Study of ExoFlo for the Treatment of Perianal Fistulas

Direct Biologics

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Perianal Fistula; Crohn's Disease

Treatments: Other: Local injection of normal saline; Biological: ExoFlo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05836883

DB-EF-PFCD-1a

Details and patient eligibility

About

To evaluate the safety and feasibility of ExoFlo as a treatment for Perianal Fistulizing Crohn's Disease.

Full 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)

Enrollment: 5 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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5 participants in 6 patient groups, including a placebo group

Cohort 1: Placebo

Placebo Comparator group

Description:

Local injection 15 mL of normal saline on Day 0

Treatment:

Other: Local injection of normal saline

Cohort 2: Placebo

Placebo Comparator group

Description:

Local injection 30 mL of normal saline on Day 0

Treatment:

Other: Local injection of normal saline

Cohort 3: Placebo

Placebo Comparator group

Description:

Local injection 30 mL of normal saline on Day 0 and Month 3

Treatment:

Other: Local injection of normal saline

Cohort 1: Treatment

Experimental group

Description:

Local injection of 15 mL of ExoFlo on Day 0

Treatment:

Biological: ExoFlo

Cohort 2: Treatment

Experimental group

Description:

Local injection of 30 mL of ExoFlo on Day 0

Treatment:

Biological: ExoFlo

Cohort 3: Treatment

Experimental group

Description:

Local injection of 30 mL of ExoFlo on Day 0 and Month 3

Treatment:

Biological: ExoFlo