Phase II Study of HPV Therapeutic Vaccine in HPV Infected Women With Normal Cytology or ASCUS/LSIL (RHEIA-VAC)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Genticel Identifier:
First received: October 4, 2013
Last updated: November 20, 2014
Last verified: November 2014

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.

Condition Intervention Phase
Genital Infection Viral
Biological: ProCervix
Biological: Placebo
Phase 2

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

Further study details as provided by Genticel:

Primary Outcome Measures:
  • Clearance of HPV 16 and HPV 18 infection at Month 12 using a type specific, sensitive and quantitative HPV PCR assay. [ Time Frame: month 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clearance of HPV 16 and HPV 18 infection. [ Time Frame: Month 6, 15, 18, 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 220
Study Start Date: December 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HPV therapeutic vaccine
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
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 Comparator: Placebo matching ProCervix
Placebo matching ProCervix and adjuvanted by Aldara™, a cream containing 5% of imiquimod
Biological: Placebo
Placebo matching ProCervix and adjuvanted by Aldara™, a cream containing 5% of imiquimod


Ages Eligible for Study:   25 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.
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Please refer to this study by its identifier: NCT01957878

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Responsible Party: Genticel Identifier: NCT01957878     History of Changes
Other Study ID Numbers: PC10VAC02 
Study First Received: October 4, 2013
Last Updated: November 20, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Finland: Finnish National Agency for Medicines
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Paul-Ehrlich-Institut
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Virus Diseases processed this record on February 04, 2016