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GoutPhase 2NCT02903446

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

A Phase 2 study testing Denosumab in people with Gout, run by University of Alabama at Birmingham at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 30 years and older
Conditions the study is for
Gout
What is being tested?
Denosumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
1 Feb 2017to 1 Mar 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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*

Who cannot join

  • 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
Show all 28Show fewer
  • 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
  • Other bone diseases which affect bone metabolism
  • Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)]†
  • Hypercalcemia
  • Elevated transaminases ≥ 2.0 x upper limit of normal (ULN)
  • Elevated total bilirubin > 1.5x ULN
  • History of any solid organ or bone marrow transplant
  • Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma)
  • Hypocalcemia
  • Poorly tolerant of ULT including allopurinol, febuxostat, or probenecid
  • Estimated glomerular filtration rate < 30 mL/minute/1.73 m^2
  • Current use of any biological therapy (eg. infliximab, etanercept, adalimumab, etc.)
  • Treatment history with pegloticase or another recombinant uricase
  • Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

Other trials in United States

About this study

Official title: Denosumab In Addition To Intense Urate-Lowering Therapy for Bone Erosions in Gout: A Pilot Study

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.

Read the detailed description

A recently published clinical trial with zoledronic acid failed to show an effect in improving bone erosions among individuals with chronic tophaceous gout, despite improvements in bone mineral density (BMD) and bone turnover markers. However, it is known that increased numbers of osteoclasts (cells that absorb bone tissue during growth and healing) in patients with tophaceous gout are most likely a result of enhanced osteoclast activity as these patients also have higher circulating levels of the protein receptor activator of nuclear factor kappa-B ligand (RANKL). RANKL has been identified to affect the immune system and control bone regeneration and remodeling.

Furthermore, peripheral blood cells and synovial fluid cells taken from patients with erosive gout preferentially formed osteoclast-like cells in the presence of RANKL. The number of osteoclasts formed significantly correlates with the number of tophi in gout patients.

Denosumab (Prolia®) is a fully human monoclonal antibody with a high affinity for RANKL that can bind and neutralize the activity of human RANKL. Given the relevance of RANKL in the mechanism of gouty erosions,a central hypothesis of this pilot study is that denosumab is more likely to precisely target RANKL and the mechanism of gouty erosions than zoledronic acid.

Conditions
Gout
Being tested
Denosumab
Medical subject headings
Gout

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DenosumabDrug

    Also called Prolia

    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

Study groups in NCT02903446
Study groupRoleWhat they receive
InterventionActive comparatorDenosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care
Receives: Drug: Denosumab
ControlNo interventionStandard urate lowering therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, 12 months

Secondary outcomes (5)

  1. Decrease in Bone Reabsorption

    Change in bone reabsorption as measured by serum carboxy-terminal collagen crosslinks (CTX) levels (pg/mL) over 12 months. Lower values represent varying degrees of suppression of normal bone turnover.

    The reference ranges for C-terminal telopeptide in serum are as follows:

    Female (premenopausal): 40-465 pg/mL Female (postmenopausal): 104-1008 pg/mL Male: 60-700 pg/mL

    Measured: Baseline, 12 months

  2. Change in Subject Reported Functional Status (Disability)

    Change in subject reported functional status (disability) by Health Assessment Questionnaire (HAQ) will be assessed from baseline over 12 months. 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 moderate to severe disability, and 2 to 3 severe to very severe disability.

    Measured: Baseline, 12 months

  3. Subject Reported Change in Physical Health

    Subject reported change in physical and mental health by Short Form Health Survey (SF-12) scores assessed from baseline over 12 months. Range 0-100 with higher scores representing better self-reported health.

    Measured: Baseline, 12 months

  4. Subject Reported Change in Mental Health

    Subject Reported Change in Mental Health on SF-12 mental component form. Range 0-100 with higher scores representing better self-reported health

    Measured: Baseline, 12 months

  5. Assessment of Pain

    Assessment of pain score by visual analogue scale (VAS) reported from baseline over 12 months. Range 0-10 with higher scores representing more pain.

    Measured: Baseline, 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2016 (estimated)
  2. Study start1 Feb 2017
  3. Primary completion1 Mar 2020
  4. Study completion1 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02903446
Sponsor's protocol ID
F160315004
Status last verified
Oct 2021
First submitted
13 Sep 2016
Last updated
2 Nov 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Denosumab in people with Gout, run by University of Alabama at Birmingham at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CT Bone Erosion Score (time frame: Baseline, 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02903446.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2021.

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