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A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions

Phase 2
Completed
Conditions
Cervical Intraepithelial Neoplasia
Interventions
Biological: PepCan
Biological: Candin®
Registration Number
NCT02481414
Lead Sponsor
University of Arkansas
Brief Summary

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).

Detailed Description

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. Study subjects will be patients attending the University of Arkansas for Medical Sciences (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 Loop Electrosurgical Excision Procedure (LEEP) visits. HPV-DNA testing will be performed at Screening and 6- and 12-Month Visits. 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

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
81
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 (HIV), 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PepCanPepCanFour injections (one every 3 weeks) of PepCan
CandinCandin®Four injections (one every 3 weeks) of Candin
Primary Outcome Measures
NameTimeMethod
Number of Subjects With Complete Response With the Intention-to-treat (ITT) Analysis15 months from time of last vaccination

Histological regression of moderate/severe cervical dysplasia to absence of cervical dysplasia assessed using biopsies (stringent)

Number of Subjects With Complete and Partial Responses With the Per-protocol Analysis15 months from time of last vaccination

Histological regression of moderate/severe cervical dysplasia to mild dysplasia/no dysplasia (lenient) assessed using biopsies, likely avoiding a need for surgery

Number of Subjects With Complete and Partial Responses With the ITT Analysis15 months from time of last vaccination

Histological regression of moderate/severe cervical dysplasia to mild dysplasia/no dysplasia (lenient) assessed using biopsies, likely avoiding a need for surgery

Number of Subjects With Complete Response With the Per-protocol Analysis15 months from time of last vaccination

Histological regression of moderate/severe cervical dysplasia to absence of cervical dysplasia assessed using biopsies (stringent)".

Secondary Outcome Measures
NameTimeMethod
Safety Assessed by Injection-related Adverse Events (AEs)15 months from time of last vaccination

Injection-related AEs occurring in \>5% of injections

Trial Locations

Locations (1)

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

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