Microbiota Restoration Therapy is the Rebiotix platform for delivering human-derived microbes into a sick patient’s intestinal tract to treat disease.
RBX2660, a microbiota-based drug, 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 for Phase 2 studies.
Donor Recruiting 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.
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 stool pathogens. Each batch ofRBX2660 was manufactured from stool donated by a single donor. Donations from multiple donors were not pooled.
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.
A total of 75 potential donors were screened from July 15, 2013 through December 31, 2015.
Of these, 11 (14.7%) failed the initial screening protocols. An additional 8 potential donors (12.9%) were lost to follow-up prior to making a donation.
A total of 56 (74.6%) passed the screening protocols and made at least one donation.
On subsequent retesting, a further 36 donors (64.3%) of the remaining donor pool were excluded: 23 failed one or more of the blood and pathogen screens; 13 discontinued participation.
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.