Adaptative, Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled, Clinical Trial, on the Efficacy and Tolerability of Different Escalating Doses of Intra-articular Clodronate in Patients With Painful Knee Osteoarthritis
The goal of this clinical trial is to to clarify which is the best dose of administration, to select a dose and to confirm the therapeutic efficacy of clodronate in patients with painful knee osteoarthritis (OA). The clinical trial will be divided in two parts. The main questions it aims to answer are: * in Phase II, to assess the safety and tolerability of different escalating doses of intra articular (IA) clodronate * in Phase II, to set a defined therapeutic dose (DTD) to be used in Phase III * in Phase III, to assess the safety and tolerability of different escalating doses of IA clodronate to confirm and extensively evaluate the therapeutic efficacy and safety of the clodronate DTD in patients with knee OA
• Female and male patients aged 50 up to 75 years at ICF signature.
• Diagnosis of knee OA according to the American College of Rheumatology, confirmed by Rx during the screening (a Rx performed in the last 3 months before Baseline is accepted).
• Kellgren-Lawrence radiographic score between 2 and 3 degrees in the tibiofemoral joint.
• 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).
• Female patients of childbearing potential must have a negative pregnancy test before each treat-ment and during the Visit 5 - Week 4 and they must use adequate methods of contraception throughout the course of the study.
• A signed ICF by the patient after exhaustive study discussion with the investigators.