Does the Donor Matter? Results from PUNCH CD 2: A Randomized Controlled Trial of a Microbiota-based Drug for Recurrent Clostridium difficile Infection

Abstract

Introduction: Questions about applicability of a universal donor vs. donor-to-patient matching have been raised in regards to microbiota-based therapies for recurrent Clostridium difficile Infection (CDI). We report on donor-to-patient outcomes in the PUNCH CD 2 trial, a randomized, placebo-controlled study of RBX2660. Methods: Patients in the blinded phase of the PUNCH CD 2 trial were randomized to receive either: 2 doses of RBX2660; 2 doses of placebo; or 1 dose of RBX2660 and 1 dose of placebo via enema with doses 7 days apart. RBX2660 is a microbiota-based drug manufactured from human-derived microbes using standardized processes in donor-specific batches that can be tracked to individual patients and outcomes; donors were randomized to patients for each dose. A generalized linear mixed effects model with binomial distribution was used to evaluate outcomes. Both the donors and patients were treated as random effects. Results: A total of 83 patients (mean age 62 years; 59% female) who received at least 1 dose of RBX2660 were included in the analysis. The donor was not significant (P > 0.99) for predicting responses (Table 1). The variance = 0 indicating that no difference in outcome by donor was expected and that the treatment rates for success and failure were the same for each donor.Table 1: Outcomes for Donors and PatientsConclusion: This analysis of the PUNCH CD 2 study demonstrates that the donor does not matter with regard to the efficacy of RBX2660 administration for recurrent CDI. The results are consistent with a previously reported analysis of the PUNCH CD study, a prospective open-label study of RBX2660.1 Thus, the data from two clinical studies demonstrate that RBX2660 prepared from a universal donor pool is appropriate without donor-to- patient matching. However, this may not be the case for indications other than CDI.