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

Overview

This is an open-label phase1/2, multi-center trial to evaluate the efficacy, safety, tolerability and immunogenicity of INO-3107 in participants with HPV-6 and/or HPV-11 associated recurrent respiratory papillomatosis (RRP). The trial population is divided into two cohorts: Cohort A: Participants with diagnoses of Juvenile-Onset RRP as defined by age at first diagnosis of RRP < 12 years. Cohort B: Participants with Adult-onset RRP as defined by age at first diagnosis of RRP ≥ 12 years. A safety run-in will be performed with up to six participants across cohort A and B with a one week waiting period between each enrolled participant.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 2023

Interventions

  • Drug: INO-3107
    • INO-3107 administered by IM injection followed by EP using CELLECTRA™ 2000 device at Day 0, Week 3, 6, and 9.
  • Device: CELLECTRA™ 2000
    • CELLECTRA™ 2000 device used for EP following IM delivery of INO-3107.

Arms, Groups and Cohorts

  • Experimental: Cohort A and Cohort B
    • Cohort A: Participants with Juvenile-Onset RRP (J-O RRP; age at first diagnosis <12 years) will be administered one injection of INO-3107 intramuscular (IM) injection followed by electroporation (EP) using CELLECTRA™ 2000 at Day 0, Week 3, Week 6, and Week 9. Cohort B: Participants with Adult-Onset RRP (A-O RRP; age at first diagnosis ≥ 12 years) will be administered one injection of INO-3107 intramuscular (IM) injection followed by EP using CELLECTRA™ 2000 at Day 0, Week 3, Week 6, and Week 9.

Clinical Trial Outcome Measures

Primary Measures

  • Number of Participants with at Least a Doubling in the Time Between Surgical Interventions Following First Dose of INO-3107 Relative to the Frequency Prior to the First Dose of INO-3107
    • Time Frame: Screening up to Week 104 (up to approximately 2 years)

Secondary Measures

  • Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
    • Time Frame: Screening up to Week 104 (up to approximately 2 years)
    • An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: 1. Results in death. 2. A life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death. 3. Requires inpatient hospitalization or prolongation of existing hospitalization. 4. Results in persistent or significant disability/incapacity. 5. Results in a congenital anomaly/birth.
  • Change in RRP Staging Assessment Scores Over Time
    • Time Frame: Screening, Day 0, Weeks 6, 11, 26, 52, 78 and 104 (up to approximately 2 years)
    • An RRP Staging Assessment score will be determined using a modified Derkay staging tool. It includes both a subjective functional assessment of clinical parameters and an anatomic assessment of disease distribution. The anatomic score can then be used in combination with the functional score to measure an individual patient’s clinical course and response to the therapy over time.
  • Change from Baseline in Interferon-gamma Enzyme-Linked Immunosorbent Spot (IFN-γ ELISpot) Response Magnitude for IFN-γ Secreting Cells in Peripheral Blood Mononuclear Cells (PBMCs)
    • Time Frame: Baseline, Weeks 6, 9, 11, 26, 52, 78 and 104
  • Change from Baseline in Flow Cytometry Response Magnitude for T-cell Phenotype and Lytic Potential in PBMCs
    • Time Frame: Baseline, Weeks 6, 9, 11, 26, 52, 78 and 104
  • Change from Baseline in Resected Tumor Tissue Response Magnitude for Pro-inflammatory and Immunosuppressive Elements
    • Time Frame: Baseline and at subsequent tissue resections, up to Week 104 (up to approximately 2 years)
  • Change from Baseline in MicroRNA (miRNA) Expression Related to Reduced Frequency of Surgical Intervention
    • Time Frame: Baseline and Week 6

Participating in This Clinical Trial

Key Inclusion Criteria:

  • Histologically-documented HPV-6- or HPV-11-positive respiratory papilloma
  • Requirement for frequent surgical intervention to remove or resect respiratory papilloma, as defined by at least 2 interventions per year for three years prior to Day 0; participants must have a history of at least two surgical procedures during the third year prior to their screening date and during the second year prior to their screening date and at least one surgical procedure with a requirement of a future surgical procedure during the year prior to their screening date
  • 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 :
  • 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 HPV disease (other than surgery or ablation) including but not limited to anti-virals (including cidofovir), radiation, chemotherapy, anti-angiogenic therapy (including bevacizumab), therapeutic vaccination (including Gardasil), or therapy with an experimental agent within 6 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
  • 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Inovio Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jeffrey Skolnik, MD, Study Director, Inovio Pharmaceuticals
  • Overall Contact(s)
    • Inovio Call Center, (267) 440-4237, clinical.trials@inovio.com

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