An Exploratory, Open-Label, Oligo-Center Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Intravenous DNV3837 in Subjects With Clostridium Difficile Infection

Inclusion Criteria

• •1. The subject or a legally authorized representative must sign informed consent;
• •2. The subject must be 18 years of age;
• •3. Subjects must have a diagnosis of CDI defined as follows:
• •1. 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
• •2. 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:
• •* 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;
• •4. Subjects with a first episode or recurrence of CDI with at least 1 of the following criteria:
• •1. 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;
• •2. 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;
• •3. 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;
• •6. 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;
• •7. 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:
• •1. 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;
• •2. Bilateral tubal occlusion or vasectomized partner at least 26 weeks before Screening;
• •3. 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;
• •8. 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.