Columbia University Irving Medical Center has enrolled the first patient in a multicenter Phase 2 clinical trial investigating the effectiveness of Direct Biologics' proprietary extracellular vesicle technology (DB-3Q, extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells) for the treatment of perianal fistulizing Crohn's Disease.
"Crohn's-related fistulas are very difficult to treat; patients often require multiple surgeries, and the recurrence rates are high with a substantial risk of incontinence" says Marco Bertucci Zoccali, MD, colorectal surgeon and global PI for the study. "This study aims to determine if this approach is a viable option to treat anal fistula in patients with Crohn's disease specifically."
Crohn's disease is an inflammatory bowel disease (IBD) that causes chronic inflammation of the digestive tract. It can cause symptoms like abdominal pain, diarrhea, weight loss, fatigue, strictures (narrowing of the intestines), and fistulas (abnormal connections between organs). A perianal fistula is a tunnel that forms between the anal canal and the skin near the anus, causing pain, leakage, and inflammation/infection of nearby tissues.
Anal fistulas can be treated with surgical procedures – often complex and painful - but recurrence rates are high, especially in people with Crohn's disease. EVs may offer a game-changing avenue for treating autoimmune diseases, with their ability to repair damaged tissues thanks to their anti-inflammatory and immunomodulatory properties.
"The advantages of EVs over traditional stem cell therapies are multiple”, notes Dr. Zoccali. "While derived from stem cells, it is a much more stable product, hence easier to store and administer. It's also less immunogenic, which can mitigate some of the problems associated with stem cell treatment due to the body's response to foreign DNA."
This phase 2 multicenter randomized study will have multiple cohorts with three different doses and administration routes. The first uses an initial dose administered in the operating room via direct injection near the fistula. The second phase will double that dose. The third phase will include local injections and add an IV infusion of the medication.
"These patients are already optimized on their medical therapy for Crohn's" says Dr. Zoccali. "This treatment is for treating the associated fistulas, which has an enormous impact on a patient's quality of life and can cause serious complications. We are very optimistic that this trial will determine the appropriate dosage to help patients with this novel modality."