Assessing Infectious Threats in “Healthy” FMT Donors: Results of an Assessment Program to Support a Next-Generation Drug for Recurrent Clostridium difficile Infection

Courtney Jones, BS; Mary Kay Sobcinski, RN, MHA; Matt Adams MS; Rebiotix Inc, Roseville, MN

Background

• Microbiota Restoration Therapy is the Rebiotix platform for delivering human-derived microbes into a sick patient’s intestinal tract to treat disease.
• RBX2660 (microbiota suspension) is currently under investigation for recurrent Clostridium difficile infection (CDI).
• RBX2660 is sourced from human-derived microbes and manufactured using standardized, quality controlled processes.
• A donor program was implemented to provide a reliable source of raw material to supply Phase 2 studies.

Donor Recruitment and Screening

• Potential donors were recruited by word-of-mouth.
• Nearby universities were targeted as a source of young, healthy donors.
• A one-time recruitment bonus and nominal payments for accepted donations were offered.
• Potential donors underwent an initial screening process (Figure 1) for an extensive list of blood and stool pathogens prior to enrollment.
• Failures were permanently excluded.

Ongoing Donations

• If accepted into the program, donors agreed to make a minimum of 3 donations per week. A maximum of 10 donations per week was allowed (2 times daily, Monday through Friday). Each donation was tested for blood and stool pathogens.
• Daily health and diet questionnaires were completed with each donation to ensure there were no major changes in travel, medication, diet and health status (Figure 2).
• All donations were made on site and stored under controlled conditions.
• Donations were not pooled; aliquots from every donated stool were tested for pathogens using an extensive screen.
• At the end of each approximately 45-day donation cycle (Figure 3), donors underwent blood testing and donated aliquots underwent testing for pathogens.
• A positive result on any of the screens triggered destruction of all drug product associated with the donor during a cycle and exclusion of the donor from the program.

Conclusions

• A substantial number of outwardly healthy donors used to source intestinal microbes for a drug under study for recurrent Clostridium difficile infection were found unsuitable due to underlying conditions.
• Reasons for rejection included asymptomatic carriage of an E. coli strain associated with hemorrhagic diarrhea and asymptomatic norovirus and rotavirus, which typically cause symptoms.
• Stringent screening of donors is required when sourcing live human-microbes used for treatment of disease.