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

• ClinicalTrials.gov Identifier: NCT04398433
• Recruitment Status: Active, not recruiting
• First Posted: May 21, 2020
• Last Update Posted: May 18, 2023
• Sponsor: Inovio Pharmaceuticals
• Information provided by (Responsible Party): Inovio Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Respiratory Papillomatosis	Drug: INO-3107; Device: CELLECTRA™ 2000	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: June 15, 2020
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: INO-3107; Participants will be administered one 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 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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Screening up to Week 52 (up to approximately 1 year) ]
   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.

Secondary Outcome Measures :

1. 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 [ Time Frame: Screening up to Week 52 (up to approximately 1 year) ]
2. Change in RRP Staging Assessment Scores Over Time [ Time Frame: Screening, Day 0, Weeks 6, 11, 26, 52 (up to approximately 1 year) ]
   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.
3. 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 ]
4. 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 ]
5. 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 52 (up to approximately 1 year) ]
6. Change from Baseline in MicroRNA (miRNA) Expression Related to Reduced Frequency of RRP Surgical Intervention [ Time Frame: Baseline and Week 6 ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Arizona

Phoenix, Arizona, United States, 85054

United States, California

University of California at Davis

Sacramento, California, United States, 95817

United States, Georgia

Winship at Emory University Hospital Midtown

Atlanta, Georgia, United States, 30308

United States, Maryland

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States, 21287

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New York

NYU Langone Voice Center

New York, New York, United States, 10016

United States, North Carolina

UNC School of Medicine

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Cincinnati Children's Hospital

Cincinnati, Ohio, United States, 45229

University of Cincinnati Medical Center

Cincinnati, Ohio, United States, 45267

United States, Texas

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

Baylor College of Medicine

Houston, Texas, United States, 77005

Sponsors and Collaborators

Inovio Pharmaceuticals

Investigators

• Study Director: Jeffrey Skolnik, MD; Inovio Pharmaceuticals

More Information

• Responsible Party: Inovio Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04398433
• Other Study ID Numbers: RRP-001
• First Posted: May 21, 2020
• Last Update Posted: May 18, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data dictionaries and all collected IPD will be stripped of identifiers and may be made available upon request.
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• 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.
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Inovio Pharmaceuticals:

Human papilloma virus (HPV)

Additional relevant MeSH terms:

Respiratory Tract Infections; Papillomavirus Infections; Papilloma; Neoplasms, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Infections; Respiratory Tract Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes