A Study to Evaluate LB1148 for Return of Gastrointestinal Function and Adhesions in Subjects Undergoing Bowel Resection (PROFILE)

A Randomized, Double-Blind, Placebo-Controlled Proof of Concept Study to Evaluate LB1148 for Return of Gastrointestinal Function, Post-Operative Ileus and Intra-Abdominal Adhesions in Subjects Undergoing Elective Bowel Resection

The purpose of this study is to establish preliminary evidence of the efficacy, safety, and tolerability of LB1148 for the treatment of post-operative ileus and intra-abdominal adhesions in subjects undergoing elective bowel resection.

Study Overview

• Status: Recruiting
• Conditions: Ileus; Post-Operative Adhesions
• Intervention / Treatment: Drug: Placebo; Drug: LB1148

Detailed Description

This will be a multicenter, randomized, double-blind, parallel, placebo-controlled, proof-of-concept, adaptive design, Phase 2 study to evaluate LB1148 for return of gastrointestinal function and reduction of post-operative ileus and intra-abdominal adhesions in subjects undergoing elective bowel resection surgery with or without a planned stoma.

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

Contacts and Locations

• Study Contact: Name: Nick McCoy; Phone Number: 214-457-1996; Email: nick.mccoy@palisadebio.com

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36617
      • Recruiting
      • Site 315
  • Arizona
    • Yuma, Arizona, United States, 85364
      • Completed
      • Site 307
  • California
    • Irvine, California, United States, 92868
      • Recruiting
      • Site 329
    • Pasadena, California, United States, 91105
      • Completed
      • Site 310
    • Sylmar, California, United States, 91342
      • Completed
      • Site 302
    • Torrance, California, United States, 90502
      • Completed
      • Site 312
  • Florida
    • Clearwater, Florida, United States, 33756
      • Completed
      • Site 306
    • Miami, Florida, United States, 33125
      • Completed
      • Site 303
    • Miami, Florida, United States, 33126
      • Recruiting
      • Site 331
    • Miami, Florida, United States, 33142
      • Completed
      • Site 305
    • Orlando, Florida, United States, 32804
      • Completed
      • Site 308
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Site 328
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Recruiting
      • Site 321
  • Massachusetts
    • Burlington, Massachusetts, United States, 01850
      • Recruiting
      • Site 324
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Site 325
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Site 317
    • New York, New York, United States, 10075
      • Not yet recruiting
      • Site 323
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • Site 318
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Completed
      • Site 301
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Site 322
    • Wynnewood, Pennsylvania, United States, 19096
      • Not yet recruiting
      • Site 330
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Not yet recruiting
      • Site 327
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • Site 320
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Site 316
    • Houston, Texas, United States, 77024
      • Completed
      • Site 311
    • Houston, Texas, United States, 77030
      • Recruiting
      • Site 319
    • Houston, Texas, United States, 77089
      • Completed
      • Sie 309
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • Site 326

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subjects will be eligible for participation in the study only if they meet ALL of the following inclusion criteria:

1. Scheduled to undergo an elective (non-emergent) bowel resection with a planned stoma via laparotomy or minimally invasive technique. This includes any subject in which a resection of the small intestine, colon, or rectum is performed for any elected indication.
2. Planned stoma takedown or other planned abdominal surgery within 8 months of the initial surgery.
3. Willing to perform and comply with all study procedures including attending clinic visit as scheduled and completion of a second surgery for stoma takedown or other abdominal surgery and to determine the presence of intra-abdominal adhesions.
4. Has been informed of the nature of the study (either the subject or their legal representative), agrees to its provisions, and has provided written informed consent.

Exclusion Criteria:

Subjects will not be eligible for participation in the study if they meet ANY of the following exclusion criteria:

1. <18 or >80 years of age.
2. Requires emergency bowel surgery.

3. Has had 1 or more abdominal surgeries, excluding the current, for inflammatory bowel disease, including, but not limited to, inflammatory bowel disease (IBD), Crohn's Disease, or ulcerative colitis.

   Note: This does not apply to previous surgery such as hernia repair unrelated to IBD.

4. American Society of Anesthesiologists (ASA) Class 4 or 5.
5. Known inability to take the study drug orally (i.e. complete small bowel obstruction).

6. Has contraindications or potential risk factors to taking TXA. These include subjects with:

   1. Known sensitivity to TXA;
   2. Recent craniotomy (past 30 days);
   3. Active cerebrovascular bleed;
   4. Active thromboembolic disease (such as deep vein thrombosis, pulmonary embolism, cerebral thrombosis, ischemic stroke, or acute coronary syndrome);
   5. Acute promyelocytic leukemia taking all-trans retinoic acid for remission induction, or
   6. Continuing use of a combined hormonal contraceptive and or combined hormonal replacement therapy (including combined hormonal pill, patch, or vaginal ring).
7. Has peritoneal carcinomatosis
8. History of or current seizure disorder.
9. Patients with myeloproliferative disorders.
10. Any other condition that, in the opinion of the Investigator, would preclude the subject from being an appropriate candidate for the study, including severe renal or hepatic impairment.
11. Planned treatment with alvimopan (Entereg®) during study participation period.
12. Planned use of 4% icodextrin (Adept®) or SEPRAFILM during the first surgery.
13. Received any other investigational therapy within 4 weeks prior to Randomization
14. Female subjects of childbearing potential with a positive urine or serum pregnancy test or who are not taking (or not willing to take) acceptable birth control measures (abstinence, intrauterine devices, contraceptive implants or barrier methods) through Day 30. Additionally, those women who are lactating and insist on breast feeding within 5 days of the last dose of study drug.
15. Known history of radiation enteritis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; A total of 700 mL of placebo will be administered orally as a split dose before surgery.
Experimental: LB1148; Active	Drug: LB1148; A total of 700 mL of drug product will be administered orally as a split dose before surgery.; Other Names: Active

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in extent and severity of intra-abdominal adhesions among subjects treated with LB1148 or placebo	Extent and severity of intra-abdominal adhesions will be determined by the surgeon using the Intra-Abdominal Adhesion Extent and Severity Assessment Worksheet	up to 8 months from the index surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from surgical closure to resolution or appearance, as appropriate, of 1 or more of the components common to GI dysfunction following elective bowel resection with or without a planned stoma	Compare time from surgical closure to resolution or appearance, as appropriate, of 1 or more of the components common to gastrointestinal (GI) dysfunction following elective bowel resection with a planned stoma.	From surgical closure up to 14 days in hospital
Time to return of gastrointestinal function as defined by achieving GI2	GI2 is a composite endpoint defined as the time from the end of surgery to the time of recovery of the upper GI tract (toleration of solid food) and the time to recovery of the lower GI tract (first bowel movement).	From surgical closure up to 14 days in hospital
Time to Achieve GI-3	GI3 is defined as the toleration of solid food and either first flatus or bowel movement	From surgical closure up to 14 days in hospital
Time to resolution of post-operative ileus	Compare number of hours to resolution of POI.	From surgical closure up to 14 days in hospital
Hospital length of stay	Compare hospital length of stay (LOS, recorded in hours) through Discharge or Day 14 (whichever comes first).	From surgical closure up to 14 days in hospital
Incidence of intra-abdominal adhesions	Compare the incidence of intra-abdominal adhesions following the second surgery among subjects treated with LB1148 or placebo.	up to 8 months from the index surgery

Collaborators and Investigators

• Sponsor: Palisade Bio
• Investigators: Study Director: Bert Slade, MD, Palisade Bio

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: July 14, 2016
• First Posted (Estimate): July 19, 2016

Study Record Updates

• Last Update Posted (Actual): October 31, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Colorectal Surgery; Anastomosis; Enterostomy; Post-operative Ileus; Post-Operative Abdominal Adhesions; Return of Gastrointestinal Function; Enterotomy; Intestines Surgery
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Intestinal Diseases; Fibrosis; Cicatrix; Intestinal Obstruction; Tissue Adhesions; Ileus
• Other Study ID Numbers: LBS-POI-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No