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)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 17
- 主要终点
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: CELLECTRA® 2000 (Device)
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.
干预措施: CELLECTRA® 2000 (Device)
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.
干预措施: CELLECTRA® 2000 (Device)
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.
干预措施: INO-3107 (Drug)
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.
干预措施: INO-3107 (Drug)
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.
干预措施: INO-3107 (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 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.
Percentage of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
时间窗: From first dose of study drug through 30 days following the last dose (approximately up to Week 13)
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.
次要结局
- Change from Baseline in MicroRNA (miRNA) Expression Related to Reduced Frequency of RRP Surgical Intervention(Baseline and Week 6)
- 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))
- Change in RRP Staging Assessment Scores Over Time(Screening, Day 0, Weeks 6, 11, 26, 52 (up to approximately 1 year))
- Change from Baseline in Flow Cytometry Response Magnitude for T-cell Phenotype and Lytic Potential in PBMCs(Baseline, Weeks 6, 9, 11, 26, 52)
- 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)(Baseline, Weeks 6, 9, 11, 26, 52)
- 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))
- 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(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)(Baseline, Weeks 6, 9, 11, 26, and 52)
- Change in Flow Cytometry Response Magnitude for T-cell Phenotype and Lytic Potential in PBMCs(Baseline, Weeks 6, 9, 11, 26, and 52)
- Pro-inflammatory Elements in Resected Tumor Tissues Assessed by Ribo-nucleic Acid (RNA) Sequencing(Baseline, up to Week 52)