LB100 - AVB-114 Treatment of Persistent Crohn’s Disease Perianal Fistulas in the Randomized, Wait-List Controlled STOMP2 Trial

Abstract Podium Presenter(s)

• 

  Phillip Fleshner, MD FASCRS

  Director, Colorectal Surgery Research
  CEDARS SINAI MEDICAL CENTER
  CEDARS SINAI MEDICAL CENTER
  Los Angeles, California, United States

  All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no relevant financial relationships.

Author(s)

• 

  Eric Joseph Dozois, Professor of Surgery

  Chair, Colon and Rectal Surgery
  Mayo Clinic
  Rochester, Minnesota, United States

  All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no relevant financial relationships.
• EE

  Eric Ehman, MD

  Associate Professor
  Mayo Clinic Rochester
  Rochester, Minnesota, United States

  Disclosure information not submitted.
• WF

  William Faubion, Jr., MD

  Dean of Research
  Mayo Clinic
  Phoenix, Arizona, United States

  Disclosure information not submitted.
• DH

  David Hudesman, MD

  Director, IBD Center at NYU Langone Health
  NYU Langone Health
  New York, New York, United States

  Disclosure information not submitted.
• BE

  Benjamin I. Espen, n/a

  Director of Quality Engineering and Data Science
  Avobis Bio, LLC
  Flagstaff, Arizona, United States

  Disclosure information not submitted.
• BP

  Baldeep Pabla, MD, MSCI

  Assistant Professor
  VUMC
  Brentwood, Tennessee, United States

  Disclosure information not submitted.
• KP

  Konstantinos A. Papadakis, MD

  Professor of Medicine
  Mayo Clinic
  Rochester, Minnesota, United States

  Disclosure information not submitted.

Senior Author(s)

• DS

  David A. Schwartz, MD

  Professor of Medicine
  VUMC
  Brentwood, Tennessee, United States

  Disclosure information not submitted.

Purpose/Background: The STOMP2 trial sought to determine whether an implantable autologous cell therapy AVB-114 is effective add-on therapy for patients with persistent Crohn's disease (CD) perianal fistulas. The trial design incorporated wait-list controlled (WLC) elements, allowing eligible control group subjects who completed the 9-month primary endpoint visit to subsequently receive AVB-114 treatment to strengthen the safety and effectiveness estimation.

Methods/Interventions: Eligible patients had a single perianal fistula tract and had failed prior treatment or had documented medication intolerance to biologic or conventional CD therapy. Subjects at 14 U.S. sites were randomized 1:1 to either standard of care (SOC; fistula optimization including seton placement) or AVB-114 implantation. The primary endpoint was combined fistula remission at 9-mo, defined as no collections >2cm on MRI, visual closure of the external opening, and no drainage of fluid despite gentle finger compression. Clinical remission comprised the latter two components. A logistic regression time from exposure model pooled all randomized (RAN) and control group subjects (WLC) who received AVB-114 treatment to estimate all-treated AVB-114 clinical remission through 9-mo.

Results/Outcomes: Baseline clinical features of the patient groups are shown in the Table. Combined fistula remission (using Non-Responder Imputation) was 8.3% (2/24) for SOC and 45.8% (11/24) for RAN AVB-114 (38% difference; 95% CI 11% - 60%; p=0.0078). Twenty SOC subjects were treated with AVB-114 (WLC group). AVB-114 clinical remission between RAN and WLC subjects was similar and together provided narrower estimates with the same coverage (Figure 1). Lower 9-mo perianal disease activity index (PDAI) scores and decreases from baseline were independently associated with an increased probability of clinical remission. Two serious treatment-emergent adverse events (TEAEs; pseudopolyposis and proctalgia) occurred, with the latter attributed to AVB-114. Non-serious product related TEAE were predominantly related to postoperative perianal pain. Two grade 2 (moderate) AEs of cellulitis and abdominal wall abscess were attributed to adipose tissue collection.

Conclusion/Discussion: Both the randomized and all-treated analyses demonstrated substantial AVB-114 effectiveness for CD perianal fistula through 9-mo. AEs were anticipated, and generally mild and infrequent.

Table 1
Demographics and medical/surgical history
Figure 1
Time from exposure model of clinical remission through 9-mo for SOC (N=24), RAN AVB-114 (N=24), WLC AVB-114 (N=20), and ALL AVB-114 (RAN + WLC, N=44). Posterior mean, 95% compatibility interval