Clinical trial NCT05836883: Study of ExoFlo for the Treatment of Perianal Fistulas
Official title: A Phase IB/IIA Study of ExoFlo, an Ex Vivo Culture-expanded Adult Allogeneic Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicle Isolate Product, for the Treatment of Perianal Fistulizing Crohn's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Perianal Fistula
Crohn's Disease
Keywords: Perianal Fistula
Perianal Fistulizing Crohn's Disease
Lead sponsor: Direct Biologics, LLC
Sponsor class: INDUSTRY
First posted: 2023-05-01
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Multicenter, Placebo-controlled, Dose-escalation Design, Randomized Controlled Trial.
Primary purpose: TREATMENT

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)

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Feasibility
timeFrame: 12 Months
Secondary outcomes:
measure: Healing
timeFrame: 12 Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Direct Biologics Investigational Site
state: California
Study officials:
affiliation: Direct Biologics, LLC
name: Bill Arana
role: STUDY_DIRECTOR
References: