Trial Outcomes & Findings for Denosumab In Addition To Intense Urate-Lowering Therapy for Bone Erosions (NCT NCT02903446)

NCT ID: NCT02903446

Last Updated: 2021-11-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: Baseline, 12 months
• Results posted on: 2021-11-02

Participant Flow

Potential study participants were screened for enrollment at rheumatology clinics located at the University of Alabama at Birmingham and the University of Auckland. Participants were recruited between March 2017 and May 2019.

Participant milestones

Measure	Intervention Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control Standard urate lowering therapy
Overall Study STARTED	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Intervention n=10 Participants Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control n=10 Participants Standard urate lowering therapy	Total n=20 Participants Total of all reporting groups
Age, Continuous	67 years STANDARD_DEVIATION 15 • n=5 Participants	63 years STANDARD_DEVIATION 9.4 • n=7 Participants	65.0 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized European descent	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Maori	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment New Zealand	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Serum Urate	4.3 mg/dL STANDARD_DEVIATION 0.5 • n=5 Participants	4.2 mg/dL STANDARD_DEVIATION 0.7 • n=7 Participants	4.3 mg/dL STANDARD_DEVIATION 0.6 • n=5 Participants
Estimated glomerular filtration rate	76.5 mL/min/1.73m2 STANDARD_DEVIATION 32 • n=5 Participants	72 mL/min/1.73m2 STANDARD_DEVIATION 15.3 • n=7 Participants	74.2 mL/min/1.73m2 STANDARD_DEVIATION 24.5 • n=5 Participants
CT Erosion Score (range 0-140 total of 14 bones)	6.6 units on a scale STANDARD_DEVIATION 5.4 • n=5 Participants	7.0 units on a scale STANDARD_DEVIATION 5.1 • n=7 Participants	6.8 units on a scale STANDARD_DEVIATION 5.1 • n=5 Participants
Serum CTX	316.6 pg/mL STANDARD_DEVIATION 152.6 • n=5 Participants	286.9 pg/mL STANDARD_DEVIATION 111.5 • n=7 Participants	303.4 pg/mL STANDARD_DEVIATION 133.0 • n=5 Participants
Health Assessment Questionnaire -Disability Index Total (range from 0-3.0)	0.36 HAQ Score STANDARD_DEVIATION 0.61 • n=5 Participants	0.39 HAQ Score STANDARD_DEVIATION 0.44 • n=7 Participants	0.38 HAQ Score STANDARD_DEVIATION 0.52 • n=5 Participants
Short Form Survey (SF-12) physical component score (range 0-100)	43.6 SF-12 score STANDARD_DEVIATION 11.9 • n=5 Participants	43.9 SF-12 score STANDARD_DEVIATION 7.3 • n=7 Participants	43.8 SF-12 score STANDARD_DEVIATION 9.6 • n=5 Participants
Short Form Survey (SF-12) mental component score (range 0-100)	57.5 SF-12 score STANDARD_DEVIATION 4.2 • n=5 Participants	55.1 SF-12 score STANDARD_DEVIATION 10.4 • n=7 Participants	56.3 SF-12 score STANDARD_DEVIATION 7.8 • n=5 Participants
Visual Analogue Pain Score (range 0-10)	2.2 visual analog pain scale STANDARD_DEVIATION 3.7 • n=5 Participants	1.3 visual analog pain scale STANDARD_DEVIATION 1.5 • n=7 Participants	1.8 visual analog pain scale STANDARD_DEVIATION 2.9 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 months

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.

Outcome measures

Measure	Intervention n=10 Participants Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control n=10 Participants Standard urate lowering therapy
CT Bone Erosion Score	6.6 Score on a scale Standard Deviation 5.4	7.0 Score on a scale Standard Deviation 5.1

SECONDARY outcome

Timeframe: Baseline, 12 months

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

Outcome measures

Measure	Intervention n=10 Participants Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control n=10 Participants Standard urate lowering therapy
Decrease in Bone Reabsorption	177.6 pg/mL Standard Deviation 143.1	324.1 pg/mL Standard Deviation 113.3

SECONDARY outcome

Timeframe: Baseline, 12 months

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.

Outcome measures

Measure	Intervention n=10 Participants Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control n=10 Participants Standard urate lowering therapy
Change in Subject Reported Functional Status (Disability)	.33 Difference in HAQ score from baseline Standard Deviation .30	.11 Difference in HAQ score from baseline Standard Deviation 0.24

SECONDARY outcome

Timeframe: Baseline, 12 months

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.

Outcome measures

Measure	Intervention n=10 Participants Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control n=10 Participants Standard urate lowering therapy
Subject Reported Change in Physical Health	45.5 units on a scale Standard Deviation 12.6	52.3 units on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Baseline, 12 months

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

Outcome measures

Measure	Intervention n=10 Participants Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control n=10 Participants Standard urate lowering therapy
Subject Reported Change in Mental Health	58.7 units on a scale Standard Deviation 6.7	53.1 units on a scale Standard Deviation 7.6

SECONDARY outcome

Timeframe: Baseline, 12 months

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

Outcome measures

Measure	Intervention n=10 Participants Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control n=10 Participants Standard urate lowering therapy
Assessment of Pain	1.3 units on a scale Standard Deviation 3.1	1.2 units on a scale Standard Deviation 1.4

Adverse Events

Intervention

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Control

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Intervention n=10 participants at risk Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care Denosumab: 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	Control n=10 participants at risk Standard urate lowering therapy
Cardiac disorders Atrial flutter	0.00% 0/10 • 1 year	10.0% 1/10 • Number of events 1 • 1 year
Cardiac disorders Atrial fibrillation	10.0% 1/10 • Number of events 1 • 1 year	0.00% 0/10 • 1 year
Gastrointestinal disorders Gastro-esophageal reflux	0.00% 0/10 • 1 year	10.0% 1/10 • Number of events 1 • 1 year
Gastrointestinal disorders Vomitting	10.0% 1/10 • Number of events 1 • 1 year	0.00% 0/10 • 1 year
Gastrointestinal disorders Esophageal refulx	0.00% 0/10 • 1 year	10.0% 1/10 • Number of events 1 • 1 year
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/10 • 1 year	10.0% 1/10 • Number of events 1 • 1 year
Musculoskeletal and connective tissue disorders Joint Pain	10.0% 1/10 • Number of events 1 • 1 year	10.0% 1/10 • Number of events 1 • 1 year
Musculoskeletal and connective tissue disorders Cramps	10.0% 1/10 • Number of events 1 • 1 year	0.00% 0/10 • 1 year
Skin and subcutaneous tissue disorders Skin Rash	10.0% 1/10 • Number of events 1 • 1 year	0.00% 0/10 • 1 year
Blood and lymphatic system disorders Anemia	0.00% 0/10 • 1 year	10.0% 1/10 • Number of events 1 • 1 year

Additional Information

Angelo Gaffo, MD; Associate Professor

UNIVERSITY OF ALABAMA AT BIRMINGHAM

Phone: 205-996-6086

Email: agaffo@uab.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place