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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03710694
Other study ID # DAV132-CL-2001
Secondary ID CIV-18-03-023465
Status Completed
Phase N/A
First received
Last updated
Start date October 31, 2018
Est. completion date August 9, 2019

Study information

Verified date August 2019
Source Da Volterra
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 260
Est. completion date August 9, 2019
Est. primary completion date August 9, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Intervention

Device:
DAV132
DAV132: Dosage: 15 g/day activated charcoal (22.5 g/day DAV132) Route: Oral Duration: duration of fluoroquinolone treatment + 2 days DAV132 is regulated as a medical device in Europe and as a drug in the United States of America.

Locations

Country Name City State
Bulgaria Multiprofile Hospital for Active Treatment Sveti Ivan Rilski - Kozloduy EOOD Internal Department Kozloduy
Bulgaria MHAT "Dr Nikola Vasilev " AD 1 Kyustendil
Bulgaria MHAT "Dr. Stamen Iliev" AD 4 Montana
Bulgaria Pernik EOOD Specialized Hospital for Active Treatment of Pulmonary Diseases - Phthisiatry Department Pernik
Bulgaria Hosp Ruse EOOD Ruse
Bulgaria Multiprofile Hospital for Active Treatment Silistra AD Department of pneumology and phtisiatry Silistra
Bulgaria Military Medical Academy, Clinic of Infectious Diseases Sofia
Bulgaria UMHATEM N.I.Pirogov Department of internal diseases Clinic of internal diseases Sofia
Bulgaria MHAT Sv. Anna Clinic of Urology Varna
Germany Universitaetsklinikum Frankfurt, Medizinische Klinik II Frankfurt am Main
Germany Universitaetsklinikum Jena Klinik für Innere Medizin IV Jena
Germany Universitätskliniken Köln (AöR) Klinik I für Innere Medizin Köln
Germany Medizinische Universitaetsklinik Abteilung Innere Medizin I Tuebingen
Romania Institutul de Pneumoftiziologie "MariusNasta" (Pavilionul IV), Sectia Pneumologie VII Bucuresti
Romania Institutului Clinic Fundeni, Sectia Clinica Urologie III Bucuresti
Romania Spitalul Clinic de Boli Infectioase si Tropicale Dr. Victor Babes, Sectia Pneumologie II Bucuresti
Romania Spitalului de Boli Infectioase si Tropicale "Dr. Victor Babes" Sectia Clinica de Boli Infectioase si Tropicale VI - adult Bucuresti
Romania Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca, Sectia Clinica Pneumologie I Cluj-Napoca
Romania The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca
Romania Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Victor Babes Craiova, Sectia Boli Infectioase Adulti II Craiova
Romania Spitalului Universitar de Urgenta Elias, Clinica Universitara de Geriatrie, Gerontologie si Psihogeriatrie, Sos. Bucuresti-Ploiesti Otopeni
Romania Spitalul Clinic de Boli Infectioase si Pneumoftiziologie "Dr. Victor Babes" Timisoara, Clinica II Pneumologie Timisoara
Romania Spitalului Clinic de Boli Infectioase si Pneumoftiziologie "Dr. Victor Babes", Sectia Pneumologie II Timisoara
Romania Spitalului Clinic Judetean de Urgenta "Pius Brînzeu" Timisoara, Sectia Clinica Urologie Timisoara
Serbia Clinical Hospital Centre Bezanijska Kosa Pulmonology Department Belgrad
Serbia General Hospital Department for Lung Diseases and Tuberculosis Cacak
Serbia Clinical Centre Kragujevac Clinic for Infectious Diseases Kragujevac
Serbia Clinical Centre of Nis Clinic for Lung Diseases Niš
Serbia Health Centre Uzice Department for Lung Diseases and Tuberculosis Užice

Sponsors (2)

Lead Sponsor Collaborator
Da Volterra Syneos Health

Countries where clinical trial is conducted

Bulgaria,  Germany,  Romania,  Serbia, 

References & Publications (4)

