Clinical trial • Phase II • Musculoskeletal

ZOLEDRONIC ACID MONOHYDRATE for Knee osteoarthritis | Osteoarthritis of the knee

Phase II trial of ZOLEDRONIC ACID MONOHYDRATE for Knee osteoarthritis | Osteoarthritis of the knee.

Overview

Trial Therapeutic Area
Musculoskeletal
Trial Disease
Knee osteoarthritis | Osteoarthritis of the knee
Trial Stage
Phase II
Drug Modality
Small molecule|Monoclonal antibody

Key dates

Initial CTIS Submission Date
21-06-2024
First CTIS Authorization Date
10-07-2024

Trial design

Randomised, active arms: prolia (denosumab) 60 mg solution for injection in pre-filled syringe (subcutaneous injection, product name indicates 60 mg); zoledronic acid fresenius kabi 4 mg/5 ml concentrate for infusion (listed routes include topical in record) as topical zoledronic acid adjuvant therapy. comparator/placebo: sodium chloride (placebo) - product entries for topical and subcutaneous injection are listed (sodium chloride). exact dosing schedules beyond product labels not specified in the record.-controlled Phase II trial in Denmark.

Randomised
Yes
Comparator
Active arms: Prolia (denosumab) 60 mg solution for injection in pre-filled syringe (subcutaneous injection, product name indicates 60 mg); Zoledronic Acid Fresenius Kabi 4 mg/5 ml concentrate for infusion (listed routes include TOPICAL in record) as topical zoledronic acid adjuvant therapy. Comparator/placebo: Sodium chloride (placebo) - product entries for topical and subcutaneous injection are listed (SODIUM CHLORIDE). Exact dosing schedules beyond product labels not specified in the record.
Target Sample Size
107
Trial Duration For Participant
730

Eligibility

Recruits 107 Vulnerable population selected (isVulnerablePopulationSelected true). Informed and written consent is required from participants. Subject information and informed consent forms are provided (documents listed in trial record). No specific assent or proxy-consent procedures are described in the record..

Pregnancy Exclusion
pregnancy (positive pregnancy test) or at risk of becoming pregnant during the project (not using safe anti-conceptive agents like contraceptive pills, intra-uterine device (IUD), hormone depot injection, subdermal implantation of a contraceptive rod, hormone vaginal ring, transdermal depot hormone sticking plaster)
Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected true). Informed and written consent is required from participants. Subject information and informed consent forms are provided (documents listed in trial record). No specific assent or proxy-consent procedures are described in the record.

Inclusion criteria

  • {"criterion_text":"- primary knee osteoarthritis in capable men and women"}
  • {"criterion_text":"- sufficient bone quality for total cruxiate retaining knee arthroplasty"}
  • {"criterion_text":"- age above 18 years but maximum 75 years of age"}
  • {"criterion_text":"- informed and written consent"}

Exclusion criteria

  • {"criterion_text":"- neuromuscular or vascular disease in the affected leg"}
  • {"criterion_text":"- renal failure (GFR < 30 ml/min)"}
  • {"criterion_text":"- persistent hypocalcaemia"}
  • {"criterion_text":"- allergic to bisphosphonate or denusomab"}
  • {"criterion_text":"- sporadic or permanent need of systemic glucocorticoid treatment"}
  • {"criterion_text":"- active cancer"}
  • {"criterion_text":"- radiation or chemotherapy"}
  • {"criterion_text":"- poor dental status (increased risk of jaw-necrosis with bisphosphonates/denusomab)"}
  • {"criterion_text":"- high use of alcoholic beverages (women > 14, men > 21 units/week)"}
  • {"criterion_text":"- peroperatively found to be unsuitable for a primary knee arthroplasty"}
  • {"criterion_text":"- osteoporosis based on former diagnosis or preoperative DXA-scan"}
  • {"criterion_text":"- fracture sequelae or previous PTO or previous extensive knee surgery"}
  • {"criterion_text":"- need for a stem-elongation"}
  • {"criterion_text":"- NSAID postoperatively"}
  • {"criterion_text":"- pregnancy (positive pregnancy test) or at risk of becoming pregnant during the project (not using safe anti-conceptive agents like contraceptive pills, intra-uterine device (IUD), hormone depot injection, subdermal implantation of a contraceptive rod, hormone vaginal ring, transdermal depot hormone sticking plaster)"}
  • {"criterion_text":"- metabolic bone disease"}
  • {"criterion_text":"- rheumatoid arthritis"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Implant migration (RSA) measured continuously from baseline to followup (MTPM) and estimation of Continuous MTPM (MTPM migration > 0.2 mm between 12 and 24 months of follow-up) according to Ryd et al. (Ryd et al., 1995).","definition_or_measurement_approach":"Measured by radiostereophotogrammetric analysis (RSA); continuous MTPM with threshold defined as MTPM migration > 0.2 mm between 12 and 24 months per Ryd et al., 1995."}

