Clinical trial to assess the efficacy and tolerability of several escalating doses of clodronate, in patients with painful knee osteoarthritis

Phase 1

• Conditions: Patients with painful knee osteoarthritis; MedDRA version: 21.1Level: LLTClassification code 10029877Term: OA kneeSystem Organ Class: 100000004859; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2021-003124-33-IT
• Lead Sponsor: SPA-SOCIETÀ PRODOTTI ANTIBIOTICI S.P.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-01-03
• Last Update Posted: 28 August 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 296

Inclusion Criteria

•Female and male patients aged 50 up to 75 years at the signature of informed consent form (ICF).
•Diagnosis of knee OA according to the American College of Rheumatology, confirmed by Rx during the screening (a Rx performed in the last three (3) months before Screening Visit is accepted).
•Kellgren-Lawrence radiographic score between 2 and 3 degrees in the tibio-femoral joint.
•Symptomatic knee OA (pain) since at least 6 months with a knee pain (VAS) ranging between 40 and 80 mm (at Screening the figure should be confirmed at the Baseline).
•Female patients of childbearing potential must have a negative urine pregnan-cy test before receiving the first dose of study medication and they must com-ply with contraception methods as requested by the study protocol.
• A signed ICF by the patient after exhaustive study discussion with the investigators.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 146

Exclusion Criteria

•BMI > 35 kg/m2 (Class II obesity).
•Joint instability due to other reasons than knee OA, such as f.i. algo dystrophic syndrome, either partial or complete rupture of internal / externals ligaments, kneecap instability, etc.
•Otherwise located lower limb pain, such as hip pain.
•Other musculoskeletal disorders related to the target knee.
•Any treatment with IA drugs in the last three (3) month before Day 0- Baseline (including any formulation of corticosteroids, or hyaluronic acid injections).
•Corticosteroid use by any systemic route, and hyaluronic acid injections or in-tra-articular corticosteroids for any other joint in the previous month will be not permitted.
•Any treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) in the week before Baseline, or any steroid anti-inflammatory drugs and chon-droprotective drugs in the thirty (30) days before Base¬line.
•Any treatment with systemic bisphosphonates in the last twelve (12) months before Baseline.
•Any treatment with glucosamine or chondroitin sulfate, diacerein and matrix metalloproteinase (MMP) inhibitors in the 4 weeks before Base¬line.
•Any treatment with denosumab in the 12 months before Baseline.
•Any treatment with paracetamol in the twelve (12) hours before Base¬line.
•Any knee surgery in the past or knee arthroplasty.
•Any diagnostic or surgical arthroscopy of the knee in the six (6) months before Baseline.
•Any jaw osteonecrosis in the last twenty-four (24) months before Base¬line or at a risk of jaw osteonecrosis.
•Any known hypersensitivity to the drug in the study and to its excipients or other bisphosphonates, and any hypersensitivity to paracetamol (rescue drug).
•Any participation in a clinical study in which the last administration of the investigational medicinal product was within two (2) weeks before consenting to study participation (i.e. signing ICF).
•Inadequate organ function defined by the following laboratory parameters:
o Absolute Neutrophil Count (ANC) < 1500/^l
o Haemoglobin (Hb) < 9 g/dl (< Hb 5.6 mmol/L)
o Platelet Count < 100.000/^l
o Serum Creatinine > 1.5 x ULN or eGFR < 60 mL/min (as per Cockroft-Gault formula)
o ALT or AST > 1.5 x ULN
o Serum Total Bilirubin > 1.5 x ULN
•Pregnant or breastfeeding women, or women planning to become pregnant during the study.
•Any positive or suspected history of alcoholism or drug use.
•Clinically significant (i.e.) gastrointestinal, renal, hepatic, pulmonary, cardiovascular or neurological disease that could interfere with the outcome of the study or the patient’s ability to comply with study requirements.
•Patients unwilling or unable to comply with the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified