SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02321280

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Denosumab (A Monoclonal Antibody to Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL) in Crohn's Disease

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. 1. 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 2. 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. 3. 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.

NCT02321280 Crohn Disease
MeSH: Crohn Disease
HPO: Crohn's disease

1 Interventions

Name: Denosumab

Description: Single dose subcutaneous administration

Type: Drug

Single arm single dose of denosumab


Primary Outcomes

Description: A drop in CDAI of 100 points

Measure: Disease Response

Time: week 12

Secondary Outcomes

Description: Decrease in CDAI to ≤150 points at 12 weeks.

Measure: Disease Remission

Time: week 12

Description: In those with elevated fecal calprotectin at baseline, reduction in fecal calprotectin to <250 ug/g at week 12.

Measure: fecal calprotectin decrease

Time: week 12

Description: for those with increased CRP at baseline change in CRP to normal at week 12

Measure: CRP decrease

Time: week 12

Description: 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.

Measure: Endoscopy score decrease

Time: week 12

Description: 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.

Measure: MRI improvement

Time: week 12

Description: 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.

Measure: Safety will be assessed for any unforeseen adverse events at each study visit

Time: week 12

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 rs2062305

5. Patients must carry at least one G allele at rs2062305.



HPO Nodes


HPO:
Crohn's disease
Genes 2
IGHM PSTPIP1