DB-3Q bmMSC-EVs in Patients With Perianal Fistulizing Crohn's Disease

A Phase 2a Study of Allogeneic Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicle Isolate Product (DB-3Q) in Patients With Perianal Fistulizing Crohn's Disease

This is a double-blind, randomized, placebo-controlled, sequential cohort, ascending dose clinical trial to evaluate the safety and determine the efficacy of ascending doses of DB-3Q for the treatment of Perianal Fistulizing Crohn's Disease.

Study Overview

• Status: Recruiting
• Conditions: Perianal Fistula Due to Crohn's Disease
• Intervention / Treatment: Biological: Placebo; Biological: DB-3Q

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

Contacts and Locations

• Study Contact: Name: Executive Vice President, Clinical Affairs, MS; Phone Number: 1-800-791-1021; Email: clinicalaffairs@directbiologics.com

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Direct Biologics Investigational Site
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Recruiting
      • Direct Biologics Investigational Site
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center/NYPH
      • Contact: Claudia Musat; Email: cm2065@cumc.columbia.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Direct Biologics Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Direct Biologics Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Written informed consent from participant
2. Men and women 18-75 years of age with a diagnosis of Crohn's Disease for at least six months duration prior to Day 1
3. One or two perianal fistula(s) with 1 or two external openings, that are actively draining
4. Failed at least one medical therapy within the last year including, but not limited to, antibiotics, immunomodulators (6-MP, methotrexate, azathioprine), monoclonal antibodies (adalimumab, certolizumab, golimumab, guselkumab, infliximab, risankizumab, ustekinumab, vedolizumab), or small molecule inhibitors (tofacitinib, upadacitinib)
5. Previous failed surgical intervention, including seton placement at least two weeks prior to screening, or are not candidates for surgical intervention or are not willing to undergo surgical intervention for the management of their fistula
6. Medical therapy for CD stable for at least 2 months prior to Day 1 (Changes in dosing or dosing intervals related to serum drug levels are not permitted)
7. Antibiotics for the treatment of CD (e.g., ciprofloxacin, metronidazole, or rifaximin) must have been stable for at least 2 weeks prior to Day 1
8. Oral corticosteroids ≤ 20 mg/day prednisone or its equivalent and must have been stable for at least 4 weeks prior to Day 1
9. Approval of a screening pelvic MRI by review of a central radiologist. The definition of an acceptable screening pelvic MRI is provided in the study imaging manual.
10. Fulfillment of radiologic inclusion by a central radiologist. Radiologic inclusion on MRI is presence of 1 or 2 qualifying perianal fistula(s). Radiologic inclusion assesses anatomic criteria of a perianal fistula and study-defined imaging endpoint criteria. a. Anatomically, a qualifying perianal fistula on MRI fulfills the following from central radiologist assessment: i. has a communication with the internal sphincter of the anal canal ii. is classified as a Parks intersphincteric, transsphincteric, or suprasphincteric perianal fistula. b. For study imaging endpoints, a central radiologist confirms that a fistula has a minimum score of 7 (range 0 to 25) on MAGNIFI-CD and a fistula fibrosis -to-fluid ratio of less than 80%.25, 37 Within components of MAGNIFI-CD, the fistula has a length of 2.5 cm or greater and has a composition of either 'predominantly fluid/pus' or 'predominantly granulation tissue'. c. Within components of fistula fibrosis-to-fluid ratio, the ratio of hypointense scarring or fibrosis on MRI T2 weighted sequences to hyperintense fluid on MRI T2 weighted sequences is below 80%.25 The fistula is categorized into one of following ranges of fibrosis-to- fluid ratio: i) 0%, ii) 1-19%, iii) 20-39%, iv) 40-59%, or v) 60-79%

