TY - JOUR
T1 - Results from a Randomized, Placebo-Controlled Clinical Trial of a RBX2660 - A Microbiota-Based Drug for the Prevention of Recurrent Clostridium difficile Infection
AU - Dubberke, Erik R.
AU - Lee, Christine H.
AU - Orenstein, Robert
AU - Khanna, Sahil
AU - Hecht, Gail
AU - Gerding, Dale N.
N1 - Funding Information:
Financial support. The work was supported by Rebiotix Inc., Roseville, Minnesota.
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/9/28
Y1 - 2018/9/28
N2 - Background Despite advancements, recurrent Clostridium difficile infections (CDI) remain an urgent public health threat with insufficient response rates to currently approved antibiotic therapies. Microbiota-based treatments appear effective, but rigorous clinical trials are required to optimize dosing strategies and substantiate long-term safety. Methods This randomized, double-blind, placebo-controlled phase 2B trial enrolled adults with 2 or more CDI recurrences to receive: 2 doses of RBX2660, a standardized microbiota-based drug (group A); 2doses of placebo (group B); or 1 dose of RBX2660 followed by 1 dose of placebo (group C). Efficacy was defined as prevention of recurrent CDI for 8 weeks following treatment. Participants who had a recurrence within 8 weeks were eligible to receive up to 2 open-label RBX2660 doses. The primary endpoint was efficacy for group A compared to group B. Secondary endpoints included the efficacy of group C compared to group B, combined efficacy in the blinded and open-label phases, and safety for 24 months. Results The efficacy for groups A, B, and C were 61%, 45%, and 67%, respectively. The primary endpoint was not met (P =.152). One RBX2660 dose (group C) was superior to placebo (group B; P =.048), and the overall efficacy (including open-label response) for RBX2660-treated participants was 88.8%. Adverse events did not differ significantly among treatment groups. Conclusions One, but not 2, doses of RBX2660 was superior to placebo in this randomized, placebo-controlled trial. These data provide important insights for a larger phase 3 trial and continued clinical development of RBX2660. Clinical Trials Registration NCT02299570.
AB - Background Despite advancements, recurrent Clostridium difficile infections (CDI) remain an urgent public health threat with insufficient response rates to currently approved antibiotic therapies. Microbiota-based treatments appear effective, but rigorous clinical trials are required to optimize dosing strategies and substantiate long-term safety. Methods This randomized, double-blind, placebo-controlled phase 2B trial enrolled adults with 2 or more CDI recurrences to receive: 2 doses of RBX2660, a standardized microbiota-based drug (group A); 2doses of placebo (group B); or 1 dose of RBX2660 followed by 1 dose of placebo (group C). Efficacy was defined as prevention of recurrent CDI for 8 weeks following treatment. Participants who had a recurrence within 8 weeks were eligible to receive up to 2 open-label RBX2660 doses. The primary endpoint was efficacy for group A compared to group B. Secondary endpoints included the efficacy of group C compared to group B, combined efficacy in the blinded and open-label phases, and safety for 24 months. Results The efficacy for groups A, B, and C were 61%, 45%, and 67%, respectively. The primary endpoint was not met (P =.152). One RBX2660 dose (group C) was superior to placebo (group B; P =.048), and the overall efficacy (including open-label response) for RBX2660-treated participants was 88.8%. Adverse events did not differ significantly among treatment groups. Conclusions One, but not 2, doses of RBX2660 was superior to placebo in this randomized, placebo-controlled trial. These data provide important insights for a larger phase 3 trial and continued clinical development of RBX2660. Clinical Trials Registration NCT02299570.
KW - Clostridium difficile infection
KW - clinical trial
KW - microbiota-based therapy
KW - placebo
KW - recurrence
UR - http://www.scopus.com/inward/record.url?scp=85050595363&partnerID=8YFLogxK
U2 - 10.1093/cid/ciy259
DO - 10.1093/cid/ciy259
M3 - Article
C2 - 29617739
AN - SCOPUS:85050595363
VL - 67
SP - 1198
EP - 1204
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 8
ER -