Study of ExoFlo for the Treatment of Perianal Fistulas

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 cohorts of 12 subjects as follows:

Cohort 1: Local injection of 15 mL of IMP or NS on Day 0 (8 IMP, 4 NS)

• ExoFlo (Biological): Local injection of bone marrow mesenchymal stem cell derived extracellular vesicles
• Local injection of normal saline (Other): Placebo

Primary outcomes

• Adverse Events [3 Months]

Sex: All, ages: 18 Years to 75 Years

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

Participant flow

Outcome results

• Adverse Events (Primary), Count of participants, Participants: Cohort 1: Placebo 1; Cohort 1: Treatment 3

Adverse events

Time frame: 3 Months

Other adverse events by term

Limitations and caveats: The very small sample size limits the interpretability of the results.

• Study Protocol and Statistical Analysis Plan (PDF, 2023-06-02)

• Bill Arana, Study director, Direct Biologics, LLC