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

NCT01957878 | Completed Phase 2 DMC

• 1 other identifier: PC10VAC02
• Study Type: interventional
• Target: 239
• Locations: 7 countries
• Sites: 40

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.

Conditions

Genital Infection Viral; HUMAN PAPILLOMA VIRUS

Outcome Measures

Primary Outcomes (1)

• Clearance of HPV 16 and HPV 18 infection at Month 12 using a type specific, sensitive and quantitative HPV PCR assay.

  month 12

Secondary Outcomes (1)

• Clearance of HPV 16 and HPV 18 infection.

  Month 6, 15, 18, 24

Study Arms (2)

HPV therapeutic vaccine

EXPERIMENTAL

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

Biological: ProCervix

Placebo matching ProCervix

PLACEBO COMPARATOR

Placebo matching ProCervix and adjuvanted by Aldara™, a cream containing 5% of imiquimod

Biological: Placebo

Interventions

ProCervix BIOLOGICAL

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

HPV therapeutic vaccine

Placebo BIOLOGICAL

Placebo matching ProCervix and adjuvanted by Aldara™, a cream containing 5% of imiquimod

Placebo matching ProCervix

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is female between the ages of 25 and 50 years (inclusive).
• Subject is pre-menopausal .
• Subject must have cervical HPV 16 and/or 18 infection confirmed by RT-PCR
• Subject has a cervical cytological evaluation with a normal, ASCUS or LSIL result at baseline.
• 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. .
• Subject is in general good health based on medical history and physical examination.
• Subject is able to communicate effectively with study personnel and is considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.
• Subject voluntarily gives written informed consent to participate in the study.

You may not qualify if:

• 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
• Subject has vaginal atrophy with or without topical hormonal therapies or systemic selective estrogen receptor modulators (SERMs).
• 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
• Current high grade lesions or history of untreated high grade cervical lesion (either CIN2 or CIN3).
• Subject has current or a history of cancer of the cervix.
• 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).
• 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,
• Subject has received any live viral vaccine within 3 months or any other non live vaccine within 2 weeks of first study product administration.
• Subject has primary or secondary systemic immunosuppression
• Subject has a history of severe allergy (requiring hospital care) or history of severe asthma
• Subject has a history of malignant cancer, except the following adequately treated cancers: basal cell carcinoma, or dermatological squamous cell carcinoma.
• Subject was administered with another investigational drug or vaccine within 30 days prior to the screening visit or is participating in any other study.
• Subject has a known hypersensitivity to imiquimod.
• Subject has a history of severe reaction to any drug or vaccination.
• Subject has a medical condition with clinical and/or biological consequences judged by the Investigator incompatible with vaccination(s).

Sponsors & Collaborators

• Genticel: lead

Study Sites (40)

Regionaal Ziekenhuis Heilig Hart Tienen Hospital

Tienen, Vlaams Brabant, Belgium

Location

Centre for the Evaluation of Vaccination Vaccine & Infectious Disease Institute (VAXINFECTIO) Faculty of Medicine University of Antwerp Belgium

Antwerp, Belgium

Location

Grand Hôpital de Charleroi Site Notre-Dame

Charleroi, Belgium

Location

University Hospitals Leuven

Leuven, Belgium

Location

Helsinki University Central Hospital

Helsinki, Finland

Location

Kuopio University Hospital

Kuopio, Finland

Location

Tampereen yliopistollinen sairaala Hospital

Tampere, Finland

Location

CHU Amiens Hopital Sud

Amiens, France

Location

Hôpital Saint Jacques

Besançon, France

Location

GORH, CHU Estaing

Clermont-Ferrand, France

Location

CHU Dijon

Dijon, France

Location

Hôpital Jeanne de Flandre CHU de Lille

Lille, France

Location

CHU de Nîmes - Hopital Universitaire Caremeau

Nîmes, France

Location

Centre d'Investigation Clinique de Vaccinologie Cochin Pasteur (CIC BT505)

Paris, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

CHU de Reims Institut Alix de Champagne

Reims, France

Location

Hôpital de Hautepierre

Strasbourg, France

Location

Charité - Universitätsmedizin Berlin Hospital

Berlin, Germany

Location

Universitätsklinikum Erlangen Hospital

Erlangen, Germany

Location

Elisabeth Krankenhaus Essen GmbH - Clinic/Outpatient Facility

Essen, Germany

Location

Klinikum der Friedrich Schiller Universität Jena Hospital

Jena, Germany

Location

LMU Klinikum der Universität- Hospital

München, Germany

Location

Klinikum Wolfsburg Hospital

Wolfsburg, Germany

Location

Center Gynaecological Oncology Amsterdam AMC, NKI-AVL, VUmc

Amsterdam, Netherlands

Location

St. Antonius Ziekenhuis Hospital

Nieuwegein, Netherlands

Location

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

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitari Vall D Hebron

Barcelona, Spain

Location

Institut Catala d'Oncologia L'Hopitalet de Llobregat

Barcelona, Spain

Location

Clinica Ginecologica Ceoga, Clinic/Outpatient Facility

Lugo, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital La Paz de Madrid

Madrid, Spain

Location

Hospital Universitario "12 de Octubre"

Madrid, Spain

Location

Hospital Regional Universitario Carlos Haya - Hospital Materno Infantil

Málaga, Spain

Location

Hospital Sagrado Corazón de Sevilla

Seville, Spain

Location

Dumfries and Galloway Royal Infirmary Hospital

Dumfries, United Kingdom

Location

Liverpool - GUM - Liverpool Centre for Sexual Health

Liverpool, United Kingdom

Location

St Mary's Hospital

London, United Kingdom

Location

Academic O&G University of Manchester Research - St Mary's Hospital

Manchester, United Kingdom

Location

The Centre for Immunology and Infection Hull York Medical School University of York

York, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2013
• First Posted: October 8, 2013
• Study Start: December 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: December 2, 2016

Record last verified: 2016-12

Locations

ES (10); NL (2); GB (5); DE (6); FI (3); BE (4); FR (10)