This is a Phase 1/2 open-label, multicenter trial to evaluate the safety, tolerability, immunogenicity, and efficacy of INO-3107 in participants with human papilloma virus type 6 (HPV-6) and/or type 11 (HPV-11)-associated recurrent respiratory papillomatosis (RRP). The trial population will include participants who have been diagnosed with either Juvenile-Onset RRP (J-O RRP) as defined by age at first diagnosis \<12 years or with Adult- Onset RRP (A-O RRP) as defined by age at first diagnosis ≥12 years. A safety run-in will be performed with up to six participants with a one week waiting period between each enrolled participant.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
INO-3107 administered by IM injection.
CELLECTRA® 2000 device used for EP following IM delivery of INO-3107.
Mayo Clinic Arizona
Phoenix, Arizona, United States
University of California at Davis
Sacramento, California, United States
Winship at Emory University Hospital Midtown
Atlanta, Georgia, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Washington University School of Medicine
St Louis, Missouri, United States
NYU Langone Voice Center
New York, New York, United States
UNC School of Medicine
Chapel Hill, North Carolina, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, United States
UT Southwestern Medical Center
Dallas, Texas, United States
...and 1 more locations
Percentage of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in congenital anomaly or birth defect, or was considered an important medical event. TEAEs were defined for this trial as any AEs that occurred following Day 0 following administration of study drug (IM + EP), until 30 days following the last dose. TEAEs included both serious and non-serious TEAEs.
Time frame: From first dose of study drug through 30 days following the last dose (approximately up to Week 13)
Change in Number of Recurrent Respiratory Papillomatosis (RRP) Surgical Interventions in One Year Following Day 0, Compared to One Year Prior to Day 0
Time frame: Up to Week 52
Percentage of Participants by Percent Reduction in RRP Surgical Interventions Post Baseline Compared to Prior Year
Time frame: Up to Week 52
Change From Baseline in RRP Staging Assessment Scores Over Time
RRP staging assessment score was determined using a modified Derkay staging tool. It included both a subjective functional assessment of clinical parameters and an anatomic assessment of disease distribution. The anatomic score was then used in combination with the functional score to measure an individual participant's clinical course and response to the therapy over time. The score ranges from 0-179, where a higher score indicates worse disease. Baseline is defined as the most recent measurement prior to the first (Day 0) dose. Total Site Score + Total Symptom Score = Total Clinical Score.
Time frame: Baseline, Weeks 6, 11, 26, and 52
Change in Interferon-gamma Enzyme-Linked Immunosorbent Spot (IFN-γ ELISpot) Response Magnitude for IFN-γ Secreting Cells in Peripheral Blood Mononuclear Cells (PBMCs)
Whole blood samples were collected and PBMCs were isolated to be tested for T-lymphocytes producing interferon-gamma (IFN-γ) in response to the human papilloma virus (HPV) types 6E6+6E7, and 11E6+11E7 antigens. The antigen-specific cellular immune response to INO-3107 was measured in spot-forming units per million peripheral blood mononuclear cells (SFU/10\^6, PBMC) using ELISpot for this outcome measure (OM).
Time frame: Baseline, Weeks 6, 9, 11, 26, and 52
Change in Flow Cytometry Response Magnitude for T-cell Phenotype and Lytic Potential in PBMCs
Cellular immune activity was measured using flow cytometry for the purposes of performing a lytic granule loading assay, which analyzed the intracellular markers involved in lytic degranulation and cytotoxic potential: Granzyme A (GrzA), Granzyme B (GrzB), Granulysin, and Perforin (Prf). Subtypes of CD8 T-cells: CD8 HPV-6 CD38+GrzA+GrzB+Prf+, CD8 HPV-11 CD38+GrzA+GrzB+Prf+, CD8 HPV-6 Ki67+GrzA+GrzB+Prf+, and CD8 HPV-11 Ki67+GrzA+GrzB+Prf+, subtypes of CD4 T-cells - CD4 HPV-6 CD38+, CD4 HPV-11 CD38+, CD4 HPV-6 Ki67+, and CD4 HPV-11 Ki67+ are reported.
Time frame: Baseline, Weeks 6, 9, 11, 26, and 52
Pro-inflammatory Elements in Resected Tumor Tissues Assessed by Ribo-nucleic Acid (RNA) Sequencing
Pro-inflammatory elements:granulysin (GNLY),C-X-C motif chemokine receptor 6(CXCR6),C-C motif chemokine receptor 5(CCR5),CXCR3, granzyme A(GZMA),interferon regulatory factor1(IRF1),integrin subunit alpha 1(ITGA1),lymphocyte-specific protein tyrosine kinase(LCK),natural killer cell granule protein 7(NKG7),perforin-1(PRF1),eomesodermin(EOMES),CD3 delta subunit of T cell receptor complex(CD3D),CD3 epsilon subunit of T cell receptor complex(CD3E),\&CD8 subunit alpha(CD8A) in papilloma tissues are reported. Reads that mapped to transcript of each gene were counted to measure expression levels for genes from each sample. Raw counts per gene were generated. Counts per million (CPM) mapped reads were calculated \& globally normalized across samples using trimmed mean of M values (TMM).
Time frame: Baseline, up to Week 52
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