INO-3107 With Electroporation (EP) in Participants With HPV-6- and/or HPV-11-Associated Recurrent Respiratory Papillomatosis (RRP)

An Open-label Multi-center Study of INO-3107 With Electroporation (EP) in Subjects With HPV-6- and/or HPV-11-associated Recurrent Respiratory Papillomatosis (RRP)

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 Overview

• Status: Completed
• Conditions: Respiratory Papillomatosis
• Intervention / Treatment: Drug: INO-3107; Device: CELLECTRA® 2000

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Sacramento, California, United States, 95817
      • University of California at Davis
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Winship at Emory University Hospital Midtown
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Voice Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77005
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Histologically-documented HPV-6- or HPV-11-positive respiratory papilloma or documentation of low-risk positive HPV using a Sponsor approved HPV-6/11 type-specific assay
• Requirement for frequent RRP intervention to remove or resect respiratory papilloma, as defined as at least two RRP surgical (including laser) interventions in the year prior to and including Day 0
• Must be an appropriate candidate for upcoming surgical intervention as per Investigator judgment and RRP Staging Assessment score
• Adequate bone marrow, hepatic, and renal function

• Participants must meet one of the below requirements:

  • Be of non-child bearing potential (≥12 months of non-therapy-induced amenorrhea, confirmed by follicle-stimulating hormone [FSH], if not on hormone replacement)
  • Be surgically sterile (vasectomy in males or absence of ovaries and/or uterus in females)
  • Agree to use one highly effective or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and at least through week 12 after last dose
  • Agree to abstinence from penile-vaginal intercourse, when this is the participant's preferred and usual lifestyle

Key Exclusion Criteria:

• Recipient of therapy directed towards RRP disease (other than surgery or ablation) including but not limited to anti-virals (including cidofovir), radiation, chemotherapy, anti-angiogenic therapy (including bevacizumab), prophylactic HPV vaccination (including Gardasil) as therapeutic intervention, or therapy with an experimental agent within 3 months prior to Day 0
• Ongoing or recent (within 1 year) evidence of autoimmune disease that required treatment with systemic immunosuppressive treatments, with the exception of: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that requires only hormone replacement, or psoriasis that does not require systemic treatment
• Diagnosis of immunodeficiency or treatment with systemic immunosuppressive therapy within 28 days prior to the first dose of trial treatment, including systemic corticosteroids
• High risk of bleeding or require the use of anticoagulants for management of a known bleeding diathesis
• Recipient of any live virus vaccine within 4 weeks prior to the first dose of trial treatment or any non-live vaccine within two weeks prior to the first dose of trial treatment
• History of clinically significant, medically unstable disease which, in the judgment of the Investigator, would jeopardize the safety of the participant, interfere with trial assessment or evaluation, or otherwise impact the validity of the trial results
• Fewer than two acceptable sites are available for IM injection considering the deltoid and anterolateral quadriceps muscles. Study treatment should not be given within 2 centimeters (cm) of a tattoo, keloid or hypertrophic scar. If there is implanted metal, implanted device, within the same limb the use of the deltoid muscle on the same side of the body is excluded
• Prisoners or participants who are compulsory detained (involuntary incarceration) for treatment of either a psychiatric or physical (i.e. infectious disease) illness
• Any medical or psychological or non-medical condition that might interfere with the participation or safety of the participant, as determined by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INO-3107: Group 1; Participants who had less than or equal to (≤) 2 surgeries received 6.25 milligrams per milliliter (mg/mL) INO-3107, intramuscular (IM) injection, followed by electroporation (EP) using CELLECTRA® 2000 at Day 0, Week 3, Week 6, and Week 9.	Drug: INO-3107; INO-3107 administered by IM injection.; Device: CELLECTRA® 2000; CELLECTRA® 2000 device used for EP following IM delivery of INO-3107.
Experimental: INO-3107: Group 2; Participants who had 3-5 surgeries received 6.25 mg/mL INO-3107, IM injection, followed by EP using CELLECTRA® 2000 at Day 0, Week 3, Week 6, and Week 9.	Drug: INO-3107; INO-3107 administered by IM injection.; Device: CELLECTRA® 2000; CELLECTRA® 2000 device used for EP following IM delivery of INO-3107.
Experimental: INO-3107: Group 3; Participants who had more than or equal to (≥) 6 surgeries received 6.25 mg/mL INO-3107, IM injection, followed by EP using CELLECTRA® 2000 at Day 0, Week 3, Week 6, and Week 9.	Drug: INO-3107; INO-3107 administered by IM injection.; Device: CELLECTRA® 2000; CELLECTRA® 2000 device used for EP following IM delivery of INO-3107.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose of study drug through 30 days following the last dose (approximately up to Week 13)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Number of Recurrent Respiratory Papillomatosis (RRP) Surgical Interventions in One Year Following Day 0, Compared to One Year Prior to Day 0		Up to Week 52
Percentage of Participants by Percent Reduction in RRP Surgical Interventions Post Baseline Compared to Prior Year		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.	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).	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.	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).	Baseline, up to Week 52

Other Outcome Measures

Outcome Measure	Time Frame
MicroRNA (miRNA) Expression Related to Reduced Frequency of RRP Surgical Intervention	Baseline, Week 6

Collaborators and Investigators

• Sponsor: Inovio Pharmaceuticals
• Investigators: Study Director: Jeffrey Skolnik, MD, Inovio Pharmaceuticals

Publications and helpful links

General Publications

• Mau T, Amin MR, Belafsky PC, Best SR, Friedman AD, Klein AM, Lott DG, Paniello RC, Pransky SM, Saba NF, Howard T, Dallas M, Patel A, Morrow MP, Skolnik JM. Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis. Laryngoscope. 2023 Nov;133(11):3087-3093. doi: 10.1002/lary.30749. Epub 2023 May 19.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2020
• Primary Completion (Actual): December 15, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Human papilloma virus (HPV)
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Respiratory Tract Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Neoplasms, Squamous Cell; Urogenital Diseases; Genital Diseases; Recurrent respiratory papillomatosis
• Other Study ID Numbers: RRP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data dictionaries and all collected IPD will be stripped of identifiers and may be made available upon request.
• IPD Sharing Time Frame: Anonymous IPD may be shared following or during the publication of summary data. Archival data may be accessed for up to 10 years following the end of the study.
• IPD Sharing Access Criteria: Those who request the anonymous IPD must provide a plan of study explaining how the data will be used. Requests may be sent to the Central Contact Person. Requests will be reviewed based on the potential for the planned use of the IPD for advancing scientific knowledge and theory.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes