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

• ClinicalTrials.gov Identifier: NCT05606757
• Recruitment Status: Not yet recruiting
• First Posted: November 7, 2022
• Last Update Posted: October 10, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Ventral Hernia; Abdominal Hernia	Drug: BOTOX Dose A; Drug: Placebo for BOTOX; Drug: BOTOX Dose B; Drug: BOTOX Dose C	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: December 29, 2023
• Estimated Primary Completion Date: April 22, 2025
• Estimated Study Completion Date: May 19, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants with achievement of primary fascial closure (PFC) without the use of component separation techniques (CST) in open ventral hernia surgical repair [ Time Frame: 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).

Secondary Outcome Measures :

1. Percentage of participants with achievement of PFC [ Time Frame: Up to 4 Months ]
   PFC will be defined as the ability to achieve fascia to fascia midline approximation.
2. Percentage of participants with usage of CST for the purpose of PFC [ Time Frame: Up to 4 Months ]
   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).
3. Number of lateral abdominal wall muscles released among participants who required CST use to achieve PFC as reported by the operating surgeon [ Time Frame: Up to 4 Months ]
   Lateral abdominal wall muscles are released by TAR and external oblique release (unilateral or bilateral)
4. Change in length of lateral abdominal wall complex [ Time Frame: Up to 4 Months ]
   Change in length of lateral abdominal wall complex as measured by abdominal CT scan in supine position prior to surgical repair will be assessed.
5. Change in Width to the Hernia Defect [ Time Frame: Up to 4 Months ]
   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.
6. Change from screening in length of lateral abdominal wall complex [ Time Frame: Up to 4 Months ]
   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.
7. Change from screening in width to the hernia defect [ Time Frame: Up to 4 Months ]
   Change from screening in width to the hernia defect as measured by abdominal CT scan performing Valsalva maneuver prior to surgical repair

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

Locations

United States, New York

NYU Langone Hospital-Long Island /ID# 251280

Mineola, New York, United States, 11501

United States, North Carolina

Atrium Health Carolinas Medical Center /ID# 247711

Charlotte, North Carolina, United States, 28203

Sponsors and Collaborators

AbbVie

Investigators

• Study Director: ABBVIE INC.; AbbVie

More Information

Additional Information:

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

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT05606757
• Other Study ID Numbers: M21-779
• First Posted: November 7, 2022
• Last Update Posted: October 10, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• 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/
• URL: https://vivli.org/ourmember/abbvie/

• 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

Keywords provided by AbbVie:

OnabotulinumtoxinA; BOTOX; Abdomen; Primary fascial closure

Additional relevant MeSH terms:

Hernia; Hernia, Ventral; Hernia, Abdominal; Internal Hernia; Pathological Conditions, Anatomical; Botulinum Toxins, Type A; abobotulinumtoxinA; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents