Vanderbilt Clinical Trials

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

Purpose

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.

Condition

Perianal Fistula Due to Crohn's Disease

Eligibility

Eligible Ages: Between 18 Years and 75 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

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

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 Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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 PFCD.
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

Arm	Description	Assigned Intervention
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

Recruiting Locations

Direct Biologics Investigational Site
Nashville, Tennessee 37232

More Details

Status: Recruiting
Sponsor: Direct Biologics, LLC

Study Contact

Executive Vice President, Clinical Affairs, MS
1-800-791-1021
clinicalaffairs@directbiologics.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.