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

NCT02771860 | Completed Phase 2 Results

• 2 other identifiers: AGO/2015/0082015-003223-53
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Hand Osteoarthritis

Keywords

denosumab; RANKL-blockade

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of New Erosive Joints by Verbruggen and Veys at Week 48

  48 weeks

• Total Ghent University Scoring System (GUSS) at Week 48

  48 weeks

Other Outcomes (1)

• Number of (Serious) Adverse Events

  48 weeks

Study Arms (2)

Experimental: denosumab

ACTIVE COMPARATOR

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; Dietary Supplement: Calcium/Vit D supplementation

Comparator

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

Drug: denosumab; Drug: Placebo; Dietary Supplement: Calcium/Vit D supplementation

Interventions

denosumab DRUG

60mg sc

Also known as: Active Comparator

Comparator; Experimental: denosumab

Placebo DRUG

identical syringe

Also known as: placebo comparator

Comparator

Calcium/Vit D supplementation DIETARY_SUPPLEMENT

Daily dosage Calcium 1000mg / Vit D 880 IU

Also known as: Steovit forte

Comparator; Experimental: denosumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 .

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Amgen: collaborator

Study Sites (1)

UZ Ghent

Ghent, 9000, Belgium

Location

MeSH Terms

Interventions

Denosumab

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: Prof. dr. Ruth Wittoek
• Organization: University Gent

anuschka.vandenbogaert@uzgent.be

+3293322522

Study Officials

• Dirk Elewaut, Prof. Dr.

  UZ Ghent

  PRINCIPAL INVESTIGATOR

• August Verbruggen, Prof Dr. Em.

  UZ Ghent

  PRINCIPAL INVESTIGATOR

• Ruth Wittoek, Prof. Dr.

  UZ Ghent

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: May 13, 2016
• Study Start: March 1, 2016
• Primary Completion: June 26, 2019
• Study Completion: April 28, 2021
• Last Updated: September 25, 2024
• Results First Posted: September 25, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)