Study of Treatment for HPV16+ ASC-US or LSIL

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Биопрепарат pNGVL4aCRTE6E7L2
  Naked pNGVL4aCRTE6E7L2 DNA plasmid
• Биопрепарат TA-CIN
  TA-CIN is a single fusion protein comprised of HPV16 L2, E7 and E6 proteins linked in tandem.

Первичные конечные точки

• Safety and feasibility of pNGVL4aCRTE6E7L2 DNA vaccination [Срок оценки: 12 months]
• Dose finding [Срок оценки: 12 months]
• Safety and feasibility of PVX-6 vaccination [Срок оценки: 12 months]

Вторичные конечные точки (5)

• HPV16 antibody response [Срок оценки: 12 months]
• HPV16 CD8 T cell response [Срок оценки: 12 months]
• HPV16 L2E7E6 T cell proliferative response [Срок оценки: 12 months]
• Clearance of HPV16 [Срок оценки: 12 months]
• Cytologic clearance [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Patients with persistent (>6 month period) ASC-US/LSIL determined by cervical cytology at study entry (ThinPrep with imaging)
• 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.
• Age ≥ 19 years
• Baseline Eastern Cooperative Oncology Group
• 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
• 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.
• Ability to understand and the willingness to sign a written informed consent document.
• Subject is able to adhere to the study visit schedule and other protocol requirements.

Критерии исключения

• Patients with ASC-US/LSIL determined by cervical cytology at study entry that are HPV16 negative.
• Histologic evidence of CIN2+
• Patients with a diagnosis of immunosuppression or prolonged, active use of immunosuppressive medications such as steroids.
• Prior vaccination with any HPV antigen (prophylactic or therapeutic).
• Patients who are receiving any other investigational agents within 28 days prior to the first dose.
• 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.
• Patients with a history of autoimmune disease such as multiple sclerosis, exclusive of a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease.
• Patients with a history of allergic reactions attributed to compounds used in agent preparation.
• Patients who are pregnant or breast feeding.
• Patient with active or chronic infection of HIV, HCV, or HBV.
• Patients who have had a prior LEEP or cervical conization procedure.
• 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.
• Inability to understand or unwillingness to sign an informed consent document.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• UAB | The University of Alabama at Birmingham — Birmingham
• Johns Hopkins University — Baltimore

Идентификаторы

NCT: NCT03913117 · BB IND 18340 · 000540585

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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