Clodronate disodium for Knee osteoarthritis

Inclusion criteria

• {"criterion_text":"- Female and male patients aged 50 up to 75 years at the signature of informed consent form (ICF)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Kellgren-Lawrence radiographic score between 2 and 3 degrees in the tibiofemoral joint."}
• {"criterion_text":"- Symptomatic knee OA (pain) since at least 6 months with a knee pain (VAS) ranging between 40 and 80 mm at Screening visit (the figure should be confirmed at Baseline)."}
• {"criterion_text":"- Female patients of childbearing potential must have a negative pregnancy test before each treatment and during the Visit 5 – Week 4 and they must use adequate methods of contraception throughout the course of the study."}
• {"criterion_text":"- A signed ICF by the patient after exhaustive study discussion with the investigators."}

Exclusion criteria

• {"criterion_text":"- BMI > 35 kg/m2 (Class II obesity)."}
• {"criterion_text":"- Any treatment with denosumab in the 12 months before Baseline."}
• {"criterion_text":"- Any treatment with paracetamol in the twelve (12) hours before Baseline."}
• {"criterion_text":"- Any knee surgery in the past or knee arthroplasty."}
• {"criterion_text":"- Any diagnostic or surgical arthroscopy of the knee in the six (6) months before Baseline."}
• {"criterion_text":"- Any jaw osteonecrosis in the last twenty-four (24) months before Baseline or at a risk of jaw osteonecrosis."}
• {"criterion_text":"- Any known hypersensitivity to the drug in the study and to its excipients or other bisphosphonates, and any hypersensitivity to paracetamol (rescue drug)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Inadequate organ function defined by the following laboratory parameters: Absolute Neutrophil Count (ANC) < 1500/^l ; Haemoglobin (Hb) < 9 g/dl (< Hb 5.6 mmol/L) ; Platelet Count < 100.000/^l ; Serum Creatinine > 1.5 x ULN or eGFR < 60 mL/min (as per Cockroft-Gault formula) ; ALT or AST > 1.5 x ULN ; Serum Total Bilirubin > 1.5 x ULN"}
• {"criterion_text":"- Pregnant or breastfeeding women, or women planning to become pregnant during the study."}
• {"criterion_text":"- Any positive or suspected history of alcoholism or drug use."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients unwilling or unable to comply with the protocol."}
• {"criterion_text":"- Otherwise located lower limb pain, such as hip pain."}
• {"criterion_text":"- Other musculoskeletal disorders related to the target knee."}
• {"criterion_text":"- Any treatment with IA drugs in the last three (3) month before Day 0- Baseline (including any formulation of corticosteroids, or hyaluronic acid injections)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 Baseline."}
• {"criterion_text":"- Any treatment with systemic bisphosphonates in the last twelve (12) months before Baseline."}
• {"criterion_text":"- Any treatment with glucosamine or chondroitin sulfate, diacerein and matrix metalloproteinase (MMP) inhibitors in the 4 weeks before Baseline."}

Primary endpoints

• {"endpoint_text":"- A clodronate dose will be considered as effective when a ≥ 8.5 mm reduction in the VAS of knee pain will be observed at Week 7 vs. Placebo.","definition_or_measurement_approach":"Measured using the Visual Analogue Scale (VAS) for knee pain at Week 7; effectiveness defined as a ≥ 8.5 mm reduction vs. placebo."}

Secondary endpoints

• {"endpoint_text":"- Mean changes in the VAS of knee pain observed at each other visit than Week 7 vs. Placebo and vs Baseline.","definition_or_measurement_approach":"Mean change in VAS of knee pain at each study visit compared with placebo and baseline."}
• {"endpoint_text":"- Mean changes in the VAS of knee pain observed 120 minutes after IA injection at Baseline, Weeks 1, 2 and 3 vs predose assessment.","definition_or_measurement_approach":"Mean change in VAS measured 120 minutes post intra-articular injection at specified visits versus predose assessment."}
• {"endpoint_text":"- Mean changes in the Lequesne Algo-functional Index at each visit vs Placebo and vs Baseline.","definition_or_measurement_approach":"Mean change in Lequesne Algo-functional Index at each visit compared with placebo and baseline."}
• {"endpoint_text":"- Mean changes in the WOMAC Index at each visit vs Placebo and vs Baseline.","definition_or_measurement_approach":"Mean change in WOMAC index at each visit compared with placebo and baseline."}
• {"endpoint_text":"- Mean changes in the Range of Motion at each visit vs Placebo and vs Baseline.","definition_or_measurement_approach":"Mean change in knee range of motion (extension/flexion) at each visit compared with placebo and baseline."}
• {"endpoint_text":"- Use of rescue drug consumption (paracetamol) across the patients visits.","definition_or_measurement_approach":"Measurement of paracetamol consumption (rescue medication) across patient visits."}

Italy

Earliest CTIS Part Ii Submission Date

15-02-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

804

Number Of Sites

14

Number Of Participants

278

Primary sponsor

Full Name

Spa Societa Prodotti Antibiotici S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Product Life Italia S.r.l.","duties_or_roles":"sponsorDuties codes: 1,10,11,5,6,8","organisation_type":"Pharmaceutical company"}