Sutcliffe S¹, Kalyan S^1,2, Pankovich J¹, Chen JMH¹, Gluck R¹, Thompson D^3,4, Bosiljcic M¹, Bazett M¹, Fedorak RN⁵, Panaccione R⁶, Axler J⁷, Marshall JK⁸, Mullins DW⁹, Kabakchiev B¹⁰, McGovern DPB¹¹, Jang J¹, Coldman A¹², Vandermeirsch G¹, Bressler B¹³, Gunn H¹. Front Med (Lausanne). 2019 Jul 19;6:170. doi: 10.3389/fmed.2019.00170. eCollection 2019.

Author information

1 Qu Biologics Inc., Vancouver, BC, Canada.

2 Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

3 Emmes Canada, Burnaby, BC, Canada.

4 Department of Statistics and Actuarial Sciences, Simon Fraser University, Burnaby, BC, Canada.

5 Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.

6 Inflammatory Bowel Disease Unit, University of Calgary, Calgary, AB, Canada.

7 Toronto Digestive Disease Associates Inc., Vaughan, ON, Canada.

8 Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.

9 Department of Microbiology, Immunology and Medical Education, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.

10 Zane Cohen Centre for Digestive Diseases, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.

11 Cedars-Sinai Medical Center, Los Angeles, CA, United States.

12 Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada.

13 Gastrointestinal Research Institute, Vancouver, BC, Canada.

Abstract

Background: Current Crohn's disease (CD) therapies focus on suppressing immune function and come with consequent risk, such as infection and cancer. Notwithstanding, most CD patients still experience disease progression. There is a need for new CD treatment strategies that offer better health outcomes for patients. Aims: To assess safety, efficacy, and tolerability of a novel microbial-derived immunotherapy, QBECO, that aims to restore rather than suppress immune function in CD. Methods: A randomized, double-blind, placebo-controlled trial was conducted in 68 patients with moderate-to-severe CD. Primary endpoints: safety and Week 8 clinical improvement. Secondary endpoints: Week 8 clinical response and remission. Week 8 responders continued blinded treatment through Week 16; non-responders received open-label QBECO from Weeks 9-16. Exploratory analyses included immune biomarker and genotype assessments. Results: QBECO was well-tolerated. Mean reduction in Crohn's Disease Activity Index (CDAI) score was -68 for QBECO vs. -31 for placebo at Week 8. Improvement with QBECO continued through Week 16 (-130 CDAI reduction). Week 8 QBECO clinical response, improvement and remission rates were 41.2%, 32.4%, 29.4% vs. 26.5%, 23.5%, 23.5% for placebo. TNFα inhibitor-naïve subjects achieved higher response rates at Week 8 with QBECO (64%) vs. placebo (26%). Specific immune biomarkers were identified that linked to QBECO response. Conclusion: This proof-of-concept study supports further investigation for the use of QBECO as a novel immunotherapy approach for CD. Biomarker analyses suggests it may be feasible to personalize CD treatment with QBECO. Larger trials are now needed to confirm clinical improvement and the unique biological findings. Clinical Trial Number: NCT01809275(https://clinicaltrials.gov/ct2/show/NCT01809275).