RANKL-blockade for the Treatment of Erosive Osteoarthritis (OA) of Interphalangeal Finger Joints

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 (IP) Finger Joints

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.

Study Overview

• Status: Completed
• Conditions: Hand Osteoarthritis
• Intervention / Treatment: Drug: denosumab; Dietary supplement: Calcium/Vit D supplementation; Drug: Placebo

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 the Ghent University Score System (GUSS).

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 dual energy x-ray absorptiometry parameters.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • UZ Ghent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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, tumor necrosis factor (TNF) blocking agents.
• History of drug or alcohol abuse in the last year.
• Patients suffering from chronic inflammatory rheumatic disease (e.g. rheumatoid arthritis, spondylarthropathy, psoriatic arthritis, gout, chondrocalcinosis or other auto-immune diseases, e.g. systemic lupus erythematosus).
• History of cancer or lymphoproliferative disease other than a successfully and completely treated squamous cell or basal cell carcinoma of the skin or cervical dysplasia, with no recurrence within the last two years.
• History of any Solid Organ or Bone Marrow Transplant.
• Comorbidities: significant renal function impairment (glomerular filtration < 30 ml/min/1.73m2 or <50% of normal value), uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (NYHA III, IV), uncontrolled hypo or hyperparathyroidism, active inflammatory bowel disease, malabsorption, liver failure or chronic hepatic disease (serum aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) levels 3 times above normal), recent stroke (within three months), chronic leg ulcer and any other condition (e.g,. indwelling urinary catheter) which, in the opinion of the investigator, would put the subject at risk by participation in the protocol.
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures .
• Patient who is pregnant or planning pregnancy; if the female subject is of child-bearing age, she must use a valid mean of contraception during the study and for 9 months after last dose of study medication. For males with a partner of childbearing potential: subject refuses to use 1 effective methods of contraception for the duration of the study and for 10 months after the last dose of study medication.
• Female subjects who are breast-feeding.
• History of osteonecrosis of the jaw, and/or recent (within 3 months) tooth extraction or other unhealed dental surgery; or planned invasive dental work during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: denosumab; 60mg sc; Other Names: Active Comparator; Dietary supplement: Calcium/Vit D supplementation; Daily dosage Calcium 1000mg / Vit D 880 IU; Other Names: Steovit forte
Placebo Comparator: 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	Drug: denosumab; 60mg sc; Other Names: Active Comparator; Dietary supplement: Calcium/Vit D supplementation; Daily dosage Calcium 1000mg / Vit D 880 IU; Other Names: Steovit forte; Drug: Placebo; identical syringe; Other Names: placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Ghent University Scoring System (GUSS) of Target Joints at Week 24	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).	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of New Erosive Joints by Verbruggen and Veys at Week 48	These are the number of new erosive IP joints according to the Verbruggen and Veys anatomical scoring system amongst the pre-erosive joints (i.e., N, S, J joints) at 48 weeks.	48 weeks
Total Ghent University Scoring System (GUSS) at Week 48	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, and negative changes with erosive progression.	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of (Serious) Adverse Events	Number of patients who have experienced one or more (serious) adverse events throughout the study	48 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Amgen
• Investigators: Principal Investigator: Dirk Elewaut, Prof. Dr., UZ Ghent; Principal Investigator: August Verbruggen, Prof Dr. Em., UZ Ghent; Principal Investigator: Ruth Wittoek, Prof. Dr., UZ Ghent

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): June 26, 2019
• Study Completion (Actual): April 28, 2021

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (Estimated): May 13, 2016

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: denosumab; RANKL-blockade
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium; Denosumab
• Other Study ID Numbers: AGO/2015/008; 2015-003223-53 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO