Study of Treatment for HPV16+ ASC-US or LSIL

Phase 1

Recruiting

• Conditions: LSIL; ASC-US
• Interventions: Biological: pNGVL4aCRTE6E7L2; Biological: TA-CIN

• Registration Number: NCT03913117
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

Phase I clinical trial to assess safety of pNGVL4aCRTE6E7L2 DNA and TA-CIN protein vaccinations, and to seek the appropriate dose of the pNGVL4aCRTE6E7L2 DNA vaccine

Detailed Description

Primary Objectives

1. To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL.

2. To determine the appropriate intra-muscular injection dose of pNGVL4aCRTE6E7L2 DNA vaccine as determined by toxicity and immunogenicity for a subsequent phase II clinical trial.

3. To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with persistent HPV16+ ASC-US/LSIL.

Study Timeline

• Study First Submitted: 2019-04-10
• Study First Submitted QC: 2019-04-10
• Study First Posted: 2019-04-12
• Study Start: 2023-07-10
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-29
• Last Update Posted: 2025-01-30
• Primary Completion: 2025-05
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

1. Patients with persistent (>6 month period) ASC-US/LSIL determined by cervical cytology at study entry (ThinPrep with imaging)

2. Patients whose cytologic samples are persistent (>6 month period) HPV16+ by Roche Cobas 4800, Roche Linear Array HPV Genotyping test or other FDA-approved HPV genotyping test at study entry. Co-infections with HPV types other than HPV16 are permissible for study entry.

3. Age ≥ 19 years

4. Baseline Eastern Cooperative Oncology Group

5. Patients must have adequate organ function at the time of enrollment as defined by the following parameters:

   • White blood cell count > 3,000
   • Absolute lymphocyte number > 500
   • Absolute neutrophil count > 1,000
   • Platelets > 90,000
   • Hemoglobulin > 9
   • Total bilirubin <3 X the institutional limit of normal
   • AST(SGOT)/ALT(SGPT) <3 X the institutional limit of normal
   • Creatinine < 2.5X the institutional limit of normal

6. Women of child-bearing potential must agree to use two forms of contraception (hormonal and barrier) prior to study entry and for 3 months after study completion.

7. Ability to understand and the willingness to sign a written informed consent document.

8. Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria

1. Patients with ASC-US/LSIL determined by cervical cytology at study entry that are HPV16 negative.
2. Histologic evidence of CIN2+
3. Patients with a diagnosis of immunosuppression or prolonged, active use of immunosuppressive medications such as steroids.
4. Prior vaccination with any HPV antigen (prophylactic or therapeutic).
5. Patients who are receiving any other investigational agents within 28 days prior to the first dose.
6. Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Patients with a history of autoimmune disease such as multiple sclerosis, exclusive of a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease.
8. Patients with a history of allergic reactions attributed to compounds used in agent preparation.
9. Patients who are pregnant or breast feeding.
10. Patient with active or chronic infection of HIV, HCV, or HBV.
11. Patients who have had a prior LEEP or cervical conization procedure.
12. History of prior malignancy permitted if patient has been disease free for ≥ 5 years; however individuals with completely resected basal cell or squamous cell carcinoma of the skin within this interval may be enrolled.
13. Inability to understand or unwillingness to sign an informed consent document.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
pNGVL4aCRTE6E7L2 3 mg dose	pNGVL4aCRTE6E7L2	High dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
pNGVL4aCRTE6E7L2 0.3mg dose	pNGVL4aCRTE6E7L2	Low dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
PVX-6	pNGVL4aCRTE6E7L2	Selected dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0 and 4, and the TA-CIN protein is administered by intramuscular injection at week 8.
pNGVL4aCRTE6E7L2 1 mg dose	pNGVL4aCRTE6E7L2	Intermediate dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
PVX-6	TA-CIN	Selected dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0 and 4, and the TA-CIN protein is administered by intramuscular injection at week 8.

Primary Outcome Measures

Name	Time	Method
Dose finding	12 months	To determine the appropriate intra-muscular injection dose of pNGVL4aCRTE6E7L2 DNA vaccine as determined by toxicity and immunogenicity for a subsequent phase II clinical trial
Safety and feasibility of pNGVL4aCRTE6E7L2 DNA vaccination	12 months	To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL
Safety and feasibility of PVX-6 vaccination	12 months	To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with persistent HPV16+ ASC-US/LSIL

Secondary Outcome Measures

Name	Time	Method
HPV16 CD8 T cell response	12 months	To evaluate the levels of circulating HPV-16 E6- and E7-specific CD8+ T cells and T regulatory cells in the peripheral blood pre- and post-vaccination
HPV16 L2E7E6 T cell proliferative response	12 months	To evaluate the proliferative responses of peripheral blood mononucleocytes pre- and post-vaccination in response to stimulation by HPV16 E6, E7 and L2
Cytologic clearance	12 months	To evaluate changes in the cytopathology of ectocervical and endocervical specimens taken pre- and post-vaccination
HPV16 antibody response	12 months	To evaluate the levels of circulating antibody specific for HPV-16 in the peripheral blood pre- and post-vaccination
Clearance of HPV16	12 months	To evaluate the presence of high risk HPV, and specifically HPV16 in cytologic specimens pre- and post-vaccination

Trial Locations

Locations (2)

UAB | The University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States