VE303 for Prevention of Recurrent Clostridioides Difficile Infection

Key Inclusion Criteria (For enrollment in Stage 1: recurrent CDI population):

• Age ≥ 12 years where permitted, and ≥ 18 years in other locations, with a laboratory-confirmed qualifying episode of CDI and at least 1 prior occurrence within the last 6 months

Key Inclusion Criteria (For enrollment in Stage 2: primary CDI with high-risk for recurrence population):

• Age ≥ 75 years with a laboratory-confirmed qualifying episode of CDI
• OR age ≥ 12 years where permitted, and ≥ 18 years in other locations, with least two of the following risk factors:

• Age ≥ 65 years
• Kidney dysfunction, defined as estimated creatinine clearance < 60 mL/min/1.73 m^2 at the time of the qualifying CDI episode
• History of regular use of a proton pump inhibitor (PPI) within the past 2 months and expectation of continued use of PPIs throughout the study
• History of a prior CDI episode between 6 and 12 months prior to enrollment
• Immunosuppression due to an underlying disease or its treatment
• Has undergone solid organ or hematopoietic stem cell transplantation

Key Inclusion Criteria (For enrollment in Stage 1 or 2):

• The qualifying episode of CDI must meet all the following criteria:

• New onset of ≥ 3 unformed bowel movements (ie, Types 5 to 7 on the Bristol stool scale) within 24 hours for 2 consecutive days
• CDI symptoms started within 4 weeks prior to initiation of standard of care (SoC) antibiotic therapy for CDI
• Stool sample collected before (or no later than 72 hours after) initiation of SoC antibiotic therapy that was positive in a CDI laboratory test, defined as enzyme immunoassay (EIA) for toxin A/B and glutamate dehydrogenase (GDH) with polymerase chain reaction (PCR) reflex testing for discordant EIA/GDH results, performed at either a local laboratory or the central laboratory
• Diarrhea considered unlikely to have another etiology
• Prior to receiving any study medication, the participant should:

• Receive and complete a course of SoC antibiotic therapy for at least 10 days, up to a maximum of 28 days (Note: choice of agent is at the physician's discretion and antibiotic tapering is not allowed). It is permissible for decentralized participants to be randomized during SoC antibiotic administration.
• Meet the criterion of a successful clinical response, defined attaining symptomatic control of the qualifying CDI episode, ie, < 3 loose/unformed bowel movements per 24 hours for at least 2 consecutive days
• Able to receive the first dose of study drug on the last planned day of SoC antibiotic administration for a qualifying CDI episode, or no later than 2 days after completion of antibiotic dosing
• Recovered from any complications of severe or fulminant CDI and be clinically stable by the time of randomization

Key Exclusion Criteria (For both Stage 1 and Stage 2):

• History of chronic diarrhea (defined as ≥ 3 loose stools per day lasting for at least 4 weeks) within 3 months prior to randomization that is not related to CDI
• Known or suspected toxic megacolon or small bowel ileus at the time of randomization
• History of confirmed celiac disease, inflammatory bowel disease, microscopic colitis, short gut, GI tract fistulas, or a recent episode (within 6 months of screening) of intestinal ischemia or ischemic colitis
• Receipt of bezlotoxumab during the course of SoC antibiotic treatment for the qualifying CDI episode
• Use of antidiarrheal drugs (eg, loperamide, diphenoxylate) within 3 days prior to the planned first dose of study drug
• Anticipated administration of oral or parenteral antibacterial therapy for a non-CDI indication after randomization through Week 24 (end of study)
• Probiotics, whether characterized as a dietary/food supplement, or a drug, are prohibited within 2 days before starting study drug and through the dosing period. (Note: consumption of food-based products such as yogurt, kombucha, and kefir are permitted.)
• Absolute neutrophil count (ANC) of < 0.5 ×10^9 cells/L on 2 consecutive occasions within 7 days prior to randomization, or sustained ANC < 1.0 × 10^9 cells/L