Study of ExoFlo for the Treatment of Perianal Fistulas

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

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

Study Overview

• Status: Recruiting
• Conditions: Crohn's Disease; Perianal Fistula
• Intervention / Treatment: Other: Local injection of normal saline; Biological: ExoFlo

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)

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Bill Arana; Phone Number: 1-800-791-1021; Email: clinicalaffairs@directbiologics.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Direct Biologics Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Cohort 1: Placebo; Local injection 15 mL of normal saline on Day 0	Other: Local injection of normal saline; Placebo
Placebo Comparator: Cohort 2: Placebo; Local injection 30 mL of normal saline on Day 0	Other: Local injection of normal saline; Placebo
Placebo Comparator: Cohort 3: Placebo; Local injection 30 mL of normal saline on Day 0 and Month 3	Other: Local injection of normal saline; Placebo
Experimental: Cohort 1: Treatment; Local injection of 15 mL of ExoFlo on Day 0	Biological: ExoFlo; Local injection of bone marrow mesenchymal stem cell derived extracellular vesicles
Experimental: Cohort 2: Treatment; Local injection of 30 mL of ExoFlo on Day 0	Biological: ExoFlo; Local injection of bone marrow mesenchymal stem cell derived extracellular vesicles
Experimental: Cohort 3: Treatment; Local injection of 30 mL of ExoFlo on Day 0 and Month 3	Biological: ExoFlo; Local injection of bone marrow mesenchymal stem cell derived extracellular vesicles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Feasibility	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.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healing	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.	12 Months

Collaborators and Investigators

• Sponsor: Direct Biologics, LLC
• Investigators: Study Director: Bill Arana, Direct Biologics, LLC

Publications and helpful links

Helpful Links

• Direct Biologics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: April 19, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Perianal Fistula; Perianal Fistulizing Crohn's Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Pathological Conditions, Anatomical; Rectal Diseases; Inflammatory Bowel Diseases; Intestinal Fistula; Digestive System Fistula; Fistula; Crohn Disease; Rectal Fistula
• Other Study ID Numbers: DB-EF-PFCD-1a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No