Secondary endpoints

  • {"endpoint_text":"- DXA - Changes in Bone Mineral Density under the Tibial Tray and in proximity of the central stem.","definition_or_measurement_approach":"Measured by dual energy x-ray absorptiometry (DXA) to assess changes in periprosthetic bone mineral density."}
  • {"endpoint_text":"- Biomarkers - Bone resorption from baseline to follow-ups and correlation between bone density changes, biomarkers of bone resorption and implant migration","definition_or_measurement_approach":"Measurement of bone resorption biomarkers from baseline to follow-ups and correlation analyses between biomarkers, BMD changes and implant migration."}

Recruitment

Planned Sample Size
107
Recruitment Window Months
156
Consent Approach
Informed and written consent is required from participants. Subject information and informed consent forms are provided (multiple documents listed including 'PATIENTINFORMATION REGENEREX_tillgsprotokol' and Danish-titled consent forms). No specific mention of assent procedures or multilingual versions in the record, though document titles suggest Danish-language materials.

Geography

Total Number Of Sites
1
Total Number Of Participants
107

Denmark

Earliest CTIS Part Ii Submission Date
03-07-2024
Latest Decision Or Authorization Date
26-03-2025
Processing Time Days
266
Number Of Sites
1
Number Of Participants
107

Sites

Site Name
Aarhus Universitetshospital
Department Name
Department of Orthopaedics
Contact Person Name
Maiken Stilling
Contact Person Email
maiken.stilling@clin.au.dk
Number Of Participants
107

Sponsor

Primary sponsor

Full Name
Region Midtjylland
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Denmark

Third parties

  • {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Educational Institution"}

Investigational products

Investigational Product Name
Zoledronic Acid Fresenius Kabi 4 mg/5 ml koncentrat till infusionsvätska, lösning
Active Substance
ZOLEDRONIC ACID MONOHYDRATE
Modality
Small molecule
Routes Of Administration
TOPICAL
Route
TOPICAL
Authorisation Status
Authorised (marketingAuthNumber: 29891, authorisationCountryCode: FI)
Starting Dose
0.5 mg (maxDailyDoseAmount reported as 0.5 mg in record)
Maximum Dose
0.5 mg (maxTotalDoseAmount reported)
Investigational Product Name
Prolia 60 mg solution for injection in pre-filled syringe
Active Substance
DENOSUMAB
Modality
Monoclonal antibody
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Authorisation Status
Authorised (marketingAuthNumber: EU/1/10/618/001)
Starting Dose
60 mg
Maximum Dose
120 mg (maxTotalDoseAmount reported)
Investigational Product Name
SODIUM CHLORIDE (Placebo)
Active Substance
SODIUM CHLORIDE
Modality
Other
Routes Of Administration
SUBCUTANEOUS INJECTION|TOPICAL
Route
SUBCUTANEOUS INJECTION and TOPICAL (two product entries)
Authorisation Status
Not applicable / no marketing authorisation number listed
Starting Dose
maxDailyDoseAmount reported as 9 mg and 18 mg in product entries
Maximum Dose
18 mg (maxTotalDoseAmount reported)

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