A Phase II study to assess the safety and efficacy of AVB-114 in treatment of complex Crohn's perianal fistulas in subjects with quiescent rectal disease and whose fistula has failed to respond to biologic or conventional therapy. Combined remission of treated perianal fistula in the investigational treatment arm will be compared to a standard of care control arm. The study has 2 parts: Part 1: All required study visits for subjects who initially receive study treatment and those who receive standard of care therapy (control arm). Part 2: Subjects who are enrolled in the control arm may receive treatment with AVB-114 following week 36. Those subjects then will be followed as specified in the clinical protocol.
AVB-114 is an investigational therapy which offers a new therapeutic approach to treating this unmet medical need. The drug product is a mesenchymal cell substrate system comprised of autologous mesenchymal cells incubated with a 3-dimensional bioabsorbable substrate. The drug substance is expanded, pure mesenchymal stem cells (MSC) which are known to modulate local inflammation and orchestrate tissue healing. By incubating cells with a 3-dimensional bioabsorbable substrate designed for anal fistula geometry, cells are locally delivered into the fistula tract to promote healing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
60
This treatment consists of inserting a seton (a soft flexible tube or nonabsorbable string) into the subject's perianal fistula. The seton will be removed by a study doctor at study visits as applicable.
AVB-114 consists of stem cells taken from a subject's fat tissue seeded into a bioabsorbable plug. AVB-114 will be inserted into the subject's fistula by a study doctor on Day 0.
Mayo Clinic Arizona
Phoenix, Arizona, United States
Office of Phillip Fleshner, MD
Los Angeles, California, United States
Stanford University
Redwood City, California, United States
UC Davis
Sacramento, California, United States
University of Colorado School of Medicine
Aurora, Colorado, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
UChicago Medicine and Biological Sciences
Chicago, Illinois, United States
Indiana University Health University Hospital
Indianapolis, Indiana, United States
Mass Gen Hospital
Boston, Massachusetts, United States
...and 5 more locations
Change in proportions of subjects with combined remission of treated perianal fistula between the AVB-114 and standard of care groups.
Time frame: 36 weeks
Change in proportions of subjects with fistula clinical remission between the AVB-114 and standard of care groups.
Time frame: Week 12 to Week 104
Change in the means of durability of clinical remission between the AVB-114 and standard of care groups.
Length of time fistula meets clinical remission definition.
Time frame: Week 12 to Week 104
Change in means of time to clinical remission between the AVB-114 and standard of care groups.
Time frame: Week 12 to Week 104
Change in proportions of subjects with fistula relapse between the AVB-114 and standard of care groups.
Time frame: Week 12 to Week 104
Change in means of time to fistula relapse between the AVB-114 and standard of care groups.
Time frame: Week 12 to Week 104
Change in proportions of radiologic response of treated fistula between the AVB-114 and standard of care groups.
Time frame: Baseline, Week 12 to Week 52
Change in means of disease activity index scores using the Perianal Disease Activity Index (PDAI) between the AVB-114 and standard of care groups.
Perianal Disease Activity Index (PDAI). Possible scores range from 0-20, with a higher score indicating more severe perianal disease activity
Time frame: Baseline, Week 36
Change in means of disease activity index scores using the short Crohn's Disease Activity Index (sCDAI) between the AVB-114 and standard of care groups.
Short Crohn's Disease Activity Index (sCDAI). Possible scores range from 44 to \>450, with a higher score representing more severe disease activity
Time frame: Baseline, Week 36
Change in means of patient quality of life assessment scores using the Euroqol 5 Diumention 5, level measure of health status (Eq-5Q-5L) between the AVB-114 and standard of care groups.
Euroqol 5 Dimension 5, level measure of health status (EQ-5D-5L). The scale ranges in scores from 0 to 100, with a higher score indicating a more severe health status.
Time frame: Baseline, Week 36
Change in means of patient quality of life assessment scores using the Inflammatory Bowel Disease Questionnaire (IBDQ) between the AVB-114 and standard of care groups.
Inflammatory Bowel Disease Questionnaire (IBDQ). Possible scores range from 32-224, with a higher score indicating a better health-related quality of life.
Time frame: Baseline, Week 36
Change in patient assessment of impact to daily functionality related to treated fistula between the AVB-114 and standard of care groups.
Days of missed work or activity and reason why will be captured.
Time frame: Baseline, Week 12 to Week 36
Change in the evaluations of patient care trajectory related to treated fistula between the AVB-114 and standard of care groups.
Number and type of healthcare resources utilized will be captured.
Time frame: Week 12 to Week 36
Change in number of adverse events between the AVB-114 and standard of care groups.
Time frame: Day 1 to Week 104
Change in number of serious adverse events between the AVB-114 and standard of care groups.
Time frame: Day 1 to Week 104
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