A Study to Evaluate Adverse Events and Effectiveness of OnabotulinumtoxinA in Participants Undergoing Open Abdominal Ventral Hernia Repair for the Achievement of Primary Fascial Closure Without the Use of Component Separation Technique

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Ventral Hernia, Abdominal Hernia

Intervention / Treatment
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* Drug: BOTOX Dose A
* Drug: Placebo for BOTOX
* Drug: BOTOX Dose B
* Drug: BOTOX Dose C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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/m2. 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1, BOTOX Dose A<br>Participants will receive BOTOX Dose A | Drug: BOTOX Dose A<br>* Injection; intramuscular<br>* Other names: OnabotulinumtoxinA;|
| Experimental: Cohort 1, BOTOX Dose B<br>Participants will receive BOTOX Dose B. | Drug: BOTOX Dose B<br>* Injection; intramuscular<br>* Other names: OnabotulinumtoxinA;|
| Placebo Comparator: Cohort 1, Placebo<br>Participants will receive placebo for BOTOX. | Drug: Placebo for BOTOX<br>* Placebo<br>|
| Experimental: Cohort 2, BOTOX Dose A<br>Participants will receive BOTOX Dose A | Drug: BOTOX Dose A<br>* Injection; intramuscular<br>* Other names: OnabotulinumtoxinA;|
| Experimental: Cohort 2, BOTOX Dose B<br>Participants will receive BOTOX Dose B | Drug: BOTOX Dose B<br>* Injection; intramuscular<br>* Other names: OnabotulinumtoxinA;|
| Experimental: Cohort 2, BOTOX Dose C<br>Participants will receive BOTOX Dose C | Drug: BOTOX Dose C<br>* Injection; intramuscular<br>* Other names: OnabotulinumtoxinA;|
| Placebo Comparator: Cohort 2, Placebo<br>Participants will receive placebo for BOTOX | Drug: Placebo for BOTOX<br>* Placebo<br>|
| Experimental: Cohort 3, BOTOX Dose A<br>Participants will receive BOTOX Dose A | Drug: BOTOX Dose A<br>* Injection; intramuscular<br>* Other names: OnabotulinumtoxinA;|
| Experimental: Cohort 3, BOTOX Dose B<br>Participants will receive BOTOX Dose B. | Drug: BOTOX Dose B<br>* Injection; intramuscular<br>* Other names: OnabotulinumtoxinA;|
| Experimental: Cohort 3, BOTOX Dose C<br>Participants will receive BOTOX Dose C. | Drug: BOTOX Dose C<br>* Injection; intramuscular<br>* Other names: OnabotulinumtoxinA;|
| Experimental: Cohort 3, Placebo<br>Participants will receive placebo for BOTOX. | Drug: Placebo for BOTOX<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with achievement of primary fascial closure (PFC) without the use of component separation techniques (CST) in open ventral hernia surgical repair | 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). | Up to 4 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with achievement of PFC | PFC will be defined as the ability to achieve fascia to fascia midline approximation. | Up to 4 Months | 
| Percentage of participants with usage of CST for the purpose of PFC | 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). | 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 | Lateral abdominal wall muscles are released by TAR and external oblique release (unilateral or bilateral) | Up to 4 Months | 
| Change in length of lateral abdominal wall complex | Change in length of lateral abdominal wall complex as measured by abdominal CT scan in supine position prior to surgical repair will be assessed. | Up to 4 Months | 
| Change in Width to the Hernia Defect | Change from screening in width to the hernia defect as measured by abdominal CT scan in supine position prior to surgical repair will be assessed. | Up to 4 Months | 
| Change from screening in length of lateral abdominal wall complex | Change from screening in length of lateral abdominal wall complex as measured by abdominal CT scan performing Valsalva maneuver prior to surgical repair will be assessed. | Up to 4 Months | 
| Change from screening in width to the hernia defect | Change from screening in width to the hernia defect as measured by abdominal CT scan performing Valsalva maneuver prior to surgical repair | Up to 4 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OnabotulinumtoxinA, BOTOX, Abdomen, Primary fascial closure