A Phase 2b Double-Blind, Placebo-Controlled, Adaptive, Dose-Escalation Study to Evaluate the Safety and Efficacy of OnabotulinumtoxinA for the Achievement of Primary Fascial Closure Without the Use of Component Separation Technique, in Subjects Undergoing Open Abdominal Ventral Hernia Repair
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 2
- 主要终点
- Percentage of participants with achievement of primary fascial closure (PFC) without the use of component separation techniques (CST) in open ventral hernia surgical repair
研究概览
简要总结
Ventral hernias form when there is a loss of integrity of the abdominal wall muscles. Abdominal hernias can expand and can cause severe pain as the abdominal wall weakens. The purpose of this study is to evaluate the safety and efficacy of a range of onabotulinumtoxinA (BOTOX) doses to achieve primary fascial closure (PFC) without use of component separation technique (CST) in ventral hernia surgical repair.
BOTOX is an investigational drug being developed for the treatment of ventral hernias. In this dose escalation study, participants will be placed in 1 of 3 cohorts. Cohort 1 will be randomized to receive placebo or 1 of 2 BOTOX doses, after which time Cohort 2 will be randomized to receive placebo or 1 of 3 BOTOX doses. Participants in Cohort 3 will be randomized to receive placebo or 1 of 3 BOTOX doses. Adult participants undergoing open abdominal ventral hernia repair will be enrolled. Around 200 participants will be enrolled in the study at approximately 20 sites in the United States.
Participants will receive a single intramuscular injection of BOTOX Dose A, BOTOX Dose B, BOTOX Dose C, or placebo.
There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will be followed for approximately 3 months after surgery and will receive a follow-up phone call 30 days (+/-) their last study visit. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is in good health as determined by medical history, vital signs, and investigator's judgment, including no known active pandemic infection.
- •Body Mass Index (BMI) at screening is <= 40 kg/m
- •Participant meets the following disease activity criteria:
- •Intact abdominal wall muscles (defined as no prior dissection to the lateral abdominal wall complex) based on screening CT scan.
- •Midline ventral hernia requiring surgical repair, at least 6 cm, and not more than 18 cm in transverse defect width at the widest part of the of the hernia defect, as assessed on CT scan by the investigator.
- •Any portion of the ventral hernia does not extend > 3 cm into the M1 subxiphoid zone or into the M5 zone using the 2009 classification by the European Hernia Society.
- •No history of prior onlay hernia mesh wider than rectus.
- •No hernia with loss of domain >20% as determined by the investigator, using Sabbagh method.
排除标准
- •Presence of a medical condition that may put the participant at increased risk with exposure to onabotulinumtoxinA, including diagnosed muscular dystrophy (e.g., Duchenne's muscular dystrophy), myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, mitochondrial disease, or any other significant disease which might interfere with neuromuscular function.
- •Presence or history of any of the following within 3 months prior to the randomization visit that may indicate a vulnerable respiratory state per the investigator's clinical judgment, for example, aspiration pneumonia, lower respiratory tract infections, uncontrolled asthma, severe chronic obstructive pulmonary disease, or otherwise compromised respiratory function.
- •History of ongoing or anticipated need to perform progressive preoperative pneumoperitoneum or other tissue expansion technique for repair of ventral hernia.
- •Planned ostomy reversal, panniculectomy bariatric procedure, or vascular procedure requiring anticoagulants during the study.
- •History of abdominal or hernia repair surgery requiring hospitalization within 6 months prior to screening.
- •History of a contraindication to BOTOX and/or hypersensitivity reactions to BOTOX.
研究组 & 干预措施
Cohort 1, BOTOX Dose A
Participants will receive BOTOX Dose A
干预措施: BOTOX Dose A (Drug)
Cohort 1, BOTOX Dose B
Participants will receive BOTOX Dose B.
干预措施: BOTOX Dose B (Drug)
Cohort 1, Placebo
Participants will receive placebo for BOTOX.
干预措施: Placebo for BOTOX (Drug)
Cohort 2, BOTOX Dose A
Participants will receive BOTOX Dose A
干预措施: BOTOX Dose A (Drug)
Cohort 2, BOTOX Dose B
Participants will receive BOTOX Dose B
干预措施: BOTOX Dose B (Drug)
Cohort 2, BOTOX Dose C
Participants will receive BOTOX Dose C
干预措施: BOTOX Dose C (Drug)
Cohort 2, Placebo
Participants will receive placebo for BOTOX
干预措施: Placebo for BOTOX (Drug)
Cohort 3, BOTOX Dose A
Participants will receive BOTOX Dose A
干预措施: BOTOX Dose A (Drug)
Cohort 3, BOTOX Dose B
Participants will receive BOTOX Dose B.
干预措施: BOTOX Dose B (Drug)
Cohort 3, BOTOX Dose C
Participants will receive BOTOX Dose C.
干预措施: BOTOX Dose C (Drug)
Cohort 3, Placebo
Participants will receive placebo for BOTOX.
干预措施: Placebo for BOTOX (Drug)
结局指标
主要结局
Percentage of participants with achievement of primary fascial closure (PFC) without the use of component separation techniques (CST) in open ventral hernia surgical repair
时间窗: Up to 4 Months
PFC will be defined as the ability to achieve fascia to fascia midline approximation. CST will be defined as the release of the external oblique muscle or the transection of transversus abdominis muscle (known as posterior component separation with transversus abdominis release (TAR).
次要结局
- Change in length of lateral abdominal wall complex(Up to 4 Months)
- Change in Width to the Hernia Defect(Up to 4 Months)
- Change from screening in width to the hernia defect(Up to 4 Months)
- Percentage of participants with achievement of PFC(Up to 4 Months)
- Percentage of participants with usage of CST for the purpose of PFC(Up to 4 Months)
- Number of lateral abdominal wall muscles released among participants who required CST use to achieve PFC as reported by the operating surgeon(Up to 4 Months)
- Change from screening in length of lateral abdominal wall complex(Up to 4 Months)