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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ventral Hernia; Abdominal Hernia
• Intervention / Treatment: Drug: BOTOX Dose A; Drug: BOTOX Dose B; Drug: Placebo for BOTOX; Drug: BOTOX Dose C

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• United States
  • New York
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital-Long Island /ID# 251280
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Atrium Health Carolinas Medical Center /ID# 247711

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

11

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Estimated): December 29, 2023
• Primary Completion (Estimated): April 22, 2025
• Study Completion (Estimated): May 19, 2025

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 7, 2022

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: OnabotulinumtoxinA; Abdomen; BOTOX; Primary fascial closure
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Hernia; Hernia, Ventral; Hernia, Abdominal; Internal Hernia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: M21-779

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes