This is a Phase 1/2 study in patients with a Recurrent Respiratory Papillomatosis (RRP) disease burden that requires repeated surgical procedures for management. RRP is a rare disease caused by the human papillomavirus (HPV). Participants with a pathologically confirmed diagnosis of papilloma and a clinical diagnosis of RRP will be screened for this protocol.
This is a nonrandomized, Phase 1/2 safety and tolerability study. The safety and tolerability of PRGN-2012 will be assessed following two different dose levels during the Phase 1 dose escalation trial. In the Phase 2 portion of the study, treatment with PRGN-2012 at the recommended Phase 2 dose (RP2D) will be used to determine safety and efficacy of PRGN-2012.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
In Phase 1, dose level 1 of the clinical trial, PRGN-2012 is administered at 1 × 10\^11 particle units as adjuvant therapy prior to standard debulking surgery.
In Phase 1, dose level 2 of the clinical trial, PRGN-2012 is administered at 5 × 10\^11 particle units as adjuvant therapy prior to standard debulking surgery.
The Phase 2 portion is designed as a dose expansion study where patients are treated at the RP2D of 5 x 10\^11 PU.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Determine the percentage of subjects with a complete response following treatment with PRGN-2012
A complete response is defined as no requirement for surgical intervention in the 12 months after treatment
Time frame: 1 year
Determine the incidence of dose limiting toxicities to evaluate safety and identify RP2D of PRGN-2012
The incidence of dose limiting toxicities in Phase 1 will be reported per dose level. The dose level at which less than or equal to 1 out of 6 patients experience DLT will be identified as a RP2D.
Time frame: 28 days
Safety of PRGN 2012 at RP2D
Systemic toxicity will be assessed through the capture of Treatment Emergent Adverse Events ( TEAEs) at Phase 1 and Phase 2 patients. The severity of the TEAEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale.
Time frame: 1 year
Immune Responses
Change in HPV-specific T cells post-treatment compared to baseline
Time frame: 1 year
Change in RRP Staging Assessment Scores Over Time
Absolute and percentage change from baseline in Derkay score over time following initiation of PRGN-2012 treatment
Time frame: 1 year
Change in Vocal Function Scores over Time
Absolute and percentage change from baseline in VHI-10 score over time following initiation of PRGN-2012 treatment
Time frame: 1 year
Time to recurrence of papillomatous disease after completion of treatment
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Time to recurrence of papillomatous disease after completion of treatment will be recorded. Time from completion of treatment to first surgery will be assessed.
Time frame: 1 year
Percentage of subjects with reduction in number of surgeries after completion of treatment
The number of surgeries in the 12 months post-treatment will be compared to the number of surgeries in the 12 months pre-treatment to identify subjects that have a reduction in the number of surgeries.
Time frame: 1 year
Number of surgery during the 12 months pre and 12 months post treatment
The number of surgeries in the 12 months post-treatment will be compared to the number of surgeries in the 12 months pre-treatment.
Time frame: 1 year
Overall Response Rate
Determine the percentage of subjects with at least a 50% decrease in the number of surgeries during the 12 month period following completion of PRGN-2012 treatment as compared to the number of surgeries during the 12 months prior to PRGN-2012 treatment initiation.
Time frame: 1 year
Rate of pulmonary RRP partial response in participants with pulmonary disease
The fraction of participants with a pulmonary RRP partial response will be reported in all treated pulmonary participants.
Time frame: 1 year
Rate of pulmonary RRP complete response in participants with pulmonary disease
The fraction of participants with a pulmonary RRP complete response will be reported in all treated pulmonary participants.
Time frame: 1 year