The Efficacy of Denosumab in Active Crohn's Disease
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|ClinicalTrials.gov Identifier: NCT02321280|
Recruitment Status : Completed
First Posted : December 22, 2014
Last Update Posted : October 15, 2018
Denosumab, a fully human monoclonal antibody to RANKL was approved for the treatment of postmenopausal osteoporosis in June 2010. It is administered subcutaneously once every 6 months and is highly effective in reducing the risk of vertebral, non-vertebral, and hip fracture risk. There are 3 main concepts underpinning the rationale for using Denosumab to treat CD.
- CD is associated with an increased risk for osteoporosis and the biology of osteoporosis and T cell mediated inflammation, thought to be integral in CD, involve the RANKL paradigm
- Animal models of bone loss and colitis treated with RANKL inhibitors improve both bone mass and colitis. A dinitrofluorobenzene sulfonic acid (DNBS) model of colitis in our lab showed significant improvement with Denosumab treatment compared to vehicle (saline) treatment.
- CD is associated with an increase in mutations at the locus that encodes for RANKL The investigators are conducting an open label pilot study of single dose Denosumab 120 mg s.c. to patients with active Crohn's disease, with assessment of clinical response and remission at 12 weeks.
|Condition or disease||Intervention/treatment||Phase|
|Crohn Disease||Drug: Denosumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Denosumab (A Monoclonal Antibody to Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL) in Crohn's Disease|
|Study Start Date :||February 2015|
|Actual Primary Completion Date :||April 20, 2018|
|Actual Study Completion Date :||April 20, 2018|
Experimental: Single arm single dose of denosumab
Open label = Single dose administration of single dose Denosumab 120 mg subcutaneously
Single dose subcutaneous administration
- Disease Response [ Time Frame: week 12 ]A drop in CDAI of 100 points
- Disease Remission [ Time Frame: week 12 ]Decrease in CDAI to ≤150 points at 12 weeks.
- fecal calprotectin decrease [ Time Frame: week 12 ]In those with elevated fecal calprotectin at baseline, reduction in fecal calprotectin to <250 ug/g at week 12.
- CRP decrease [ Time Frame: week 12 ]for those with increased CRP at baseline change in CRP to normal at week 12
- Endoscopy score decrease [ Time Frame: week 12 ]For those who underwent endoscopy within 1 month of study enrollment as part of standard of care and who underwent a repeat endoscopy within 1 month of study completion as part of standard of care, improvement in endoscopy by Crohn's Disease Endoscopy Inflammation Score (CDEIS) between baseline and second endoscopy.
- MRI improvement [ Time Frame: week 12 ]For those who underwent abdominal MRI within 1 month of study enrollment as part of standard of care and who underwent a repeat abdominal MRI within 1 month of study completion as part of standard of care then improvement in MRI findings by central reader (Dr H Greenberg) between baseline and second abdominal MRI.
- Safety will be assessed for any unforeseen adverse events at each study visit [ Time Frame: week 12 ]Serum calcium will be assessed at 3 days post drug administration and every 4 weeks. There is a rare incidence of hypocalcemia with use of this drug. Osteonecrosis of the jaw will be assessed at every study visit. This drug is rarely associated with this outcome especially in cancer patients. Liver enzymes every 4 weeks will be assessed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02321280
|University of Manitoba|
|Winnipeg, Manitoba, Canada, R3A 1R9|
|Principal Investigator:||Charles N Bernstein, MD||University of Manitoba|