A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions
A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions
This is a Phase II study to evaluate the efficacy and safety of a human papilloma virus (HPV)
 therapeutic vaccine called PepCan (HPV 16 E6 peptides combined with Candida skin testing
 reagent called Candin®) in adult females over a 12 month time period. As the results from the
 Phase I trial demonstrated some efficacy against non-16 HPV types, Candin alone will also be
 tested. Therefore, there will be two treatment arms: (1) PepCan and (2) Candin. Subjects
 found to be eligible for vaccination will be randomized in a double-blinded fashion at a 1:1
 ratio. Each participant will be receiving injections four times with three weeks between
 injections. Clinical and virological responses will be assessed at 6 and 12 months. Safety
 will be assessed from the time of enrollment to 12 Month Visit. Immunological assessments
 will be made at 4 time points (prevaccination, after 2 injections, 6 month after 4 injections
 and 12 months after 4 vaccinations).
This is a single site Phase II clinical trial of PepCan for treating women with biopsy-proven
 HSILs (High Grade Intraepithelial Lesions) randomized and double-blinded to two treatment
 arms. Half of the subjects will receive PepCan, and the other half will receive Candin®
 alone. The study design closely resembles the latest guidelines for treating young women with
 HSIL [14]. Study subjects will be patients attending the UAMS Obstetrics and Gynecology
 Clinics with untreated biopsy-proven HSILs and patients referred from other clinics. Four
 injections (one every 3 weeks) of PepCan or Candin® will be intradermally administered in the
 extremities. Clinical response will be assessed by comparison of colposcopy-guided biopsy
 results obtained prior to vaccination and at 12-Month Visit. Safety will be monitored from
 the time of enrollment through the 12-Month Visit. Blood will be drawn for laboratory testing
 and immunological analyses ("blood test") prior to injection, after the second vaccination, 6
 months after the fourth vaccination, and 12 months after the fourth vaccination. Blood will
 be drawn to aid T-cell analyses ("blood draw") after the first and third vaccinations, and
 possibly at the Optional Follow-Up and/or Optional LEEP visits. HPV-DNA testing will be
 performed at Screening and 6- and 12-Month Visits (Fig. 6). If a subject has persistent HSIL
 at the 12-Month Visit or if a subject is withdrawn due to excessive toxicity, she will be
 given an option to return for a LEEP visit. Alternatively, she may choose to exit the study
 and be followed by a gynecologist for up to 2 years of observation as recommended before
 surgical treatment
Inclusion Criteria:

 -  Aged 18-50 years

 -  Had recent (≤ 60 days) Pap smear result consistent with high grade squamous
 intraepithelial lesion (HSIL) or "cannot rule out HSIL" or HSIL on colposcopy-guided
 biopsy

 -  Untreated for HSIL or "Cannot rule out HSIL"

 -  Able to provide informed consent

 -  Willingness and able to comply with the requirements of the protocol

 Exclusion Criteria:

 -  History of disease or treatment causing immunosuppression (e.g., cancer, human
 immunodeficiency virus, organ transplant, autoimmune disease)

 -  Being pregnant or attempting to be pregnant within the period of study participation

 -  Breast feeding or planning to breast feed within the period of study participation

 -  Allergy to Candida antigen

 -  History of severe asthma requiring emergency room visit or hospitalization within the
 past 5 years

 -  History of invasive squamous cell carcinoma of the cervix

 -  History of having received PepCan

 -  If in the opinion of the Principal Investigator or other Investigators, it is not in
 the best interest of the patient to enter this study