Spain
facility: Clinica Ginecologica Ceoga, Clinic/Outpatient Facility
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital La Paz de Madrid
city: Madrid
country: Spain
facility: Hospital Universitario "12 de Octubre"
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya - Hospital Materno Infantil
city: Sevilla
country: Spain
facility: Hospital Sagrado Corazón de Sevilla
city: Dumfries
country: United Kingdom
facility: Dumfries and Galloway Royal Infirmary Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool - GUM - Liverpool Centre for Sexual Health
city: London
country: United Kingdom
facility: St Mary's Hospital
city: Manchester
country: United Kingdom
facility: Academic O&G University of Manchester Research - St Mary's Hospital
city: York
country: United Kingdom
facility: The Centre for Immunology and Infection Hull York Medical School University of York
Study officials:
References: