Clostridium Difficile (C. Difficile)Phase 2NCT03988855
An Exploratory, Open-Label, Oligo-Center Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Intravenous DNV3837 in Subjects With Clostridium Difficile Infection
A Phase 2 study testing DNV3837 in people with Clostridium Difficile (C. Difficile), run by Deinove at 13 sites in 2 countries.
Trial summary
This is an open-label study to evaluate the safety, efficacy, and PK of DNV3837 at a dose of 1.5 mg/kg actual body weight(BW)/day administered via IV infusion in subjects with CDI. The study will be conducted in 2 subsequent parts. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile (C. Difficile)
- What is being tested?
- DNV3837
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 2 Aug 2019to Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria to be enrolled in the study:
- The subject or a legally authorized representative must sign informed consent;
- The subject must be 18 years of age;
- Subjects must have a diagnosis of CDI defined as follows:
- Diarrhea, defined as a change in bowel habits, with > 3 liquid stools or unformed bowel movements (UBMs) [Bristol Stool Scale 6 or 7] or > 200 mL unformed stool for subjects having rectal collection devices in the 24 hours prior to start of study drug; AND
- The subject has the following positive tests on a stool sample produced within 72 hours prior to the start of study drug as determined by:
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- A positive C. difficile glutamate dehydrogenase (GDH) test by a Food and Drug Administration (FDA)-cleared enzyme immunoassay (EIA); AND
- A positive toxin test (presence of either C. difficile Toxin A [TcdA] and/or C. difficile Toxin B [TcdB]) by an FDA-cleared EIA; OR
- A positive toxin gene test (presence of either C. difficile Toxin A gene [tcdA] and/or C. difficile Toxin B gene [tcdB]) by an FDA-cleared nucleic acid amplification test; OR
- A positive cell cytotoxicity neutralization assay; OR
- positive toxigenic culture;
- Subjects with a first episode or recurrence of CDI with at least 1 of the following criteria:
- Current diagnosis of non-severe CDI must have a white blood cell (WBC) count ≤15,000 cells/µL (15 × 10^9 cells/L) and serum creatinine <1.5 mg/dL;
- Subjects with a current diagnosis of severe CDI must have any of the following criteria:
- WBC count >15,000 cells/µL (15 x 10^9 cells/L);
- Serum creatinine ≥ 1.5 mg/dL;
- Colitis on computed tomography or magnetic resonance imaging scan or ultrasound; OR
- Severe abdominal pain, vomiting, ileus, temperature >38.9°C, or albumin level <2.5 g/dL in which CDI is strongly suspected and other non-CDI causes of infection have been ruled out;
- Is currently failing antibiotic therapy for CDI, as defined by ongoing or worsening signs and symptoms and testing as per Inclusion Criterion 3 above, after at least 72 hours of therapy;
- The subject meets Inclusion Criteria 4a or 4b and has received no more than 24 hours of prior antimicrobial treatment for the current episode of CDI with oral/rectal vancomycin, IV/oral metronidazole, or oral fidaxomicin prior to Screening;
- Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or post-menopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone in the post-menopausal range at Screening, based on the central laboratory's ranges;
- Women of childbearing potential (ie, not post-menopausal or surgically sterilized) must have a negative urine and serum pregnancy test result before randomization. Participating women of childbearing potential must agree to use 1 highly effective method of contraception AND an acceptable barrier method (condom plus spermicide) OR 2 highly effective methods of contraception throughout the duration of the study and for 30 days following the last study drug administration. Highly effective methods of contraception that result in a low failure rate (ie, <1% per year) when used consistently and correctly include the following:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, or intrauterine hormone-releasing system for at least 12 weeks before Screening;
- Bilateral tubal occlusion or vasectomized partner at least 26 weeks before Screening;
- Sexual abstinence; NOTE: True abstinence, when in line with the preferred and usual lifestyle of the subject, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug treatment. Periodic abstinence (eg, calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception;
- Male subjects must agree to abstain from sperm donation and use condoms with spermicide during sexual intercourse between Screening and at least 90 days after administration of the last dose of study drug. Male subjects must ensure non pregnant female partners of childbearing potential comply with the contraception requirements in Inclusion Criterion 8.
Who cannot join
- Subjects will not be enrolled in the study if they meet any of the following exclusion criteria:
- The subject is likely to require surgical intervention (eg, subjects with fulminant CDI who fail to respond and progress to systemic toxicity, peritonitis, or toxic colonic dilatation and bowel perforation) and/or be switched to an already approved treatment regimen in the coming 48 hours due to a rapidly degrading condition;
- The subject displays evidence of acute renal impairment with a creatinine clearance of <50 mL/min as measured by the Cockcroft Gault formula;
- The subject is receiving hemodialysis or continuous venous hemofiltration;
- The subject has ALT or AST serum levels >1.5 × ULN, and total bilirubin serum concentration > ULN per the testing laboratory;
- The subject displays evidence of chronic hepatic impairment (Child-Pugh class B or C);
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- The subject is pregnant or breastfeeding;
- The subject requires the ongoing use of anti-motility agents (eg, anti-diarrheals, anti peristaltics) or laxatives, unless approved by the Medical Monitor. Chronic and continued use of such products may be permitted during the study if bowel motility has stabilized;
- The subject requires the ongoing use of concomitant antibiotics to treat CDI (other than study drug) (eg, oral/rectal vancomycin, IV/oral metronidazole, oral fidaxomicin) or IV immunoglobulin;
- The subject requires the ongoing use of medications that are substrates and/or inhibitors of P glycoprotein (P-gp) or breast cancer resistance protein (BCRP). Subjects who are on such medications can be enrolled in the study if that medication can be safely stopped or replaced by another appropriate medication for the duration of the Treatment Period. Use of medications that are known P gp/BCRP substrates and/or inhibitors is permitted after completion of the Treatment Period
- The subject has a known hypersensitivity or intolerance to DNV3837 or sorbitol;
- The subject has a history of active hepatitis B virus or hepatitis C virus that requires ongoing therapy, or human immunodeficiency virus with the most current cluster of differentiation 4 (CD4+) <200 copies/mL;
- The subject has participated in other clinical research studies using an investigational antibacterial or non antibacterial agent within 1 month prior to Screening;
- The subject is unable or unwilling, in the judgment of the Investigator, to comply with the protocol; or
- The subject is an employee of the Investigator, study site, Sponsor, or contract research organization with direct involvement in the proposed study or other studies under the direction of the Investigator, study site, or Sponsor, or a family member of the site employee or the Investigator.
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States10 sites, 4 recruiting
- Withdrawn
Pinnacle Research Group
Anniston, Alabama, 36207
- Recruiting
Mercury Street Medical
Butte, Montana, 59701
John Pullman, 406-723-1375, john.pullman@mercurystmed.com
- Withdrawn
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Snake River Research, PLLC
Idaho Falls, Idaho, 83404
Richard Nathan, 208-535-8404, rnathan@snakerr.com
- Withdrawn
DiGiovanna Institute for Medical Education and Research
North Massapequa, New York, 11758
- Withdrawn
Temple University Hospital
Philadelphia, Pennsylvania, 19140
- Recruiting
University of California (UC) Davis Medical Center
Sacramento, California, 95817
Cohen Stuart, MD, 916-734-5176, stcohen@ucdavis.edu
- Withdrawn
University of Utah
Salt Lake City, Utah, 84112
- Recruiting
Southern Star Research Institute, LLC.
San Antonio, Texas, 78229
Jeff Bullock, 210-271-0606, js_bull@yahoo.com
- Withdrawn
Infectious Disease Consultants (IDC) Clinical Research
Wichita, Kansas, 67214
Canada3 sites, 3 recruiting
- Not yet recruiting
University of Calgary
Calgary, Alberta, T2N 4N1
Thomas Louie, Thomas.Louie@albertahealthservices.ca
- Recruiting
The Medical Arts Health Research Group - Kelowna
Kelowna, British Columbia, BC V1Y 4N7
Issa Ephtimios, drephtimios@medicalartsresearch.ca
- Recruiting
Health Sciences Center, Eastern Health
Saint Johns, Newfoundland and Labrador, A1B 3V6
Peter Daley, pkd336@mun.ca
About this study
This is an open-label study to evaluate the safety, efficacy, and PK of DNV3837 at a dose of 1.5 mg/kg actual body weight(BW)/day administered via IV infusion in subjects with CDI. The study will be conducted in 2 subsequent parts.