Exclusion Criteria

1. Lack of informed consent
2. Pregnant woman, woman of childbearing potential without a documented negative urine or serum pregnancy test, or woman who is breast feeding
3. A participant who is unwilling to use medically acceptable contraception methods during participation in study
4. Active perianal abscess or infection at screening or Day 1
5. Clinically significant medical conditions within six months before Day 1 that would, in the opinion of the Investigator, compromise the safety of the participant
6. Confirmed HIV, Hepatitis B, or Hepatitis C infections
7. History of cancer including melanoma (with the exception of localized non-melanoma skin cancers) within one year of screening
8. History of colorectal cancer within 2 years of screening
9. History of coagulation disorders and/or are currently on anti- coagulant therapy
10. Presence of a recto/ano-vaginal fistula
11. Presence of an ileal anal pouch and/or history of proctectomy
12. Presence of severe proctitis (SES CD >6)
13. Any condition which, in the opinion of the Investigator, would make it unsafe or unsuitable for participant to undergo MRI evaluations (i.e., presence of implantable or external MRI unsafe device that cannot be removed, body weight exceeding limitations, claustrophobia, etc.)

14. The following out of range laboratory results at screening

    • WBC > 13 x 109 /L
    • Hemoglobin < 8 g/dL
    • Platelet count < 100,000/mL
    • AST/ALT > 3 times the upper limit of normal
    • Creatinine > 2 μmol/L
    • PT/INR: 2 times the upper limit of normal
    • Hemoglobin A1c > 6.5 mg/dL
15. Use of investigational therapy or treatment within 30 days prior to Day 1
16. Does not meet the radiologic anatomic inclusion criteria: i) has a primary communication with the rectum and not the anal canal; ii) is classified as a Parks extrasphincteric fistula
17. Does not meet the minimum thresholds for the radiologic imaging endpoint inclusion criteria: i) has a MAGNIFI-CD score of <7 (range 0-6) on screening pelvic MRI; ii) has a fibrosis-to-fluid ratio of 80% or more (range 80-100%) on screening pelvic MRI

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose DB-3Q 15 mL direct injection	Biological: DB-3Q; DB-3Q (IMP) is the frozen liquid formulation of acellular secretome proteins and extracellular vesicles isolated from human bmMSC and processed under current Good Manufacturing Process standards.
Placebo Comparator: Single dose Placebo 15 mL direct injection	Biological: Placebo; 0.9% NaCl
Experimental: Single dose DB-3Q 30 mL direct injection	Biological: DB-3Q; DB-3Q (IMP) is the frozen liquid formulation of acellular secretome proteins and extracellular vesicles isolated from human bmMSC and processed under current Good Manufacturing Process standards.
Placebo Comparator: Single dose Placebo 30 mL direct injection	Biological: Placebo; 0.9% NaCl
Experimental: Single dose DB-3Q 15 ml IV and DB-3Q 30 mL direct injection	Biological: DB-3Q; DB-3Q (IMP) is the frozen liquid formulation of acellular secretome proteins and extracellular vesicles isolated from human bmMSC and processed under current Good Manufacturing Process standards.
Placebo Comparator: Single dose Placebo 15 ml IV and Placebo 30 mL direct injection	Biological: Placebo; 0.9% NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined Remission	Clinically confirmed 100% closure of all treated external openings, without development of new fistulas or abscesses and drainage > 1 cm by the external openings, occurring spontaneously or after gentle finger compression; and on blinded central review of the MRI results, combined imaging endpoint of >50% reduction in MAGNIFI-CD score and >20% increase in perianal fistula fibrosis-to-fluid ratio.	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined Remission	Clinically confirmed 100% closure of all treated external openings, without development of new fistulas or abscesses and drainage > 1 cm by the external openings, occurring spontaneously or after gentle finger compression; and on blinded central review of the MRI results, combined imaging endpoint of >50% reduction in MAGNIFI-CD score and >20% increase in perianal fistula fibrosis-to-fluid ratio.	12 Weeks

Collaborators and Investigators

• Sponsor: Direct Biologics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 2, 2025
• First Submitted That Met QC Criteria: April 2, 2025
• First Posted (Actual): April 9, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Fistula
• Other Study ID Numbers: 3Q-PFCD-201

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No