Inclusion Criteria:

• Able and willing to provide written informed consent prior to initiation of study treatment or of any study-specific procedures.
• Subjects with a qualifying episode of CDI in at least one of the following categories:
  • ≥ 18 years of age with a second or greater occurrence of CDI within the last 6 months;
  • Subjects ≥ 65 years of age with or without prior episodes of CDI who exhibit one or more of the following risk factors for recurrence:
    • Have kidney dysfunction, defined as creatinine clearance of < 60 mL/min/1.73 m2 at the time of the current episode of CDI;
    • Have a history of regular use of proton pump inhibitors (PPI) within the past 2 months and will be continuing use of PPIs throughout the study;
    • Have a history of CDI at any time.
  • Subjects ≥ 75 years of age with no additional risk factors for recurrence.
• The current qualifying episode of rCDI must meet all of the following criteria:
  • New onset of ≥ 3 loose/unformed bowel movements (i.e., Types 5 to 7 on the Bristol stool scale) within 24 hours for 2 consecutive days or > 8 loose/unformed bowel movements within 24 hours;
  • CDI symptoms started within 30 days (inclusive) prior to the day of randomization;
  • Stool sample collected before (or no later than 72 hours after) initiation of SOC antibiotic therapy for laboratory confirmation of toxigenic C. Difficile.
    • NOTE: every effort must be made to collect the diagnostic sample before SOC antibiotic therapy or within 24 hours after antibiotic therapy initiation, whenever possible.
• Diarrhea considered unlikely to have another etiology.
• Prior to randomizing a patient to receive the first dose of the study medication, a subject should:
  • Receive and complete an Investigator’s choice SOC antibiotic regimen of a minimum of 10 days and up to 21 days of total duration.
    • NOTE: antibiotic tapering is not allowed.
  • Meet successful clinical response criteria defined as when the qualifying/current episode of CDI is under symptomatic control with < 3 loose/unformed bowel movements within 24 hours for at least 2 consecutive days;
  • Have a positive C. difficile stool assay by EIA for Toxin A and/or B performed at the local laboratory or a study specific assay performed at the central laboratory.
• Women of childbearing potential must agree to either use a highly effective acceptable form of birth control (e.g., established hormonal birth control plus a barrier method, double barrier method: intrauterine device plus condom or spermicidal gel plus condom) or remain celibate during the study period and up to 3 months after the last dose of study drug.
• Able to receive the first dose of study drug on the last planned day of administration of SOC antibiotics for a qualifying episode of CDI, or no later than 1 day after completion of antibiotic dosing.
• Able and willing to follow study procedures (e.g., ingest up to 10 size 0 capsules per day for 14 days, comply with study visits, provide stool samples, and record information/interact with study tools).
• Recovered from any complications of severe or fulminant CDI and clinically stable by the time of randomization.

Exclusion Criteria: 

• History of diarrhea (defined as 3 or more loose stools per day lasting for at least 4 weeks) that is not related to C. difficile infection within the 3 months prior to randomization.
• Known or suspected toxic megacolon and/or known small bowel ileus at the time of randomization.
• Contraindication to oral/enteral therapy (e.g., severe reflux, severe nausea/vomiting, or ileus).
• Presence of white blood cell (WBC) count > 15 × 10^9 cells/L, or body temperature > 38.5 °C at the time of randomization.
• Prior administration of genetically modified investigational live bacterial/fungal/bacteriophage/viral isolates for CDI-associated diarrhea (Exception: prior use of yogurt or other food products containing live bacterial cultures or over the counter probiotics is permitted).
• History of administration of fecally-derived investigational live biotherapeutic products, or fecally-derived live bacterial isolates for CDI-associated diarrhea including fecal microbiota transplantation (FMT) within the last 6 months.  Use of drugs that alter gut motility (e.g., loperamide, diphenoxylate, or opium tincture) within 3 days prior to the planned first dose of study drug.
• Planned administration of oral or parenteral antibacterial therapy for a non-CDI indication after randomization.
• History of acute leukemia or hematopoietic stem cell transplantation or myelosuppressive chemotherapy within 2 months prior to randomization.
• Subjects with compromised immune system, including: a. Absolute neutrophil count (ANC) of < 0.5 ×10^9 cells/L on 2 consecutive occasions within 7 days prior to randomization or sustained ANC < 1 × 10^9 cells/L;
• Corticosteroid use at daily doses higher than 20 mg of prednisone equivalent within 14 days prior to randomization, with the exception of inhaled or topical corticosteroids, which are permitted.
  • NOTE: subjects with well-controlled human immunodeficiency virus (HIV) infection and CD4 count > 300 cells/mcL may be enrolled, provided that all other protocol eligibility requirements are met.
• Current or immediate potential for mechanical ventilation or vasopressors for hemodynamic support.
• Life expectancy of < 3 months.
• Major gastrointestinal surgery (e.g., significant bowel resection or diversion) within 3 months prior to randomization or any history of total colectomy or bariatric surgery that disrupts the gastrointestinal lumen.
  • NOTE: appendectomy, cholecystectomy, or restrictive procedures, such as banding, may be permitted upon discussion with the Medical Monitor if at least 1 month since surgery has elapsed and upon the subject’s full recovery.
• Anticipated admission to an intensive care unit during or after the study drug administration treatment period.
  • NOTE: nursing homes, rehabilitation units, assisted living centers, and acute care hospitals are acceptable.
• Female subject who is pregnant or breastfeeding.
• Known hypersensitivity/allergy/intolerance to any ingredient in the VE303 study formulation (sucrose, histidine, yeast extract, cysteine, metabisulfite, and micro-crystalline cellulose).
• Clinically significant medical or surgical condition not mentioned in the above criteria that, in the Investigator’s opinion, could interfere with the administration of study drug, interpretation of study safety or efficacy data, or compromise the safety or wellbeing of the subject.
• History of confirmed celiac disease, inflammatory bowel disease, short gut, gastrointestinal tract fistulas, or ischemia.