Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy of Denosumab 60mg sc Every 3 Months in Patients With Erosive Osteoarthritis of the Interphalangeal Finger Joints

University Hospital, Ghent1 site in 1 country100 target enrollmentMarch 2016

Overview

Brief Summary

This is a randomized, double blind placebo controlled one-site proof-of-concept study in subjects with erosive osteoarthritis (OA) of interphalangeal (IP) finger joints.

A total of 100 subjects will be enrolled into the study: 48 weeks placebo controlled double-blind phase with denosumab 60mg every 12 weeks, followed by a 48-week open-label phase in which all subjects will receive denosumab.

Detailed Description

Investigational therapy: denosumab 60mg subcutaneous injection every 12 weeks. All subjects will receive Calcium/vit D supplementation. Efficacy objectives: The primary objective is to assess the effect of denosumab on the reduction of radiographic erosive progression using GUSS (Ghent University Score System). The secondary objective is to assess the effect of denosumab on the reduction of radiographic erosive progression as defined by diminishing the appearance of new erosive IP finger joints. The exploratory objective is mainly to assess the effect of denosumab on clinical variables, as well as ultrasonography and DEXA (dual energy x-ray absorptiometry) parameters.

Registry

clinicaltrials.gov

Start Date

March 2016

End Date

April 28, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University Hospital, Ghent

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•• Subjects with hand OA having suffered from transient inflammatory attacks of the interphalangeal finger joints characteristic for what has been termed 'inflammatory' or 'erosive' hand OA.
•Subjects with hand OA showing inflammatory signs, either clinically or ultrasonographically, of the interphalangeal finger joints.
•Subjects with hand OA in which at least 1 interphalangeal finger joint has the typical appearance on the X-rays of a 'J' or 'E' phase joint as defined by the criteria mentioned above.
•Subjects with hand OA where at least 1 interphalangeal finger joint in the 'J' or 'E' phase presents a palpable swelling.

Exclusion Criteria

•• Patients with known hypersensitivities to mammalian-derived drug preparations.
•Patients with clinically significant hypersensitivity to any of the components of Prolia.
•Current and/or Prior treatment with any investigational agent within 90 days, or five half-lives of the product, whichever is longer.
•Previous administration of denosumab from clinical trials or others (e.g. commercial use).
•Vitamin D deficiency \[25(OH) vitamin D level \< 20 ng/mL (\< 49.9 nmol/L)\]. Possibility of replenishment and re-screening.
•Subjects with current hypo- or hypercalcemia (normal serum calcium levels: 8.5-10.5 mg/dl or 2.12-2.62 mmol/L).
•Patients currently under bisphosphonate (BP) treatment or any use of oral BPs within 12 months of study enrollment or intravenous BPs or strontium ranelate within 5 years of study enrollment
•Prior use of any chondroprotective drug within 90 days e.g. chondroitin sulfate, glucosamine, avocado-soybean unsaponifiables, tetracyclins, corticosteroids.
•Prior use of any immunomodulating drug with possible effects on proinflammatory cytokine metabolism within 90 days a.o. corticosteroids, methotrexate, sulfasalazine, leflunomide, D-Penicillin, anti-malarials, cytotoxic drugs, TNF (tumor necrosis factor) blocking agents.
•History of drug or alcohol abuse in the last year.

Arms & Interventions

Experimental: denosumab

50 patients will be enrolled in this group for a total treatment duration of 24 months (96 weeks): 48 weeks denosumab 60mg sc every 12 weeks followed by a 48-weeks open label phase denosumab 60mg sc every 12 weeks. Calcium and vit D supplementation will be installed at baseline.

Intervention: denosumab

Experimental: denosumab

50 patients will be enrolled in this group for a total treatment duration of 24 months (96 weeks): 48 weeks denosumab 60mg sc every 12 weeks followed by a 48-weeks open label phase denosumab 60mg sc every 12 weeks. Calcium and vit D supplementation will be installed at baseline.

Intervention: Calcium/Vit D supplementation

Comparator

50 patients will be enrolled in this group for a total treatment duration of 24 months (96 weeks): 48 weeks placebo sc every 12 weeks followed by a 48-weeks open label phase denosumab 60mg sc every 12 weeks. Calcium and vit D supplementation will be installed at baseline

Intervention: denosumab

Comparator

50 patients will be enrolled in this group for a total treatment duration of 24 months (96 weeks): 48 weeks placebo sc every 12 weeks followed by a 48-weeks open label phase denosumab 60mg sc every 12 weeks. Calcium and vit D supplementation will be installed at baseline

Intervention: Placebo

Comparator

50 patients will be enrolled in this group for a total treatment duration of 24 months (96 weeks): 48 weeks placebo sc every 12 weeks followed by a 48-weeks open label phase denosumab 60mg sc every 12 weeks. Calcium and vit D supplementation will be installed at baseline

Intervention: Calcium/Vit D supplementation

Outcomes

Primary Outcomes

Total Ghent University Scoring System (GUSS) of Target Joints at Week 24

Time Frame: 24 weeks

The Ghent University Scoring System, GUSS, is quantitative radiographic scoring system and found to be a reliable method to score radiographic change over time in erosive IP OA. It includes assessment of proportions of normal subchondral bone, subchondral plate and joint space over time. Range of score: min: 0 max:300. Change scores are measured where positive changes corresponds with remodeling or repair (better outcome), and negative changes with erosive progression (worse outcome).