Therapeutic vaccine with objective to clear HPV 16 and 18 genital infections and therefore to prevent cervical pre-cancerous lesions.

• Register: EUCTR
• Last refreshed on: 31 March 2014
• Main ID: EUCTR2013-003358-25-NL
• Date of registration: 17/12/2013
• Prospective Registration: Yes
• Primary sponsor: Genticel
• Public title: Therapeutic vaccine with objective to clear HPV 16 and 18 genital infections and therefore to prevent cervical pre-cancerous lesions.
• Scientific 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 - Phase II study of HPV vaccine in HPV infected women with normal cytology/ASCUS/LSIL
• Date of first enrolment: 18/03/2014
• Target sample size: 222
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003358-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

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

Contacts

• Name: Sylvie Fradet
• Affiliation: PPD

• Name: Sylvie Fradet
• Affiliation: PPD

Key inclusion & exclusion 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 (referring to the time period preceding menopause, excluding perimenopause) and not on hormone replacement therapy (HRT).
3. Subject must have cervical HPV 16 and/or 18 infection confirmed by Riatol realtime polymerase chain reaction (RT-PCR) assay at baseline.
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. Highly effective methods of birth control include those that result in a low failure rate (i.e., less than 1% per year) when used
consistently and correctly such as implants, injectable, combined oral contraceptives, progestogen-only pill, Levenorgestrel-releasing intrauterine system, intra-uterine devices (IUDs), vasectomised partner, condoms with the use of spermicide, sexual abstinence.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 222
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
A subject who meets any of the following exclusion criteria must not be enrolled:
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 to ProCervix, in the judgment of the Investigator.
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 including vaccination with ProCervix.
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 for the following parameters:
- haemoglobin (Hb)
- haematocrit (Hct)
- white blood cell count (WBC)
- lymphocytes
- neutrophils
- eosinophils
- platelet count (plt)
- urea nitrogen (BUN)
- creatinine
- glucose
- alanine aminotransferase (ALT)
- aspartate aminotransferase (AST)
- alkaline phosphatase (ALP)
- total bilirubin (Tbili)
- prothrombin time (PT)
- C-reactive protein (CRP)
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 (defined as prolonged [= 7 days] use of corticosteroids that is greater than or equal to 20 mg of prednisone-equivalent per day or any other immunosuppressive drug).
10. Subject has a history of severe allergy (requiring hospital care) or history of severe asthma requiring oral or parenteral drug management in the last year (treatments with inhaled corticosteroids, short-acting beta agonists [SABA], long-acting beta agonists [LABA] or theophylline are allowed).
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 30days 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 (for example, symptomatic candida infection). If appropriate in the judgment of the Investigator, subjects with symptomatic infection may be treated and reconsidered for enrolment after resolution of the symptomatic 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Women infected by HPV 16 and/or HPV 18 with normal cytology or ASCUS/LSIL
MedDRA version: 16.1 Level: PT Classification code 10064328 Term: Human papilloma virus test positive System Organ Class: 10022891 - Investigations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: ProCervix
Product Code: C16C18-2
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Not available
Current Sponsor code: C16-1
Other descriptive name: recombinant CyaA-HPV16E7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-
INN or Proposed INN: Not available
Current Sponsor code: C18-1
Other descriptive name: recombinant CyaA-HPV18E7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Intradermal use

Trade Name: ALDARA 5% CREAM
Product Name: Imiquimod
Pharmaceutical Form: Cream
INN or Proposed INN: IMIQUIMOD
CAS Number: 99011-02-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: Aqua ad iniectabilia Braun
Product Name: Water for injection
Pharmaceutical Form: Solvent for parenteral use
Other descriptive name: WATER FOR INJECTION
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At month 12 clearance of HPV 16 and 18 infection.

Secondary Objective: 1. To evaluate the efficacy of ProCervix adjuvanted with imiquimod, in comparison with placebo to induce HPV 16 and 18 sustained viral clearance.
2. To evaluate the efficacy of ProCervix adjuvanted with imiquimod, in comparison with placebo , to induce HPV 16 and/or 18 viral clearance at 6, 12, 15, 18 and 24 months.
3. To evaluate the safety and tolerability of ProCervix adjuvanted with imiquimod.

Exploratory (in brief):
1. To assess HPV 16 and/or HPV 18 viral clearance at one or more timepoints up to 12, 18 and 24 months in HPV 16 and/or 18 infected woman.
2. To evaluate the cellular and humoral immunogenicity of ProCervix adjuvanted with imiquimod.
3. To assess regression of cytological abnormalities and histological lesions at 12, 18 and 24 months in subjects with HPV 16 and/or HPV 18-associated ASCUS/LSIL at enrolment.
4. To assess the prevention of progression to CIN2+ in HPV 16 and/or 18 infected women 18 and 24 months after first immunisation.

Primary end point(s): The clearance (non detection of HPV 16 and or HPV18 DNA by RT-PCR at one specific visit) at Month 12 of HPV 16 and HPV 18 infection using a type specific, sensitive and quantitative HPV PCR assay.

Main Objective: To evaluate the efficacy of ProCervix adjuvanted with imiquimod, in comparison with placebo adjuvanted with imiquimod, to induce HPV 16 and 18 viral clearance at 12 months in HPV 16 and/or 18 infected women using a type specific, sensitive and quantitative HPV polymerase chain reaction (PCR) assay.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Months 6, 15, 18 and 24 of infection.
2. Measured on Month 12 and 15 of trial period.
3. Measured on Month 12, 15, 18 and 24 of trial period.
4/5/6. Measured on Month 6, 12, 15, 18 and 24 of trial period.

Safety:
1. 14 days post each vaccination.
2. From vaccination to 12 months
3/4. Study period

Secondary end point(s): Secondary virology endpoints:
1. Clearance at Month 6, 15, 18 and 24 of HPV 16 and HPV 18 infection.
2. Confirmed clearance(non-detection of HPV 16 and/or HPV 18 DNA by RT-PCR on at least two consecutive visits) of HPV 16 and HPV 18 infection.
3. Sustained clearance (non-detection of HPV 16 and/or HPV 18 DNA by RT-PCR at Month 6 or 12 and up to the end of the study) at Month 12 up to the end of the study of HPV 16 and HPV 18 infection.
4. Time to the first clearance of HPV 16 and HPV 18 infection.
5. Duration of the first clearance of HPV 16 and/or HPV 18 infection.
6. Proportion of incident HPV 16 or HPV 18 infections when absent at baseline.

Safety:
1. Occurrence, intensity, duration and relationship of any solicited local and general signs and symptoms during a 14-day follow-up period after each ProCervix or placebo dose.
2. Occurrence, intensity, duration and relationship of unsolicited local and general signs and symptoms occurring until Month 12.
3. Occurrence and relationship of all SAE occurring throughout the study period.
4. Haematologic and biochemical levels outside the normal laboratory ranges at each specified visit.

Secondary ID(s)

2013-003358-25-GB

PC10VAC02

Source(s) of Monetary Support

Genticel