COMBACTE-NET’s work package 7B is a Phase 3 study recently named MICROCARE. MICROCARE aims to demonstrate the efficacy of DAV132, a microbiota-protective therapy developed by Da Volterra, in preventing the occurrence of Clostridioides difficile infection (CDI) in patients with newly diagnosed Acute Myeloid Leukemia (AML) or high risk Myelodysplatic Syndrome treated with intensive chemotherapy.
The study will determine whether the protection of the intestinal microbiota reduces the incidence of CDI, the colonization by multidrug-resistant bacteria, bacteremia, acute graft-versus-host disease (GvHD), and improves the long-term survival of transplanted patients.
During AML treatment, most patients receive several courses of antibiotics for febrile neutropenia (prophylaxis or empirical treatment) or for suspected or documented bacterial infections. The incidence of CDI, one of the clinical manifestations of microbiota disruption (also called dysbiosis), is high in patients. A study by Amit et al. in 2015 demonstrated that CDI is a predictor of Gram-negative blood stream infections, one of the major complications in AML patients. Furthermore, intestinal dysbiosis, including the decrease in intestinal microbial diversity, is associated with more severe acute GvHD in patients undergoing allo-HSCT.
DAV132 is a colon-targeted adsorbent that binds small molecules like antibiotics and is released in the colon thanks to a special coating. When administered concomitantly with antibiotics, it protects the intestinal microbiota from their damaging effects. The main clinical target DAV132 is developed for multiple indications including prevention of CDI. Extensive preclinical studies, including in vivo models on survival in hamsters with CDI showed that the product was highly successful in preventing antibiotic-induced CDI. The results from randomized clinical trials conducted in healthy volunteers and in patients showed that DAV132 adsorbed residues of antibiotics in the colon and protected the intestinal microbiota from the dysbiosis induced by antibiotics while preserving their bioavailability. DAV132 was safely used in hospitalized patients with concomitant drugs and could be administered in patients taking narrow therapeutic index drugs.
COMBACTE-NET’s ANTICIPATE was an observational study conducted to prepare the design of the interventional study with DAV132. ANTICIPATE confirmed that low gut microbiota diversity is a factor that favors the development of CDI; the low incidence of CDI conducted to look for and select another target population to perform the interventional study.
MICROCARE will be a multicenter study across Europe and North America to recruit 900 patients starting in Q4 2020. At the moment, the evaluation of site eligibility is ongoing at onco-hematological sites and regulatory filings are being prepared
If you are interested in the study, please contact Dr Fabien Vitry, CMO Da Volterra.