In Part 1 of the study, 10 subjects of either sex with severe or non-severe CDI will be enrolled to receive DNV3837.
Read more
In Part 2 of the study, up to 30 subjects with severe or non-severe CDI will be enrolled to receive DNV3837.
In both parts of the study, treatment infusions will be administered at a constant rate resulting in a total IV infusion duration of 6 hours per day, for a total maximum daily dose of 120 mg DNV3837. Infusions will be administered once daily for 10 consecutive days. The objectives of the study are:
- To evaluate the safety of intravenous (IV) DNV3837;
- To evaluate the efficacy of IV DNV3837;
- To assess the pharmacokinetics (PK) of DNV3837 and DNV3681 in plasma and of DNV3681 in urine and feces;
- To assess C. difficile using microbiological assessments;
- To assess the proportion of subjects colonized with vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase (ESBL) organisms, or carbapenem-resistant Enterobacteriaceae (CRE) in feces; and
- To assess changes in the fecal microbiome using 16S ribosomal ribonucleic acid (RNA) analysis
- Conditions
- Clostridium Difficile (C. Difficile)
- Being tested
- DNV3837
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNV3837Drug
Treatment infusions will be administered at a constant rate resulting in a total IV infusion duration of 6 hours per day, for a total maximum daily dose of 120 mg DNV3837. Infusions will be administered once daily for 10 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | 10 subjects of either sex with severe or non-severe CDI will be enrolled to receive DNV3837. Treatment infusions will be administered at a constant rate resulting in a total IV infusion duration of 6 hours per day, for a total daily dose of 1.5 mg/kg actual body weight(BW)/day DNV3837. Infusions will be administered once daily for 10 consecutive days. Receives: Drug: DNV3837 |
| Part 2 | Experimental | 30 subjects with severe or non-severe CDI will be enrolled to receive DNV3837. Treatment infusions will be administered at a constant rate resulting in a total IV infusion duration of 6 hours per day, for a total daily dose of 1.5 mg/kg actual body weight(BW)/day DNV3837. Infusions will be administered once daily for 10 consecutive days Receives: Drug: DNV3837 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to resolution of diarrhea
Measured: Day 12
Treatment Success at Test of Cure
No relapse - Relapse is defined as a new episode of diarrhea (>3 liquid stools or UBMs [Bristol Stool Scale 6 or 7]) that results in the subject receiving antimicrobial treatment active against C. difficile. Confirmed relapse is further defined as a new episode of diarrhea (>3 liquid stools or UBMs [Bristol Stool Scale 6 or 7]) with a positive C. difficile free toxin test and the requirement of antimicrobial treatment active against C. difficile;
- Alive;
- No additional antimicrobial or anti-diarrheal therapies for CDI
Measured: 12 days
All-Cause Mortality
Measured: Day 30
Clostridium difficile Infection attributable mortality
Measured: Day 30
Incidence of relapse at Test of Cure
Measured: 12 days
Treatment failure at Test of Cure
Measured: 12 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2019
- Study start2 Aug 2019
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clostridium Difficile (C. Difficile)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Deinove
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03988855
- Sponsor's protocol ID
- 001C16
- Status last verified
- Sep 2022
- First submitted
- 12 Jun 2019
- Last updated
- 7 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory, Open-Label, Oligo-Center Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Intravenous DNV3837 in Subjects With Clostridium Difficile Infection
- ClinicalTrials.gov ID
- NCT03988855
- Acronym / sponsor ID
- 001C16
- Conditions
- Clostridium Difficile (C. Difficile)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- DeinoveIndustry (pharma, biotech, devices)
- Study start
- 2 Aug 2019 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 18 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label study to evaluate the safety, efficacy, and PK of DNV3837 at a dose of 1.5 mg/kg actual body weight(BW)/day administered via IV infusion in subjects with CDI. The study will be conducted in 2 subsequent parts.
In Part 1 of the study, 10 subjects of either sex with severe or non-severe CDI will be enrolled to receive DNV3837.
