Perianal Fistula, Crohn's Disease
Conditions
Keywords
Perianal Fistula, Perianal Fistulizing Crohn's Disease
Brief summary
To evaluate the safety and feasibility of ExoFlo as a treatment for Perianal Fistulizing Crohn's Disease.
Detailed description
This is a phase IB/IIA, multicenter, single-blind, placebo-controlled, dose-escalation design, randomized controlled trial for the treatment of Perianal Fistulizing Crohn's Disease. Subjects will be randomized 2:1 Investigational Medicinal Product (IMP) to normal saline (NS) in 3 cohorts of 12 subjects as follows: Cohort 1: Local injection of 15 mL of IMP or NS on Day 0 (8 IMP, 4 NS) Cohort 2: Local injection of 30 mL of IMP or NS on Day 0 (8 IMP, 4 NS) Cohort 3: Local injection of 30 mL of IMP or NS on Day 0 and Month 3 (8 IMP, 4 NS)
Interventions
BIOLOGICALExoFlo
Local injection of bone marrow mesenchymal stem cell derived extracellular vesicles
OTHERLocal injection of normal saline
Placebo
Sponsors
Direct Biologics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Single-blind
Intervention model description
Multicenter, Placebo-controlled, Dose-escalation Design, Randomized Controlled Trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Men and Women 18-75 years of age with a diagnosis of Crohn's Disease (CD) for at least six months duration. 2. Single and/or Multi-tract Perianal fistula(s). 3. Failed at least one medical therapy within the last year including, but not limited to, antibiotics, immunomodulators (6-MP, methotrexate, azathioprine), monoclonal antibodies (infliximab, adalimumab, certolizumab, ustekinumab, golimumab, vedolizumab), or small molecule inhibitors. 4. Previous failed surgical intervention, including seton placement at least two weeks prior, or are not candidates for surgical intervention or are not willing to undergo surgical intervention for the management of their fistula. 5. Medical therapy for CD stable for at least 2 months prior to administration of IMP. Changes in dosing or dosing intervals related to serum drug levels are permitted. 6. Ability to comply with protocol. 7. Competent and able to provide written informed consent.
Exclusion criteria
1. Active perianal abscess or infection at the time of screening, enrollment, or at the time of investigational product administration 2. Clinically significant medical conditions within the six months before administration of IMP that would, in the opinion of the investigators, compromise the safety of the subject. 3. History of cancer including melanoma (with the exception of localized skin cancers) within one year of screening. 4. History of colorectal cancer within 2 years 5. Subjects who have a diagnosis of coagulation disorders and/or are currently on anti-coagulant therapy 6. Investigational drug within one month of treatment 7. Pregnant or breast feeding or trying to become pregnant. 8. Presence of a rectovaginal fistula 9. Presence of an ileal anal pouch and/or history of proctectomy 10. The presence of severe proctitis 11. Any condition which, in the opinion of the investigator, would make it unsafe or unsuitable for patients to undergo Magnetic Resonance (MR) evaluations (i.e., presence of implantable or external MR unsafe device that cannot be removed, body weight exceeding limitations, claustrophobia etc.). 12. A participant who is unwilling to use medically acceptable contraception methods during participation in study 13. The following out of range laboratory results at screening (result may be repeated) * WBC \>11 x 109 /L * Hemoglobin \< 8 g/dl * Platelet count \<100,000/mL * AST/ALT \>2 times the upper limit of normal * Creatinine \>2 umol/L * PT/INR: outside normal limits * Hemoglobin A1c\>6.5 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Feasibility | 12 Months | Safety will be defined as the rate of Adverse Events (AEs) or Severe Adverse Events (SAEs) related to IMP and administration of IMP in this patient population. Safety and feasibility will be evaluated for one dose of 15 mL or 30 mL ExoFlo or two doses of 30 mL ExoFlo in subjects with perianal fistula(s) in the setting of Crohn's Disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Healing | 12 Months | To evaluate the efficacy for one dose of 15 mL or 30 mL ExoFlo or two doses of 30 mL ExoFlo in subjects with perianal fistula(s) in the setting of Crohn's Disease. Subjects will be evaluated for healing progress: complete healing, partial healing, lack of response, or treatment failure. |
Countries
United States
Outcome results
None listed