The QBECO-CD-02 trial in subjects with moderate to severe Crohn's disease (CD) is intended to build on past experience with QBECO SSI and further establish the safety and efficacy of QBECO SSI for the induction of clinical and/or endoscopic response and remission.~i. Overall Design:~Phase II, randomized, double-blind, placebo-controlled study in subjects with moderate to severe Crohn's disease to establish the safety and efficacy of QBECO SSI for the induction and maintenance of clinical and/or endoscopic response and remission. The study will be conducted in three stages; a Lead-in, Main Induction and Main Maintenance . The first 20 patients will be enrolled in the Lead-in study, at selected study centers. Subsequent patients will be enrolled in the Main study. The Lead-in component will be an open-label study to evaluate endoscopic healing endpoints. The Main Induction study will be randomized and placebo-controlled. Participants meeting response criteria following the Main Induction study will be eligible to continue into the Main Maintenance study, remaining on their initially randomized treatment. Participants not meeting response criteria will complete their follow-up and study involvement at the end of the Main Induction.~Primary Endpoints will be evaluated at various times throughout each stage of the study. In the Lead-In study, primary endpoints will be measured at Week 16 and 26 for determination of the induction duration and again at Week 52 as initial data on maintenance. In the Main Induction, the primary endpoints will be assessed when the last subject completes the induction period, either Week 16 or Week 26 depending on the finding of the Lead-In. In the Main Maintenance, the primary endpoints will be measured at Week 52. Safety Assessments will be carried out throughout the study and at the Week 56 visits for all subjects completing the study.~The study will be run at approximately 50 study centers in Canada, the United States of America and Eastern Europe.~ii. Number of Participants:~20 participants will be enrolled in the Lead-In study. No Lead-In study participants will be enrolled in the Main Induction or Maintenance component of the study.~150 participants will be randomized to the Main Induction study, resulting in an estimated total of 70 subjects proceeding to the Main Maintenance component of the study.~iii. Intervention Groups and Duration:~Approximately 170 adult subjects (N=170) with moderate to severe CD, 20 patients in the Lead-In study and 150 patients in the Main study, stratified by prior anti-TNFα inhibitor/ biologic therapy use. Patients will be randomized 2:1, active drug:placebo, and will receive 52 weeks of QBECO SSI treatment or placebo.~iv. Objectives and Endpoints:~Lead-In:~Primary~To determine whether Week 26 provides superior endoscopic healing outcomes compared to Week 16~To evaluate the incidence of adverse events (safety & tolerability) as measured by frequency and severity of adverse events.~Secondary~To determine the effect of QBECO SSI on endoscopic remission at the end of 52 weeks of treatment~To determine the effect of QBECO SSI on clinical remission, as measured by abdominal pain and soft-stool frequency, at the end of the induction period~Main:~Induction:~Primary~To determine the effect of QBECO SSI on clinical remission, as measured by abdominal pain and soft-stool frequency, at the end of the induction period~To determine the effect of QBECO SSI on endoscopic remission at the end of the induction period~To evaluate the incidence of adverse events (safety and tolerability) as measured by frequency and severity of adverse events.~Secondary~To determine the effect of QBECO SSI on abdominal pain score at the end of the induction period (i.e., change from baseline)~To determine the effect of QBECO SSI on soft-stool score at the end of the induction period (i.e., change from baseline)~To determine the effect of QBECO SSI on endoscopic response at the end of the induction period~To determine the effect of QBECO SSI on Simple Endoscopic Score for Crohn's Disease (SES-CD) scores at the end of the induction period as defined by SES-CD reduction by ≥25% and ≥75% and change from baseline~To determine the effect of QBECO SSI on histological activity at the end of induction period as defined by 25%, 50% and 75% reduction in global colonic Global Histologic Disease Activity Score (GHAS) and Robarts Histological Index (RHI)~To determine the effect of QBECO SSI on simultaneous clinical and endoscopic remission at the end of the induction period~Maintenance:~Primary~To determine the effect of QBECO SSI on clinical remission, as measured by abdominal pain and soft-stool frequency, at the end of the maintenance period~To determine the effect of QBECO SSI on endoscopic remission at the end of the maintenance period~To determine the safety and tolerability of QBECO SSI treatment, as measured by safety laboratory assessments, vital signs, frequency and severity of adverse events and physical examinations.~Secondary~To determine the effect of QBECO SSI on clinical remission and endoscopic remission among subjects who were in clinical or endoscopic remission at the end of induction.~To determine the effect of QBECO SSI on abdominal pain score at the end of maintenance period (i.e., change from baseline)~To determine the effect of QBECO SSI on soft-stool score at the end of maintenance period (i.e., change from baseline)To determine the effect of QBECO SSI on endoscopic response at the end of the maintenance period~To determine the effect of QBECO SSI on SES-CD scores at the end of the maintenance period as defined by SES-CD reduction by ≥25% and ≥75% and change from BL~To determine the effect of QBECO SSI on histological activity of CD patients at the end of the maintenance period as defined by 25%, 50% and 75% reduction in global colonic GHAS and RHI~To determine the effect of QBECO SSI on simultaneous clinical and endoscopic remission at the end of the maintenance period
The QBECO-CD-02 trial in subjects with moderate to severe Crohn's disease (CD) is intended to build on past experience with QBECO SSI and further establish the safety and efficacy of QBECO SSI for the induction of clinical and/or endoscopic response and remission.~The study will be conducted in three stages; a Lead-in, Main Induction and Main Maintenance .The first 20 patients will be enrolled in the Lead-in study, at approximately 5 study centers in Canada. Subsequent patients will be enrolled in the Main study, which aims to enroll 150 patients. The Lead-in component will be an open-label study to evaluate endoscopic healing endpoints. The Main Induction study will be randomized and placebo-controlled. Participants meeting response criteria following the Main Induction study will be eligible to continue into the Main Maintenance study, remaining on their initially randomized treatment. Participants not meeting response criteria will complete their follow-up and study involvement at the end of the Main Induction.