The Efficacy of Denosumab in Active Crohn's Disease

NCT02321280 | Completed Phase 1

• 1 other identifier: DIC 2014
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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. 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.

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (1)

• Disease Response

  A drop in CDAI of 100 points

  week 12

Secondary Outcomes (6)

• Disease Remission

  week 12

• fecal calprotectin decrease

  week 12

• CRP decrease

  week 12

• Endoscopy score decrease

  week 12

• MRI improvement

  week 12

Study Arms (1)

Single arm single dose of denosumab

EXPERIMENTAL

Open label = Single dose administration of single dose Denosumab 120 mg subcutaneously

Drug: Denosumab

Interventions

Denosumab DRUG

Single dose subcutaneous administration

Also known as: Xgeva, Prolia

Single arm single dose of denosumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent.
• Male or female subjects, 18 to 80 years of age, inclusive.
• Prior diagnosis of CD confirmed by endoscopy or imaging for \> 3 months prior to enrollment with active disease, defined as a Crohn's Disease Activity Index (CDAI) score \>220 to \<450 and at least one of either: fecal calprotectin \>250 ug/g feces, or CRP \>8 mg/L.
• Patients will have evidence of ileocolonic, colonic, or ileal disease that is visualized either endoscopically or on MRI within the prior 6 months.
• Patients must carry at least one G allele at rs2062305.
• Patients will be eligible for the study if they are receiving any of the following:
• mesalamine for \>8 weeks with the dose remaining stable for 4 weeks prior to screening;
• a maximum of 20 mg of prednisone per day (or steroid equivalent), with the dose remaining stable for 2 weeks prior to screening. Steroids must be held stable for the first 4 weeks of the study and then must be tapered by 5 mg per week, to be discontinued entirely by week 8;
• mercaptopurine, methotrexate or azathioprine for ≥3 months, with the dose remaining stable for 8 weeks prior to screening;

You may not qualify if:

• Monoclonal antibody or experimental agent use within 12 weeks before screening.
• Use of non-approved drugs for CD.
• Anticipated need for surgery within 12 weeks
• Active sepsis, or use of antibiotics within two weeks prior to screening for the treatment of infection.
• Pregnant, lactating or planning to become pregnant during the study
• Inability to reliably use birth control for men and women during the course of therapy.
• Known allergy to Denosumab or ingredients in formulation
• Treatment of cancer within the last 5 years (except for non-melanoma skin cancers).
• Recent jaw infection, invasive dental procedures (tooth extraction, dental implants or surgery), anti-angiogenic medications, or hypocalcemia within 1 month prior to screening.
• Patients will also be excluded if they meet any of the following criteria: Proctocolectomy or total colectomy; stoma; a history of allergy to murine proteins; or treatment with parenteral corticosteroids or corticotropin within four weeks before screening. Serum Hg \< 80 g/L, liver enzymes ≥ 2-fold elevated, or other serum biochemistry considered unsafe, or requiring treatment, in the opinion of the investigator.

Sponsors & Collaborators

• University of Manitoba: lead
• University of Toronto: collaborator
• McMaster University: collaborator

Study Sites (1)

University of Manitoba

Winnipeg, Manitoba, R3A 1R9, Canada

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Charles N Bernstein, MD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished Professor of Medicine

Study Record Dates

• First Submitted: December 11, 2014
• First Posted: December 22, 2014
• Study Start: February 1, 2015
• Primary Completion: April 20, 2018
• Study Completion: April 20, 2018
• Last Updated: October 15, 2018

Record last verified: 2018-10

Locations

CA (1)