This is a Phase 2, open-label, dose-rising study evaluating the safety, tolerability, and preliminary efficacy of three concentrations of SOR007 ointment (0.15%, 1.0%, and 2.0%) applied topically once per week for four weeks to the ectocervix of subjects with high grade cervical intraepithelial neoplasia (CIN).
In this Phase 2, open-label, dose-rising study, subjects with high grade (CIN 2 or 3) CIN will receive once-weekly topical application of SOR007 ointment to the ectocervix for four weeks. Subjects will be enrolled in three dose-escalating cohorts of three subjects assigned consecutively to receive 0.15%, 1.0%, or 2.0% SOR007 ointment. At the final study visit (Visit 7) subjects will undergo an excision or punch biopsy to record the stage of CIN. PK samples will be obtained post-application on Day 0 at 1, 2, 4, 6, and 24 hours' post-application on Day 1. Additional PK samples will be collected at each visit. Plasma samples for PK analysis on Days 7, 14 and 21 will be collected prior to SOR007 application. The Medical Monitor will review all available data prior to dose escalation. Dose-escalation of SOR007 will be determined by the Medical Monitor. This will be repeated for each escalated dose until all dose levels have been enrolled or a dose is determined unsafe. Safety will be assessed in an ongoing manner and formal safety reviews will be conducted twice for each cohort: after Day 14 and after Day 49 of the last subject in the cohort. If a safety or tolerability issue becomes apparent in a cohort, an additional three subjects will be enrolled at that dose level, for a maximum of six subjects in that cohort. If ≥ 1 safety or tolerability issue occurs in the additional 3 subjects, the prior dose-level will be determined to be the highest dose with an acceptable safety and tolerability profile. If no further safety and tolerability issues are identified in the expanded cohort, dose-escalation will continue. Once the highest dose with an acceptable safety and tolerability profile has been determined by the Medical Monitor, PI, and Sponsor Medical Director, a further 3 subjects will be enrolled to that dose level in order to increase the subject numbers.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
1 mL of SOR007 applied topically to the ectocervix once-weekly for four weeks.
Incidence of treatment emergent adverse events
Treatment emergent adverse events will include all reported adverse events, laboratory assessments, physical examination findings, and vital signs.
Time frame: 49 days
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) of SOR007
Plasma samples for pharmacokinetic (PK) analysis will be obtained on Day 0 at 1, 2, 4, and 6 hours post-application, at 24 hours' post-application (Day 1), and at each subsequent clinic visit (samples on Days 7, 14, and 21 will be obtained prior to dose application).
Time frame: 49 days
Pharmacokinetics: Peak plasma concentration (Cmax) of SOR007
Plasma samples for pharmacokinetic (PK) analysis will be obtained on Day 0 at 1, 2, 4, and 6 hours post-application, at 24 hours' post-application (Day 1), and at each subsequent clinic visit (samples on Days 7, 14, and 21 will be obtained prior to dose application).
Time frame: 49 days
Pharmacokinetics: Time at which peak plasma concentration is observed (Tmax) of SOR007
Plasma samples for pharmacokinetic (PK) analysis will be obtained on Day 0 at 1, 2, 4, and 6 hours post-application, at 24 hours' post-application (Day 1), and at each subsequent clinic visit (samples on Days 7, 14, and 21 will be obtained prior to dose application).
Time frame: 49 days
Regression of CIN
Colposcopic changes as defined by the modified Reid Colposcopic Index (RCI) and confirmed by biopsy histology
Time frame: Baseline and 49 days
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