A randomized, double blind, placebo and Naproxen controlled, multi-center, study to determine the safety, tolerability, pharmacokinetics and effect on pain of a single intra-articular administration of Canakinumab (anti-IL1β antibody) in patients with osteoarthritis in the knee

INTERVENTION: Trade Name: ILARIS Product Name: Canakinumab Product Code: ACZ885 Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: CANAKINUMAB CAS Number: 914613‐48‐2 Current Sponsor code: ACZ885 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Powder for solution for injection Route of administration of the placebo: Intraarticular use Trade Name: Naproxen Hexal Product Name: Naproxen Pharmaceutical Form: Tablet INN or Proposed INN: NAPROXEN CAS Number: 22204‐53‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Osteoarthritis of the knee ; MedDRA version: 12.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis INCLUSION CRITERIA: • Written informed consent must be obtained before any assessment is performed. • Male and female patients aged 40 ‐ 80 years (inclusive). • Diagnosis of knee osteoarthritis in the index knee (in patients with bilateral osteoarthritis, the more symptomatic knee will be used) as determined by the American College of Rheumatology criteria (Altman R. et al, 1986); Kellgren‐Lawrence grade (KLG) 2 to 3. • Radiographic evidence of tibiofemoral compartment osteoarthritis of the index knee within 6 months before screening (using weight bearing anteroposterior radiographs) is required. • BMI = 45 kg/m2. Part A only: • Patients must be willing to discontinue all non‐steroidal anti‐inflammatory drugs (NSAIDs) or other analgesic medication (including opiods) taken for any condition, including their knee pain 24 hours before the baseline visit and until the assessment on Day 4. Rescue medication is allowed as described in Section 5.5.6. Patients mu PRIMARY OUTCOME: Main Objective: Part A: To determine the safety and tolerability of single ascending doses of an intra‐articular administration of ACZ885 in subjects with osteoarthritis in the knee.; ; Part B: To evaluate the clinical benefit in subjects with osteoarthritis in the knee, as measured by the change in the pain by using 100 mm VAS scale from baseline to day 4 (primary) and in the Western Ontario and McMaster osteoarthritis Index (WOMAC) pain subscale from baseline to week 4 (step‐down primary) of a single administration of ACZ885 (i.a.) in comparison to placebo.; Primary end point(s): Part A: To determine the safety and tolerability of single ascending doses of an intra‐articular administration of ACZ885 in subjects with osteoarthritis in the knee.; ; Part B: To evaluate the clinical benefit in subjects with osteoarthritis in the knee, as measured by the change in the pain by using 100 mm VAS scale from baseline to day 4 (primary) and in the Western Ontario and McMaster osteoarthritis Index (WOMAC) pain subscale from baseline to week 4 (step‐down primary) of a single administration of ACZ885 (i.a.) in comparison to placebo.; Secondary Objective: Part B only:; 1) To evaluate the clinical benefit in subjects with osteoarthritis in the knee, as measured by the change in the pain by using VAS score and in the WOMAC pain subscale as well as the WOMAC function subscale and WOMAC stiffness subscale from baseline up to week 12 (at each clinical visit), of a single administration of ACZ885 (i.a.) in comparison to placebo. ; 2) To estimate the percentage of responders at each post baseline visit in the pain 100 mm VAS scale as achievement of = 50% reduction from baseline.; 3) To characterize the amount of rescue analgesic used and time to analgesic reintroduction.; 4) To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiling of ACZ885 and assess the PK / PD relationships following intra‐articular administration.; 5) To determine the physician’s global assessment of the status of treatment response (post‐dose at each clinical visit) using a 5 point Likert scale.; [...]; ;