Please indicate how many years of clinical research experience the Sub-Investigator has.

Please indicate how many years of research experience the Coordinator has.

(the address where study procedures such as consent will be conducted)

What percentage of prior studies conducted by the site met enrollment goals and timelines?

Indicate the number of studies that are currently being conducted at your site.

Provide details if you will utilize an EMR system, potential advertising, etc.

What is the anticipated number of patients to be enrolled per month?

How many of your patients have been diagnosed with CDI at your site in the last six months?

Please provide information on how you verify participant identity. (Identity will need to be verified before consent.)

Describe how CDI is diagnosed, confirmed, and treated at your site

Does your local laboratory confirm CDI by using one of the following tests (please indicate which ones are used by the lab);

•   enzyme immunoassay [EIA] for toxin A/B
• polymerase chain reaction [PCR]
• or toxigenic culture [TC] on a stool sample

Is your site able to collect stool samples from the participants to confirm CDI prior to SOC antibiotic treatment?

Inclusion criteria

For enrollment in Stage 1 (rCDI population):

• Age ≥ 12 years with a laboratory-confirmed qualifying episode of CDI and at least one prior occurrence of CDI within the last 6 months

For enrollment in Stage 2 (pCDI-hr population):

• Age ≥ 75 years with a laboratory-confirmed qualifying episode of CDI
• Laboratory-confirmed qualifying episode of CDI and at least two of the following risk factors:
• Age ≥ 65 years
• Kidney dysfunction, defined as estimated creatinine clearance 60mL/min/1.73 m2 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 (see Appendix 3)
• Has undergone solid organ or hematopoietic stem cell transplantation

For enrollment in either Stage 1 or Stage 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 at least 2 consecutive days
• CDI symptoms started within 4 weeks prior to the initiation of 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 EIA for toxin A/B and GDH, with PCR reflex testing for discordant GDH/EIA toxin results, as performed at either a local laboratory or the central laboratory
• Diarrhea considered unlikely to have another etiology

Prior to receiving study medication, the participant should:

• Receive and complete a course of SoC antibiotics for at least 10 days, up to a maximum of 21 days (Note: choice of SoC agent is at the physician’s discretion and antibiotic tapering is not allowed)
• Meet the criterion for a successful clinical response, defined as symptomatic control of the qualifying CDI episode, ie, < 3 loose/unformed bowel movements per 24 hours for at least 2 consecutive days
• Persons of childbearing potential must have a negative pregnancy test and must agree to either use a highly effective, acceptable form of birth control (eg, established hormonal birth control plus a barrier method, double barrier method [intrauterine device plus condom or spermicidal gel plus condom]), remain sexually abstinent during the study period and up to 3 months after the last dose of study drug, or be exclusively with female and/or vasectomized partner(s) who have had medical confirmation of surgical success
• 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 1 day after completion of antibiotic dosing
• Recovered from any complications of severe or fulminant CDI and be clinically stable by the time of randomization
• Able and willing to follow study assessments (eg, comply with study visits and procedures, provide blood and stool samples, complete questionnaires)
• Able and willing to provide written informed consent/assent prior to initiation of any study-specific procedure or study drug administration and aware of the potential risks and benefits of study enrollment and study drug administration.
• For participants younger than the age of majority (18 years of age in most geographies), the consent should be signed or co-signed by the participant’s legal guardian and a child-specific assent form may be used, consistent with local regulations and practices.

Exclusion Criteria:

• 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
• Laboratory-confirmed infectious diarrhea other than CDI (including bacterial, viral, or parasitic etiology) within 30 days prior to randomization
• Known or suspected toxic megacolon or small bowel ileus at the time of randomization
• History of confirmed celiac disease, inflammatory bowel disease, short gut, gastrointestinal (GI) tract fistulas, or ischemia
• Contraindication to oral/enteral therapy (eg, severe reflux, severe nausea/vomiting, or ileus) at the time of randomization
• White blood cell count > 15.0 × 109 cells/L at the time of randomization
• Absolute neutrophil count (ANC) of < 0.5 ×109 cells/L on 2 consecutive occasions within 7 days prior to randomization, or sustained ANC < 1.0 × 109 cells/L
• Use of probiotics within 2 weeks prior to randomization (Note: consumption of food-based probiotics such as yogurt, kombucha, and kefir is permissible)
• Receipt of bezlotoxumab during the course of SoC antibiotic treatment for the qualifying CDI episode
• Receipt of SER-109, RBX2660, or any other approved or investigational genetically modified live bacterial, fungal, viral, or bacteriophage isolates, fecal-derived live bacterial isolates, or other biotherapeutic products for CDI-associated diarrhea, including fecal microbiota transplantation, within 6 months prior to randomization
• Use of drugs that alter gut motility (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
• History of malignancy and receipt of chemotherapy or other treatments with known GI adverse effects within 2 months prior to randomization
• Receipt of any investigational drug or investigational vaccine within 30 days prior to randomization
• Current or immediate potential for mechanical ventilation or vasopressors for hemodynamic support
• Life expectancy of < 3 months
• Major GI surgery (eg, significant bowel resection or diversion) within 3 months prior to randomization, current ileostomy, or history of total colectomy.
• Participants with a history of appendectomy, cholecystectomy, or restrictive procedures, such as banding, may be permitted upon discussion with the Medical Monitor if surgery was at least 1 month prior to randomization and the participant has fully recovered
• Pregnant or breastfeeding
• Known hypersensitivity/allergy/intolerance to any ingredient in the VE303 study formulation (sucrose, histidine, yeast extract, cysteine, sodium metabisulfite, microcrystalline cellulose, simethicone, and magnesium stearate.)
• Clinically significant or poorly controlled 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’s safety or efficacy data, or compromise the safety or well-being of the participant.