Phase I, open-label, sequential-cohort, ascending multiple-dose study to evaluate the safety and tolerability of escalating doses of PDS0101 in female subjects with high-risk HPV infection and biopsy-proven CIN1. The study will include 3 cohorts of 3 to 6 subjects each based on a modified "3 + 3" dose-escalation study design. The study will be initiated with Cohort 1 and progress through Cohort 3, with each subsequent cohort receiving a higher dose of PDS0101. Successive cohorts will receive a constant dose of HPV-16 E6 and E7 peptides. All subjects will receive 3 vaccinations SC given approximately 21 days apart. Dosing and dose escalation will be based on safety evaluation for determination of potential dose-limiting toxicity (DLT).
Full Title of Study: “An Open-Label, Phase I, Escalating Dose Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of PDS0101 in Subjects With Cervical Intraepithelial Neoplasia (CIN) and High-risk Human Papillomavirus (HPV) Infection”
- Study Type: Interventional
- Study Design
- Allocation: Non-Randomized
- Intervention Model: Factorial Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Study Primary Completion Date: December 30, 2015
- Biological: R-enantiomer of 1,2-dioleoyl-3-trimethylammonium-propane chloride + Peptides from HPV-16 E6 and E7
Arms, Groups and Cohorts
- Active Comparator: Cohort 1 (Low Dose)
- The group will receive the lowest dose of the vaccine
- Active Comparator: Cohort 2 (Mid Dose)
- The Group will receive the middle dose of the vaccine
- Active Comparator: Cohort 3 (High Dose)
- The Group will receive the highest dose of vaccine to be tested
Clinical Trial Outcome Measures
- Evaluation or determination of adverse events following vaccination
- Time Frame: Days 1-133
Participating in This Clinical Trial
1. Written informed consent prior to initiation of any study-related procedures; 2. Nonlactating female between the ages of 21 to 65 years, inclusive; 3. Non-childbearing potential (defined as surgically sterile or at least 2 years postmenopausal) or practicing effective contraception (defined as 2 concurrent methods of contraception, 1 of which is a barrier method) and agrees to continue using effective contraception throughout the duration of the study; 4. Not pregnant based on a negative result on a serum human chorionic gonadotropin (HCG) test at screening Visit 1 and a negative urine pregnancy test prevaccination at Visit 2 (and at subsequent vaccination visits); 5. Pap test documenting atypical squamous cells of undetermined significance (ASCUS)/HPV+, atypical squamous cells high grade (ASC-H), low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL) within 4 months prior to screening Visit 1; 6. History of pathologically confirmed CIN1 by colposcopically-directed punch biopsy, within 12 weeks prior to administration of first study vaccination (CIN 2/3 subjects will not be eligible); 7. For the diagnosis of CIN1, has a documented satisfactory colposcopy, ie, the entire lesion as well as the entire squamocolumnar junction is visualizible by colposcopy; 8. Confirmed high-risk HPV infection by a commercially available high-risk DNA assay (eg, Hybrid Capture II [Qiagen]); 9. Good health with adequate hematologic, renal, hepatic, and cardiac function, as determined by the Investigator, based upon medical history, physical examination, and laboratory test results at the screening visit (Visit 1):
1. Atypical endometrial or glandular cells or evidence of invasive cervical carcinoma on cervical biopsy; 2. Previous history of cancer, other than adequately treated basal cell or Stage 1 squamous cell carcinoma of the skin; 3. Current recognized immunodeficiency disease, including infection with HIV, cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies. 4. Received immunotherapy (eg, IFNs, tumor necrosis factor, interleukins, or biological response modifiers [granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, macrophage colony-stimulating factor]) within 30 days prior to administration of the first study vaccination; 5. Serious, concomitant disorder, including active systemic infection requiring treatment, in the opinion of the investigator; 6. Currently receiving or has received treatment with systemic steroids in the following dosages within 30 days prior to administration of the first study vaccination.
Gender Eligibility: Female
Minimum Age: 21 Years
Maximum Age: 65 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- PDS Biotechnology Corp.
- Provider of Information About this Clinical Study
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