A Prospective, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of VGX-3100 Delivered Intramuscularly Followed by Electroporation With CELLECTRA™ 5PSP for the Treatment of HPV-16 and/or HPV-18 Related High Grade Squamous Intraepithelial Lesion (HSIL) of the Cervix
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 203
- 试验地点
- 53
- 主要终点
- Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples
研究概览
简要总结
HPV-303 is a prospective, randomized, double-blind, placebo-controlled study of VGX-3100 delivered intramuscularly (IM) followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed high-grade squamous intraepithelial lesions (HSIL) (cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) of the cervix, associated with human papillomavirus (HPV-16) and/or HPV-18.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 18 years and above
- •Confirmed cervical infection with HPV types 16 and/or 18 at screening
- •Cervical tissue specimen/slides provided to Study Pathology Adjudication Committee for diagnosis scheduled to be collected within 10 weeks prior to anticipated date of first dose of study drug
- •Confirmed histologic evidence of cervical HSIL at screening
- •Must be judged by Investigator to be an appropriate candidate for the protocol-specified procedure required at Week 36
- •With respect to their reproductive capacity must be post-menopausal or surgically sterile or willing to use a contraceptive method with failure rate of less than 1% per year when used consistently and correctly from screening until Week 36
- •Normal screening electrocardiogram (ECG)
排除标准
- •Microscopic or gross evidence of adenocarcinoma-in-situ (AIS), high grade vulvar, vaginal, or anal intraepithelial neoplasia or invasive cancer in any histopathologic specimen at screening
- •Cervical lesion(s) that cannot be fully visualized on colposcopy
- •History of endocervical curettage (ECC) which showed cervical HSIL indeterminate, or insufficient for diagnosis
- •Treatment for cervical HSIL within 4 weeks prior to screening
- •Pregnant, breastfeeding or considering becoming pregnant during the study
- •History of previous therapeutic HPV vaccination
- •Immunosuppression as a result of underlying illness or treatment
- •Receipt of any non-study, non-live vaccine within 2 weeks of Day 0
- •Receipt of any non-study, live vaccine within 4 weeks of Day 0
- •Current or history of clinically significant, medically unstable disease or condition which, in the judgment of the investigator, would jeopardize the safety of the participant, interfere with study assessments or endpoint evaluation, or otherwise impact the validity of the study results
- •Presence of acute or chronic bleeding or clotting disorder that would contraindicate IM injections, or use of blood thinners within 2 weeks of Day 0
- •Participation in an interventional study with an investigational compound or device within 30 days of signing informed consent
- •Less than two acceptable sites available for IM injection
研究组 & 干预措施
VGX-3100 + EP
Participants received 3 IM injections of 6 mg (in 1 mL) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.
干预措施: VGX-3100 (Biological)
VGX-3100 + EP
Participants received 3 IM injections of 6 mg (in 1 mL) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.
干预措施: CELLECTRA™-5PSP (Device)
Matched Placebo + EP
Participants received 3 IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.
干预措施: Matched Placebo (Biological)
Matched Placebo + EP
Participants received 3 IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.
干预措施: CELLECTRA™-5PSP (Device)
结局指标
主要结局
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples
时间窗: At Week 36
Baseline biomarker-positive participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at Week 36, and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or low-grade intraepithelial lesion (LSIL). Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
次要结局
- mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody(At Week 15 and Week 36)
- Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)(From Baseline to Week 40)
- Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36(Baseline; Week 15 and Week 36)
- Safety Population: Number of Participants With Local and Systemic AEs(From Baseline to Week 40)
- Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])(From Baseline to Week 40)
- Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)(From Baseline to Week 40)
- ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples(At Week 36)
- Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample(At Week 36)
- ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample(At Week 36)
- Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing(At Week 36)
- mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36(Baseline; Week 15 and Week 36)
- ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing(At Week 36)
- Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample(At Week 36)
- ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample(At Week 36)
- Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing(At Week 36)
- ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing(At Week 36)
- Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma(From Baseline at Week 36)
- ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma(From Baseline at Week 36)
- Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations(From Baseline at Week 36)
- ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations(From Baseline at Week 36)
- Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody(At Week 15 and Week 36)
- Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15(Baseline, Week 15)
- mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15(Baseline, Week 15)