Clinical trial NCT04398433: INO-3107 With Electroporation (EP) in Participants With HPV-6- and/or HPV-11-Associated Recurrent Respiratory Papillomatosis (RRP)
Official title: 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: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Papillomatosis
Keywords: Human papilloma virus (HPV)
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-05-21
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1/2 open-label, multicenter trial to evaluate the safety, tolerability, immunogenicity, and efficacy of INO-3107 in subjects with HPV-6 and/or 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Screening up to Week 52 (up to approximately 1 year)
Secondary outcomes:
measure: The Number of RRP Surgical Interventions in the 52 Weeks Post Day 0 Compared to the Number of RRP Surgical Interventions in the Year Prior to Day 0 Dosing
timeFrame: Screening up to Week 52 (up to approximately 1 year)
measure: Change in RRP Staging Assessment Scores Over Time
timeFrame: Screening, Day 0, Weeks 6, 11, 26, 52 (up to approximately 1 year)
measure: 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)
timeFrame: Baseline, Weeks 6, 9, 11, 26, 52
measure: Change from Baseline in Flow Cytometry Response Magnitude for T-cell Phenotype and Lytic Potential in PBMCs
timeFrame: Baseline, Weeks 6, 9, 11, 26, 52
measure: Change from Baseline in Resected Tumor Tissue Response Magnitude for Pro-inflammatory and Immunosuppressive Elements
timeFrame: Baseline and at subsequent tissue resections, up to Week 52 (up to approximately 1 year)
measure: Change from Baseline in MicroRNA (miRNA) Expression Related to Reduced Frequency of RRP Surgical Intervention
timeFrame: Baseline and Week 6
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Sacramento
country: United States
facility: University of California at Davis
state: California
city: Atlanta
country: United States
facility: Winship at Emory University Hospital Midtown
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: NYU Langone Voice Center
state: New York
city: Chapel Hill
country: United States
facility: UNC School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Inovio Pharmaceuticals
name: Jeffrey Skolnik, MD
role: STUDY_DIRECTOR
References: