Denosumab In Addition To Intense Urate-Lowering Therapy for Bone Erosions

NCT02903446 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: F160315004
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Bone erosions are a common manifestation and feature of structural damage in severe/chronic tophaceous gout. Management of this destructive and often debilitating gout complication has focused exclusively on urate-lowering therapy (ULT) to reduce frequency of gout attacks, but little attention has been given to prevention or reversal of gout related bone erosions and other structural damage to bone caused by gout. Since there is no known effective treatment to attenuate or improve structural damage caused by gout, we propose a pilot, controlled, proof-of-concept study in which denosumab, an FDA approved medication for the treatment of bone loss, will be added to standard ULT in 20 patients with erosive gout.

Conditions

Gout

Outcome Measures

Primary Outcomes (1)

• CT Bone Erosion Score

  Change in the foot CT bone erosion score from baseline to 12 months. A total of 14 bones of the foot are scored. Each bone of the scored separately on a scale from 0 to 10, based on the proportion of eroded bone compared with the 'assessed bone volume', judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2: 11-20% bone eroded; 3:21-30% of bone eroded; 4: 31-40% of bone eroded; 5: 51-60% bone eroded; 7:61-70% of bone eroded; 8: 71-80% of bone eroded; 9: 81-90% bone eroded; 10:\>=91% of bone eroded. Higher score indicates worsening of erosion. Score ranges from 0 to 140.

  Baseline, 12 months

Secondary Outcomes (5)

• Decrease in Bone Reabsorption

  Baseline, 12 months

• Change in Subject Reported Functional Status (Disability)

  Baseline, 12 months

• Subject Reported Change in Physical Health

  Baseline, 12 months

• Subject Reported Change in Mental Health

  Baseline, 12 months

• Assessment of Pain

  Baseline, 12 months

Study Arms (2)

Intervention

ACTIVE COMPARATOR

Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care

Drug: Denosumab

Control

NO INTERVENTION

Standard urate lowering therapy

Interventions

Denosumab DRUG

Participants will be randomized (1:1) allocation to denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + ULT standard of care OR ULT standard of care therapy

Also known as: Prolia

Intervention

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 30 years or older and able to provide informed consent
• Diagnosis of gout according to the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria
• Radiographic foot bone erosion attributable to gout and confirmed by a radiologist
• Serum urate of ≤ 5 mg/dL (300 µmol/L) or less\*

You may not qualify if:

• Treatment with bisphosphonates in the preceding 2 years
• Any prior treatment with denosumab
• Women of childbearing potential, who are not currently using birth control, are pregnant, planning to become pregnant, or are breast-feeding
• Men planning to conceive in the next 12 months
• Unstable systemic medical condition
• Uncontrolled hyperthyroidism
• Uncontrolled hypothyroidism
• History of Addison disease
• History of osteomalacia
• History of osteonecrosis of the jaw (ONJ)
• History of atypical femur fracture
• History of tooth extraction, jaw surgery, dental implants, or other dental surgery within the prior 6 months
• History of anorexia nervosa, bulimia (by history or physical) or obvious malnutrition.
• Invasive dental work planned in the next 2 years
• History of Paget's disease of bone

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• University of Auckland, New Zealand: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Gout

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Angelo Gaffo, MD; Associate Professor
• Organization: UNIVERSITY OF ALABAMA AT BIRMINGHAM

agaffo@uab.edu

205-996-6086

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: September 16, 2016
• Study Start: February 1, 2017
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: November 2, 2021
• Results First Posted: August 31, 2021

Record last verified: 2021-10

Locations

US (1)