Ex Vivo Culture-expanded Adult Allogeneic Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicle Isolate Product, for the Treatment of Medically Refractory Crohn's Disease

A Phase 2a Study of DB-3Q, an ex Vivo Culture-expanded Adult Allogeneic Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicle Isolate Product, for the Treatment of Medically Refractory Crohn's Disease

This research study is studying DB-3Q as a possible treatment for medically refractory Crohn's disease. The purpose of this study is to research and evaluate safety and effectiveness of the administration of bone marrow mesenchymal stem cell (bmMSC) derived extracellular vesicles product, DB-3Q, the study drug for Crohn's disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Crohn Disease (CD)
• Intervention / Treatment: Other: Placebo; Biological: DB-3Q

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

Contacts and Locations

• Study Contact: Name: Bill Arana; Phone Number: 15123547124; Email: barana@directbiologics.com

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University, St. Louis
      • Contact: Study Coordinator; Phone Number: 314-273-0301; Email: luluhuang@wustl.edu

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. Males and females 18-75 years of age
3. Diagnosed with Crohn's disease of at least 6 months duration with medically refractory symptoms that failed to respond or responded but recurred after one advanced immunologic therapy (must have been receiving at least one advanced immunological therapy for 14 weeks duration prior to screening, including, but not limited to, adalimumab, certolizumab, , infliximab, risankizumab, upadacitinib, ustekinumab and vedolizumab), or is intolerant, or has a contraindication to advanced immunological therapy with a next step of subtotal colectomy or escalation in medical management
4. Active CD as defined by a CDAI score ≥ 220 and/or SES-CD score ≥ 4
5. Exposure to corticosteroids, 5-aminosalicylic acid (5-ASA) drugs, thiopurines, methotrexate, anti-TNF therapy, anti-integrin and anti-interleukin in the past are permitted but a washout period of 8 weeks for any monoclonal antibody is necessary
6. If receiving conventional immunomodulators (i.e., azathioprine [AZA], mercaptopurine [6-MP], or methotrexate [MTX]), must have been taking them for ≥12 weeks, and on a stable dose for at least 4 weeks prior to initial administration of IMP
7. If AZA, 6-MP, or MTX has been recently discontinued, it must have been stopped for at least 4 weeks prior to initial administration of IMP
8. If receiving oral 5-ASA compounds, the dose must have been stable for at least 4 weeks. If receiving oral corticosteroids, the dose must be ≤20 mg/day prednisone or its equivalent and must have been stable for at least 4 weeks prior to initial administration of IMP
9. If receiving budesonide, the dose must have been stable for at least 2 weeks prior to initial administration of IMP
10. If oral 5-ASA compounds or oral corticosteroids (including budesonide) have been recently discontinued, they must have been stopped for at least 2 weeks prior to initial administration of IMP

11. The following medications/therapies must have been discontinued before initial administration of IMP:

    1. Monoclonal therapy (e.g., adalimumab, certolizumab, infliximab, risankizumab, ustenkinumab, and vedolizumab) for at least 8 weeks
    2. Cyclosporine, tacrolimus, or sirolimus, for at least 4 weeks
    3. 6-thioguanine (6-TG) must have been discontinued for at least 4 weeks
    4. JAK inhibitors (e.g., upadacitinib) must have been discontinued for at least 4 weeks
    5. Rectal corticosteroids (i.e., corticosteroids [including budesonide] administered to the rectum or sigmoid colon via foam or enema or suppository) for at least 2 weeks
    6. Rectal 5-ASA compounds (i.e., 5-ASAs administered to the rectum or sigmoid colon via foam or enema or suppository) for at least 2 weeks
    7. Parenteral corticosteroids for at least 2 weeks
    8. Total parenteral nutrition for at least 2 weeks
    9. Antibiotics for the treatment of CD (e.g., ciprofloxacin, metronidazole, or rifaximin) for at least 2 weeks
12. No colonic dysplasia and malignancy as ruled out by colonoscopy within 90 days prior to initial administration of IMP
13. If participant is of reproductive capacity, willing to use adequate birth control measures while in the study

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. Clinically significant medical conditions within the six months before initial administration of IMP: e.g., myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the participant
4. Confirmed Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infections
5. Aspartate aminotransferase (AST) or Alanine transaminase (ALT) greater than 3 times the upper limit of normal at screening

6. Abnormal basic laboratory values with the following cut-offs:

   1. Alkaline phosphate > 200 U/L
   2. WBC >13 109/L
   3. Hemoglobin < 7 g/dL
   4. Platelets < 50 or > 109/L
   5. eGFR < 60 mL/min/1.73m2
   6. HbA1C > 8%
7. Prothrombin time (PT), partial thromboplastin time (aPTT) or international normalized ratio (INR) greater than 1.5 times the upper limits of normal at screening

8. Clinically significant abnormal vital signs prior to initial administration of IMP as defined by:

   1. Systolic blood pressure >160 or <90 mmHg
   2. Diastolic blood pressure >90 or <60 mmHg
   3. Pulse <55 or >105 bpm
   4. Respiratory Rate (RR) <9 and >25 breaths per minute
   5. Temperature >100.4 degrees Fahrenheit
   6. SpO2 <92%
9. History of cancer including melanoma (with the exception of localized skin cancers) within 5 years of study enrollment
10. Ulcerative colitis or indeterminate colitis
11. Suspicion or presence of an intraabdominal or perianal abscess
12. Microscopic, ischemic or infectious colitis
13. Neoplasia of the colon on preoperative biopsy
14. Evidence of colonic perforation
15. Colonic stricture that unable to pass an adult colonoscope
16. Three or more prior small bowel resections
17. Presence of an ostomy
18. Massive hemorrhage from the colon requiring emergent surgery in the 6 months prior to screening
19. Fulminant colitis requiring emergency surgery
20. Concurrent active clostridium difficile infection of the colon
21. Concurrent Cytomegalovirus infection of the colon via colonic biopsy with CMV stain taken within 90 days prior to screening
22. Active or latent tuberculosis
23. Unable to wean off corticosteroids
24. Primary sclerosing cholangitis
25. History of or current alcohol or drug abuse or dependence, recreational use of illicit drugs or prescription medications, or use of medical marijuana within 90 days prior to screening
26. Known allergy to local anesthetics
27. Concurrent use of anticoagulant medications (e.g. warfarin, heparin) or clopidogrel (Plavix)
28. History of known inherited or acquired hypercoagulable states.
29. Electrocardiogram demonstrating cardiac arrhythmia, except for sinus tachycardia within the predefined limit of no greater than 105 bpm.
30. Use of investigational therapy or treatment within 6 months prior to initial IMP administration

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo IV	Other: Placebo; 0.9% Saline
Experimental: DB-3Q 15 mL IV	Biological: DB-3Q; bmMSC derived, extracellular vesicle enriched secretome product
Experimental: DB-3Q 30 mL IV	Biological: DB-3Q; bmMSC derived, extracellular vesicle enriched secretome product
Experimental: DB-3Q 45 mL IV	Biological: DB-3Q; bmMSC derived, extracellular vesicle enriched secretome product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in SES-CD Score	Simple Endoscopic Score for Crohn's Disease (SES-CD) is a standardized tool used by gastroenterologists to assess and quantify the severity of Crohn's disease during an endoscopy or colonoscopy. The scale goes from 0 to greater than 15, with a lower score being better.	12 Weeks

Collaborators and Investigators

• Sponsor: Direct Biologics, LLC

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 3Q-CD-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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