Burdet C, Sayah-Jeanne S, Nguyen TT, Hugon P, Sablier-Gallis F, Saint-Lu N, Corbel T, Ferreira S, Pulse M, Weiss W, Andremont A, Mentré F, de Gunzburg J. Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection. Antimicrob Agents Chemother. 2018 Sep 24;62(10). pii: e00925-18. doi: 10.1128/AAC.00925-18. Print 2018 Oct. — View Citation

Burdet C, Sayah-Jeanne S, Nguyen TT, Miossec C, Saint-Lu N, Pulse M, Weiss W, Andremont A, Mentré F, de Gunzburg J. Protection of Hamsters from Mortality by Reducing Fecal Moxifloxacin Concentration with DAV131A in a Model of Moxifloxacin-Induced Clostridium difficile Colitis. Antimicrob Agents Chemother. 2017 Sep 22;61(10). pii: e00543-17. doi: 10.1128/AAC.00543-17. Print 2017 Oct. — View Citation

de Gunzburg J, Ducher A, Modess C, Wegner D, Oswald S, Dressman J, Augustin V, Feger C, Andremont A, Weitschies W, Siegmund W. Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: A proof of concept study in healthy subjects. J Clin Pharmacol. 2015 Jan;55(1):10-6. doi: 10.1002/jcph.359. Epub 2014 Jul 16. — View Citation

de Gunzburg J, Ghozlane A, Ducher A, Le Chatelier E, Duval X, Ruppé E, Armand-Lefevre L, Sablier-Gallis F, Burdet C, Alavoine L, Chachaty E, Augustin V, Varastet M, Levenez F, Kennedy S, Pons N, Mentré F, Andremont A. Protection of the Human Gut Microbiome From Antibiotics. J Infect Dis. 2018 Jan 30;217(4):628-636. doi: 10.1093/infdis/jix604. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Safety endpoint: Proportion of patients having at least one adverse event (AE) related to DAV132 and/or to fluoroquinolones (FQs) and which relationship to product (DAV132 or FQ) is confirmed by the Independent Adjudication Committee (IAC). The IAC will review AEs according to the IAC charter, including Clostridium difficile infection (CDI) and antibiotic-associated diarrhea (AAD), in a blinded manner across both treatment groups, and confirm whether each AE is related or not to DAV132 and/or to the FQ received by the patient. 51 days after randomization
Secondary Safety endpoint: Number of AEs and proportion of patients with at least one AE 51 days after randomization
Secondary Efficacy/performance endpoint, clinical:Proportion of patients with CDI 51 days after randomization
Secondary Efficacy/performance endpoint, clinical: Proportion of patients with AAD 51 days after randomization
Secondary Efficacy/performance endpoint, clinical: Plasma levels of FQs Day 4
Secondary Efficacy/performance endpoint, biological: Level of free fecal concentrations of FQs Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator Day 1, Day 4, Day 6, 10 days after the end of FQs
Secondary Efficacy/performance endpoint, biological: Level of a-diversity of the intestinal microbiota Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator Day 1, Day 6, 10 days after the end of FQs, and 30 days after the end of FQs
Secondary Efficacy/performance endpoint, biological: Change from D1 of a-diversity of the intestinal microbiota Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator Day 6, 10 days after the end of FQs, and 30 days after the end of FQs
Secondary Efficacy/performance endpoint, biological: Levels of ß-diversity of the intestinal microbiota Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator Day 6, 10 days after the end of FQs, and 30 days after the end of FQs
Secondary Efficacy/performance endpoint, biological: Proportion of patients with resistant bacteria and/or yeasts in feces Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator Baseline and up to 10 days after the end of FQs
Secondary Efficacy/performance endpoint, biological: Proportion of patients with at least one occurrence of resistant bacteria and yeasts in feces (among patients negative at baseline) Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator up to 10 days after the end of FQs
Secondary Efficacy/performance endpoint, biological: Proportion of patients with acquisition of intestinal colonization by C. difficile (among patients negative at baseline) Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator up to 10 days after the end of FQs
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