RA Denosumab on Bone Microstructure Study

NCT01770106 | Completed Phase 4 DMC

• 1 other identifier: RA-2011.510
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to compare the effects of denosumab and a current standard treatment on cortical and trabecular microarchitecture at the radius and second metacarpal in rheumatoid arthritis (RA) patients with low bone mineral density using high resolution peripheral quantitative computed tomography (HR-pQCT) during a 6-month open-label randomized controlled study. Forty ambulatory Chinese females, who consent to receive alendronate as standard treatment subjective to the randomization, will be enrolled in this study. Subjects will be randomized to 2 arms receiving: 1) subcutaneous injection of denosumab 60mg (Prolia®) every 6 months (n=20), or 2) oral alendronate weekly (Fosamax® once weekly 70 mg, n=20). In addition, all patients will be given a daily calcium supplement (1500mg caltrate /day) and 1 multivitamin tablet per day. Efficacy and safety assessment will be performed at baseline, month 3 and month 6. aBMD of lumbar spine, total hip and non-dominant distal radius will be measured using dual-energy X-ray absorptiometry (DXA) and microarchitecture of bone is measured at the non-dominant distal radius and the second metacarpal bone of the non-dominant hand using HR-pQCT.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Bone density; Bone microarchitecture; HR-pQCT

Outcome Measures

Primary Outcomes (1)

• Changes from baseline in bone volumetric density at distal radius at 6th month

  Bone volumetric density is characterized by average volumetric bone mineral density (BMD) at distal radius by HR-pQCT

  Baseline to 6th month

Secondary Outcomes (13)

• Changes from baseline in trabecular bone microarchitecture at distal radius at 6th month

  Baseline to 6th month

• Changes from baseline in bone volumetric density at the 2nd metacarpal bone at 6th month

  Baseline to 6th month

• Changes from baseline in trabecular bone microarchitecture at 2nd metacarpal bone at 6th month

  Baseline to 6th month

• Changes from baseline in areal bone density at total hip at 6th month

  Baseline to 6th months

• Changes from baseline in areal bone density at lumbar spine at 6th month

  Baseline to 6th month

Study Arms (2)

Denosumab

EXPERIMENTAL

Patients in this arm will receive subcutaneous injection of denosumab 60mg every 6 months (1 dose for the study period).

Drug: Denosumab

Standard treatment

ACTIVE COMPARATOR

Patients (n=20) in this arm will receive oral alendronate (Fosamax®)70mg once.

Drug: Alendronate

Interventions

Denosumab DRUG

Subcutaneous injection of denosumab 60mg every 6 months (1 dose for study period)

Also known as: Prolia®

Denosumab

Alendronate DRUG

Alendronate 70mg once weekly

Also known as: Fosamax®

Standard treatment

Eligibility Criteria

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

You may qualify if:

• with a diagnosis of RA according to the 2010 new 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria
• at an age over 18 years old
• have a lumbar spine, or total hip or distal radius T-score lower than -1.5 by DXA
• without severe deformity in metacarpophalangeal (MCP) joints which would influence the longitudinal assessment of HR-pQCT
• consent to receive alendronate if randomized to standard treatment group.

You may not qualify if:

• they have previous use of denosumab, teriparatide, alendronate or other anti-resorptive agents;
• they have a history of recent major gastrointestinal (GI) tract disease (e.g. oesophagitis or GI ulceration) or have experienced any previous adverse reaction to bisphosphonate therapy;
• they are receiving other bone-active drugs, such as hormonal replacement therapy, thyroxine, thiazide and diuretics;
• they have conditions affecting bone metabolism; contraindications to alendronate and denosumab (uncorrected hypocalcemia);
• they have unexplained hypocalcemia;
• they have severe renal impairment or serum creatinine level of \>200umol/L;
• they are pregnant or breastfeeding;
• they do not understand Chinese or are incompetent in giving consent.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Shatin, N.t., Hong Kong

Location

Related Publications (1)

• Yue J, Griffith JF, Xiao F, Shi L, Wang D, Shen J, Wong P, Li EK, Li M, Li TK, Zhu TY, Hung VW, Qin L, Tam LS. Repair of Bone Erosion in Rheumatoid Arthritis by Denosumab: A High-Resolution Peripheral Quantitative Computed Tomography Study. Arthritis Care Res (Hoboken). 2017 Aug;69(8):1156-1163. doi: 10.1002/acr.23133. Epub 2017 Jul 10.

  PMID: 27768831 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Denosumab; Alendronate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Study Officials

• Lai-Shan Tam, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 3, 2013
• First Posted: January 17, 2013
• Study Start: December 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: September 11, 2014

Record last verified: 2014-09

Locations

HK (1)