In this trial story, we look at ANTICIPATE, an observational study that was initiated in 2016 by the COMBACTE-NET’s EFPIA partner Da Volterra, a Paris-based biotechnology company. The primary objective was to determine the incidence of Clostridioides difficile Infection (CDI) in hospitalized patients undergoing oral or intravenous broad-spectrum antibiotic treatments. Other objectives of the study revolved around the analysis of the bacterial diversity and composition of the intestinal microbiome depending on the antibiotic treatment received by the patients.
Beyond ANTICIPATE, the objective of Da Volterra is to develop innovative products to avoid the antibiotic-induced disruption of the microbiome and prevent the life-threatening conditions associations with a disrupted microbiome such CDI. ANTICIPATE was instrumental to streamline the development of DAV132, Da Volterra’s most advanced microbiome-protective therapy designed in particular to protect the microbiome of patients with cancer.
“One of DAV132’s aims is to prevent Clostridium difficile infection, which is often triggered by the use of antibiotics in vulnerable hospitalized patients”Marie-Noëlle Bouverne, Clinical Operations Director at Da Volterra
One thousand microbiomes observed during antibiotic course
The study population involved patients over the age of 50 hospitalized in 34 hospital sites across six European countries (Germany, Greece, France, The Netherlands, Romania, Spain).
Recruitment started in September 2016; in total 2387 patients were screened. Within 13 months, 1007 patients were enrolled and followed up during 3 months to look at the occurrence of CDI and the bacterial diversity and composition of the intestinal microbiome.
Multiple and advanced data analyses, including with machine learning algorithms, were performed by the teams of Da Volterra, UMCU and University of Antwerp. From the trove of clinical data, the main risk factors for CDI were identified and quantified. The research also unveiled smart “microbiome signatures” that can be used to detect whether a patient is at high risk of microbiome-associated diseases such as CDI. This paves to way to diseases predictive tools that may be used in the future by physicians to optimize the care of patients. We are only beginning to understand the complex dynamics of the microbiome, especially when submitted to aggressive (but much needed!) treatments like antibiotics, and its consequences for health. ANTICIPATE has already yielded a lot of knowledge and additional research is ongoing. A patient application has also been filed by the partners in the work.
“ANTICIPATE was an exciting collaboration from start to end and it is inspiring to see what can be derived from the thousand microbiomes we observed over time when submitted to antibiotics. It was a tremendous journey with all our partners and it continues as we envision the translation of the findings into clinically-meaningful innovation for patients.”
Preliminary results were shared at ECCMID 2018 and presented at the COMBACTE networking event during the congress. The team has also submitted the following two articles that have recently been accepted for publication by Nature Communications:
- van Werkhoven CH et al. Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics;
- Berkell et al. Microbiota-based markers predictive of development of Clostridioides difficile
From observational to interventional
In 2020, COMBACTE-NET and Da Volterra started setting up the Phase 3 trial for DAV132. This clinical study, named MICROCARE, aims to demonstrate the efficacy of DAV132 in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome treated with intensive chemotherapy.
The overarching objective of the trial is to demonstrate that DAV132 contributes to decrease the occurrence of life-threatening complications and to reduce the mortality of patients with hematologic malignancies undergoing several cycles of chemotherapies. The primary endpoint will be the occurrence of Clostridioides difficile infection, a severe and life-threatening comorbidity. The study will also assess the efficacy of DAV132 in protecting intestinal microbiome diversity, preventing intestinal colonization with potentially pathogenic bacteria, preventing bloodstream infections and improving Overall Survival.
All the Da Volterra team is working hard to make DAV132 available to physicians to protect the microbiome of their patients in need in a not-so-distant future. DAV132 could well be the first microbiome-protective product to reach patients, it will certainly not be the last.