Treatment for HPV16 positive cervical abnormalities

Phase I Clinical Trial Assessing the Safety and Feasibility of Intramuscular pNGVL4aCRTE6E7L2 and TA-CIN Administration for the Treatment of Patients With Persistent HPV16+ ASC-US or LSIL

This study is testing a new DNA and protein vaccine combination to see if it can safely help people with HPV16 positive cervical abnormalities strengthen their immune response.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 19 Years and up
• Sex: Female
• Sponsor: University of Alabama at Birmingham (Academic / other)
• Locations: 2 sites (Birmingham, Alabama and 1 other locations)
• Trial ID: NCT03913117 on ClinicalTrials.gov

What this trial studies

This Phase I clinical trial evaluates the safety and feasibility of a DNA vaccine (pNGVL4aCRTE6E7L2) and a protein vaccine (TA-CIN) for patients with persistent HPV16 positive ASC-US or LSIL. The study aims to determine the appropriate dosage of the DNA vaccine through intra-muscular administration and assess its immunogenicity and toxicity. Participants will receive the DNA vaccine followed by a boost with the TA-CIN protein vaccine to enhance immune response against HPV16.

Who should consider this trial

Good fit: Ideal candidates for this study are women aged 19 and older with persistent HPV16 positive ASC-US or LSIL for more than six months.

Not a fit: Patients with cervical abnormalities not associated with HPV16 or those with severe underlying health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with HPV16 related cervical abnormalities, potentially reducing the risk of progression to cervical cancer.

How similar studies have performed: Other studies have explored HPV vaccines, but this specific approach using a DNA vaccine combined with a protein boost is novel and has not been extensively tested.

Eligibility criteria

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.

Where this trial is running

Birmingham, Alabama and 1 other locations

• UAB | The University of Alabama at Birmingham — Birmingham, Alabama, United States (Recruiting)
• Johns Hopkins University — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Study coordinator: Wendy Wu, MS

Conditions ASC-US; LSIL; HPV16