In Part 2 of the study, up to 30 subjects with severe or non-severe CDI will be enrolled to receive DNV3837.
In both parts of the study, treatment infusions will be administered at a constant rate resulting in a total IV infusion duration of 6 hours per day, for a total maximum daily dose of 120 mg DNV3837. Infusions will be administered once daily for 10 consecutive days. The objectives of the study are:
- To evaluate the safety of intravenous (IV) DNV3837;
- To evaluate the efficacy of IV DNV3837;
- To assess the pharmacokinetics (PK) of DNV3837 and DNV3681 in plasma and of DNV3681 in urine and feces;
- To assess C. difficile using microbiological assessments;
- To assess the proportion of subjects colonized with vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase (ESBL) organisms, or carbapenem-resistant Enterobacteriaceae (CRE) in feces; and
- To assess changes in the fecal microbiome using 16S ribosomal ribonucleic acid (RNA) analysis
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: DNV383710 subjects of either sex with severe or non-severe CDI will be enrolled to receive DNV3837. Treatment infusions will be administered at a constant rate resulting in a total IV infusion duration of 6 hours per day, for a total daily dose of 1.5 mg/kg actual body weight(BW)/day DNV3837. Infusions will be administered once daily for 10 consecutive days. |
| Part 2 | Experimental | Drug: DNV383730 subjects with severe or non-severe CDI will be enrolled to receive DNV3837. Treatment infusions will be administered at a constant rate resulting in a total IV infusion duration of 6 hours per day, for a total daily dose of 1.5 mg/kg actual body weight(BW)/day DNV3837. Infusions will be administered once daily for 10 consecutive days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- The subject or a legally authorized representative must sign informed consent;
- The subject must be 18 years of age;
- Subjects must have a diagnosis of CDI defined as follows:
- Subjects with a first episode or recurrence of CDI with at least 1 of the following criteria:
- The subject meets Inclusion Criteria 4a or 4b and has received no more than 24 hours of prior antimicrobial treatment for the current episode of CDI with oral/rectal vancomycin, IV/oral metronidazole, or oral fidaxomicin prior to Screening;
Key exclusion criteria (15 listed)
- Subjects will not be enrolled in the study if they meet any of the following exclusion criteria:
- The subject is likely to require surgical intervention (eg, subjects with fulminant CDI who fail to respond and progress to systemic toxicity, peritonitis, or toxic colonic dilatation and bowel perforation) and/or be switched to an already approved treatment regimen in the coming 48 hours due to a rapidly degrading condition;
- The subject displays evidence of acute renal impairment with a creatinine clearance of <50 mL/min as measured by the Cockcroft Gault formula;
- The subject is receiving hemodialysis or continuous venous hemofiltration;
- The subject has ALT or AST serum levels >1.5 × ULN, and total bilirubin serum concentration > ULN per the testing laboratory;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DNV3837Treatment infusions will be administered at a constant rate resulting in a total IV infusion duration of 6 hours per day, for a total maximum daily dose of 120 mg DNV3837. Infusions will be administered once daily for 10 consecutive days. | Drug | Part 1, Part 2 |
Primary outcome
Time to resolution of diarrhea
Time frame: Day 12
Treatment Success at Test of Cure
Time frame: 12 days
No relapse - Relapse is defined as a new episode of diarrhea (>3 liquid stools or UBMs [Bristol Stool Scale 6 or 7]) that results in the subject receiving antimicrobial treatment active against C. difficile. Confirmed relapse is further defined as a new episode of diarrhea (>3 liquid stools or UBMs [Bristol Stool Scale 6 or 7]) with a positive C. difficile free toxin test and the requirement of antimicrobial treatment active against C. difficile; * Alive; * No additional antimicrobial or anti-diarrheal therapies for CDI
All-Cause Mortality
Time frame: Day 30
Clostridium difficile Infection attributable mortality
Time frame: Day 30
Incidence of relapse at Test of Cure
Time frame: 12 days
Treatment failure at Test of Cure
Time frame: 12 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DNV3837 in people with Clostridium Difficile (C. Difficile), run by Deinove at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Georges Gaudriault (+33 4 48 19 01 24, georges.gaudriault@deinove.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to resolution of diarrhea (time frame: Day 12). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2022.