Safety and Efficacy of DAV132 in Patients at High-Risk for Clostridium Difficile Infection (CDI)

A European Multicenter, Randomized, Parallel-group Study to Evaluate the Safety and Efficacy/Performance of DAV132 in Hospitalized Patients at High Risk for Clostridium Difficile Infection and Who Receive Fluoroquinolones for the Treatment of Acute Infections

The purpose of this study is to determine the safe use and evaluate the efficacy/performance of DAV132 in hospitalized patients at high risk for Clostridium difficile infection (CDI) and who receive fluoroquinolones (FQs) for the treatment of acute infections or for prophylaxis of febrile neutropenia.

Da Volterra develops DAV132, a novel therapeutic option preserving the intestinal microbiota, to prevent potentially life-threatening conditions such as CDI or emergence of antibiotic-resistant bacteria. Prevention of CDI remains critical unmet need, especially for patients at high risk of developing such infection.

Inclusion Criteria. Eligible patients for the study must meet ALL the following inclusion criteria:

1. Male or female ≥18 years of age

2. Hospitalized patients requiring a systemic antibiotic treatment for a proven or strongly suspected bacterial infection (lower respiratory tract infection [LRTI], complicated urinary tract infection [cUTI]) or prophylactic treatment of febrile neutropenia for neutropenic patient

3. Patients who are intended to receive one of the following FQs: moxifloxacin, levofloxacin, or ciprofloxacin, by oral or parenteral route, for an intended duration of 5 days (minimum) to 21 days (maximum), in monotherapy

4. Patients expected to stay in hospital for at least 3 days after randomization

5. Patients with the following conditions:

   - Previous history of CDI (no more than 2 episodes) within six months prior to study inclusion

   OR

   - Patient aged ≥65 years, and presenting with at least two of the following:

   • Previous cumulated exposure of at least 5 days to any antibiotics within the last 90 days
   • Patients who have at least one concurrent severe comorbidity among the following: malignant disease, chronic renal failure, cardiopulmonary condition (such as chronic congestive heart failure or severe arterial hypertension), diabetes mellitus, or liver cirrhosis
   • Previous hospitalization of more than 72h within the last 90 days, or patient receiving long-term nursing care for more than one month within the last 90 days

6. Female patients participating in the study must be:

   - of non-childbearing potential: surgically sterilized at least 3 months prior to inclusion, or postmenopausal (menopause is defined as being aged >60 years, or aged between 45 and 60 years and being amenorrheic for ≥2 years)

   OR

   - of childbearing potential, and:

   • using an efficient double contraception from inclusion up to 24 hours after the end of the treatment period: hormonal contraception (including patch, contraceptive ring, etc.), intra-uterine device, or other mechanical contraception method

   AND

   condom, or diaphragm or cervical/vault cap, or spermicide

   AND

   must have a negative urine pregnancy test prior to inclusion to the study.

7. Patients who have given their written informed consent prior to undertaking any study-related procedure.

Exclusion Criteria: Eligible patients for this study will be excluded if any of the following conditions are present:

1. Antibacterial treatment within seven days before randomization
2. Fluoroquinolone indication other than LRTI, cUTI, or febrile neutropenia prophylaxis
3. Patients with suspected or diagnosed CDI at screening, and/or receiving a treatment effective against CDI
4. Patients with diarrhea corresponding to Bristol stool chart types 5-7, combined with a stool frequency of at least three stools in 24 or fewer consecutive hours, regardless of its etiology
5. Patients using probiotics for prevention of CDI and refusing to stop them at inclusion and during the study
6. Patients currently taking activated charcoal
7. Patients who have received a fecal microbial transplantation within the last 90 days prior to study screening
8. A critically ill patient for whom transfer to an intensive care unit is scheduled, or patient who may likely have critical clinical deterioration within 48 hours;
9. Patients with serious, uncontrolled disease, including but not limited to neutropenia expected to last >7 days (Investigator discretion) or with an estimated life expectancy shorter than 6 months
10. Patients diagnosed with any cancer requiring taxane-based chemotherapy
11. Patients with digestive stoma, known conditions at risk for intestinal obstruction, or known achlorhydria
12. Contra-indication to oral therapy (eg, severe nausea/vomiting or ileus) or patient having tube feeding
13. Patients unable or expected to be unable within 48 hours to receive a medication by oral route administration
14. Known hypersensitivity to the activated charcoal, or to any of the constituents or excipients of DAV132
15. Patients taking any drug/medication acting on (eg, metronidazole; sulfasalazine) or absorbed in the colon.
16. Female patients planning a pregnancy, pregnant or breastfeeding
17. Patients already included into this study
18. Patients in an exclusion period of a previous study
19. Patients with any social or logistical condition which in the opinion of the Investigator, may interfere with the conduct of the study, such as incapacity to understand well, not willing to collaborate, or cannot easily be contacted after discharge
20. Patients not covered by a health insurance system where applicable and in compliance with the recommendations of the national laws in force relating to biomedical research.
21. Patients under administrative or legal supervision.