First Patient With Crohn Disease Dosed in MSC-derived Therapy Trial

The first patient has been dosed in a phase 1 clinical trial (NCT05130983) evaluating Direct Biologics’ ExoFlo, an investigational therapy composed of extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs), for the treatment of medically refractory Crohn disease.¹

ExoFlo is intended to “reduce inflammation, modulate the immune system, and restore tissue through cellular regeneration,” according to the company.

“We are excited to announce the initiation of our Crohn’s disease clinical trial as we expand our ExoFlo clinical development program into inflammatory bowel disease,” Amy Lightner, MD, the chief medical officer of Direct Biologics, said in a statement regarding the news.¹ “Crohn disease is a debilitating lifelong condition that affects every aspect of daily life. With this new trial of ExoFlo, we are seeking to further illustrate the potential anti-inflammatory, immunomodulatory, and regenerative properties of ExoFlo, each of which we believe to be crucial in the treatment of Crohn disease.”

In addition to the Crohn disease clinical trial, it is also being evaluated for the treatment hospitalized adults with acute respiratory distress syndrome (ARDS) caused by COVID-19 in the phase 3 EXTINGUISH COVID-19 clinical trial (NCT05354141), which is currently enrolling patients.² The company also recently announced results from its completed phase 2 trial (NCT04493242) evaluating ExoFlo in that indication. The findings included a significant improvement in mortality at 60 days post-treatment. ExoFlo is also being evaluated for the treatment of ulcerative colitis in a phase 1 clinical trial (NCT05176366) and for the treatment of solid abdominal organ transplantation (NCT05215288) in an expanded access trial.

This ongoing open-label phase 1 clinical trial for Crohn disease is expected to recruit 10 patients aged 18 to 75 years who have had Crohn disease for at least 6 months and who did not respond to treatment with at least 1 monoclonal antibody therapy. Patients who are intolerant to monoclonal antibody therapy or have a contraindication to it may also be included. Participants are required to have medically refractory symptoms and moderately to severely active disease.

Meanwhile, those with fulminant colitis requiring emergency surgery; concurrent active clostridium difficile infection of the colon; concurrent cytomegalovirus infection of the colon; evidence of colonic perforation; massive hemorrhage from the colon requiring emergent surgery in the 6 months prior to screening; ulcerative, indeterminate, microscopic, ischemic, or infectious colitis; neoplasia of the colon; presence of an ostomy; 3 or more prior small bowel resections; previous colonic resection; or a colonic stricture that is unable to pass an adult colonoscope will be excluded from the study. Additional exclusion criteria relate to patient health status, health history, laboratory values, concomitant treatments, and treatment history.

Participants in the trial will be randomly assigned to 1 of 2 treatment arms. Patients in both arms will receive infusions of 15 mL of ExoFloat at Day 0, Day 2, Day 4, Week 2, and Week 6. Afterwards, 1 arm (n=5) will receive 15 mL of ExoFlo every 2 months while the other arm (n=5) will receive 15 mLof ExoFlo monthly. The study's primary end points include safety, defined by the occurrence of serious adverse events (AEs) and treatment-related AEs, and feasibility. The treatment will be considered feasible if no more than 3 participants are incapable of receiving ExoFlo.

The secondary end points will evaluate efficacy with measures including the change in Crohn's Disease Activity Index score, Simple Endoscopic Score for Crohn Disease, Short Form Health Survey, and the EuroQol 5 Dimensions Survey. Pharmacokinetics and pharmacodynamics will be evaluated by changes in C-reactive protein and fecal calprotectin. Treatment failure will be evaluated by the number of participants who experience disease worsening, need for rescue medications or surgical intervention for Crohn disease, or discontinuation of participation because of treatment-related AEs.

REFERENCES
1. Direct Biologics announces initiation of phase 1 clinical trial for medically refractory Crohn’s disease. News release. Direct Biologics, LLC. March 21, 2023. Accessed March 23, 2023. https://directbiologics.com/direct-biologics-announces-initiation-of-phase-1-clinical-trial-for-medically-refractory-crohns-disease/
2. Direct Biologics reports compelling results from phase 2 trial with ExoFlo in hospitalized patients with respiratory failure or moderate-to-severe acute respiratory distress syndrome (ARDS) due to COVID-19. News release. Direct Biologics, LLC. March 14, 2023. Accessed March 23, 2023. https://directbiologics.com/direct-biologics-reports-compelling-results-from-phase-2-trial-with-exoflo-in-hospitalized-patients-with-respiratory-failure-or-moderate-to-severe-acute-respiratory-distress-syndrome-ards-d/