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

Respiratory Papillomatosis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04398433
• Other study ID #: RRP-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 15, 2020
• Est. completion date: December 15, 2022

Study information

• Verified date: December 2023
• Source: Inovio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 15, 2022
• Est. primary completion date: December 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Papilloma
• Papillomavirus Infections
• Respiratory Papillomatosis
• Respiratory Tract Infections

Intervention

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.

Locations

Country	Name	City	State
United States	Winship at Emory University Hospital Midtown	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
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	Baylor College of Medicine	Houston	Texas
United States	NYU Langone Voice Center	New York	New York
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	University of California at Davis	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Inovio Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Screening up to Week 52 (up to approximately 1 year)
Secondary	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		Screening up to Week 52 (up to approximately 1 year)
Secondary	Change in RRP Staging Assessment Scores Over Time	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.	Screening, Day 0, Weeks 6, 11, 26, 52 (up to approximately 1 year)
Secondary	Change from Baseline in Interferon-gamma Enzyme-Linked Immunosorbent Spot (IFN-? ELISpot) Response Magnitude for IFN-? Secreting Cells in Peripheral Blood Mononuclear Cells (PBMCs)		Baseline, Weeks 6, 9, 11, 26, 52
Secondary	Change from Baseline in Flow Cytometry Response Magnitude for T-cell Phenotype and Lytic Potential in PBMCs		Baseline, Weeks 6, 9, 11, 26, 52
Secondary	Change from Baseline in Resected Tumor Tissue Response Magnitude for Pro-inflammatory and Immunosuppressive Elements		Baseline and at subsequent tissue resections, up to Week 52 (up to approximately 1 year)
Secondary	Change from Baseline in MicroRNA (miRNA) Expression Related to Reduced Frequency of RRP Surgical Intervention		Baseline and Week 6