Safety, Tolerability, and Immunogenicity of GTL001 Vaccine Adjuvanted With Imiquimod Cream in HPV 16- and/or HPV 18-Infected Women Aged 25 to 65 Years, With Normal Cytology, ASCUS, or LSIL
Safety, Tolerability, and Immunogenicity of GTL001 Vaccine Adjuvanted With Imiquimod Cream in HPV 16- and/or HPV 18-Infected Women Aged 25 to 65 Years, With Normal Cytology, ASCUS, or LSIL
A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, and Immunogenicity of
 GTL001 Vaccine Adjuvanted With Imiquimod Cream in HPV 16- and/or HPV 18-Infected Women Aged
 25 to 65 Years, With Normal Cytology, ASCUS, or LSIL.
This is an outpatient, open-label study. After a screening period of up to 4 weeks, all
 eligible subjects will receive 2 doses, 6 weeks apart, of GTL001 Powder reconstituted with
 water for injection. GTL001 will be adjuvanted with Aldara, 5% imiquimod cream, applied to
 the injection site 15 minutes and 24 hours after each vaccination. The follow-up period is 12
 weeks from the first injection. The duration of the study is defined for each subject as the
 date that signed, written informed consent is provided through the last follow-up visit.
 Total duration of subject participation is approximately 16 weeks.
Inclusion Criteria:

 1. Females between the ages of 25 and 65 years, inclusive, at the time of screening.

 2. Subject is in generally good health based on medical history and on clinically
 acceptable results, in the judgment of the investigator, on the following assessments:
 physical examination, vital signs, clinical chemistry, and hematology.

 3. Cervical HPV 16 and/or 18 infection confirmed by cobas® HPV Test (Roche Molecular
 Systems, Inc) real-time polymerase chain reaction (RT PCR) assay at screening.

 4. Cervical cytological evaluation with a normal, ASCUS, or LSIL result.

 5. Subjects of childbearing potential must use effective contraception at the time of
 GTL001 injection and for at least 12 months after the first vaccination. Effective
 methods of birth control include those that result in a low failure rate (ie, less
 than 1% per year) when used consistently and correctly, such as implants, injectable,
 combined oral contraceptives, desogestrel only pill, levonorgestrel-releasing
 intrauterine system, intrauterine devices, vasectomized partner, and true sexual
 abstinence. Subjects not of childbearing potential include those who are surgically
 sterile or postmenopausal (no menses for the previous 12 months).

 6. Subject is capable of understanding the written informed consent, provides signed and
 witnessed written informed consent, and agrees to comply with protocol requirements.

 7. In the opinion of the investigator, the subject is able to comply with the protocol
 and has a high probability of completing the study.

 Exclusion Criteria:

 1. Current or history of untreated high-grade cervical lesion (either CIN2 or CIN3).

 2. Current or history of cervical, vulvar, or vaginal cancer.

 3. Prior exposure to HPV prophylactic vaccine, regardless of number of doses received, or
 participation in another HPV vaccination clinical trial.

 4. Current acute or chronic disease, other than HPV 16/18 infection, which would be
 expected to interfere with the protocol-defined evaluations.

 5. Clinically significant gynecological abnormalities that could interfere with study
 procedures (eg, prolapse, severe vaginal atrophy, myoma, hysterectomy) in the judgment
 of the investigator.

 6. Malignancy, or treatment for malignancy, within the previous 2 years, with the
 exception of basal cell or squamous cell carcinoma of the skin.

 7. Clinically important abnormalities in the physical examination or laboratory tests
 during the screening period (ie, hemoglobin level <9.5 g/dL, white blood cells <2500
 cells/mm3, aspartate aminotransferase and/or alanine aminotransferase ≥1.5 × the upper
 limit of normal [ULN], creatinine ≥1.25 × ULN, alkaline phosphatase ≥2 × ULN, and
 total bilirubin >ULN).

 8. Administration of any live viral vaccine within 3 months or any inactivated (nonlive)
 vaccine within 2 weeks prior to screening.

 9. Primary or secondary systemic immunosuppression (defined as prolonged [≥7 days] use of
 corticosteroids that is ≥20 mg/day of prednisone equivalent or any other
 immunosuppressive drug).

 10. History of severe allergy requiring hospital care or history of severe asthma
 requiring oral or parenteral drug management in the last year.

 11. Known hypersensitivity to imiquimod.

 12. History of a severe reaction to any drug or vaccination.

 13. Medical condition with clinical and/or biological consequences judged by the
 investigator to be incompatible with ID vaccination.

 14. History of, or positive test results at screening for, human immunodeficiency virus,
 hepatitis B virus surface Ag, or hepatitis C virus.

 15. Current episode of symptomatic vaginal or genital infection.

 16. Current episode or history of genital herpes.

 17. Subject is pregnant or lactating/breastfeeding.

 18. Use of any investigational drug within 30 days before screening or current
 participation in another clinical trial.

 19. History of recent (within 1 year) alcohol/drug abuse.

 20. Employee or family member of the investigator or study site personnel.

 21. Enrollment goals have been reached in the subject's age cohort