Osteoarthritis of the knee MedDRA version: 12.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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 must also be willing to abstain from any intra-articular (i.a.) or peri-articular injections to the knee or surgery during the treatment period (12 weeks), except for the assigned study product. Part B only: • Pain in the index knee during the last 24 hours defined as a level of = 40 mm on a 100-mm VAS at baseline. The patients should also have had pain in the affected knee on most days over the last month. • Patients who are willing to discontinue all non-steroidal anti-inflammatory drugs (NSAIDs) or other analgesic medication taken for any condition, including their knee pain for 5 half lives of the current NSAID being used (3-7 days) before the baseline visit (see Section 5.5.6 and 5.5.7 for rescue and concomitant medication details). Patients who are on stable dose of opioids for at least 1 month before screening can continue to take their opioid at this stable dose throughout the study. The use of opioids must be documented in the eCRF. Patients must also be willing to abstain from any intra-articular (i.a.) or peri-articular injections to the knee or surgery during the treatment period (12 weeks), except for the assigned study product. • Patients who, if they are currently taking low dose aspirin (325 mg/day or less; as anti-coagulants), are willing to remain on a stable dose one month prior to screening and throughout the study. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients should not have rheumatoid arthritis (clinical assessment) or any connective tissue like disease (Lupus erythematosus, Sjögren Syndrome, or other autoimmune diseases). • Secondary osteoarthritis with history and/or any evidence in the index knee of the following diseases: septic arthritis, inflammatory joint disease, gout, Paget’s disease of the bone, articular fracture, major dysplasias or congenital abnormality, ochronosis, acromegaly, hemachromatosis, Wilson’s disease, primary osteochondromatosis, juvenile chronic arthritis with continued activity in adulthood, heritable disorders (e.g. hypermobility). Patients with secondary osteoarthritis following menisectomy or injuries of a collateral or cruciate ligament are not excluded. • USE OF OTHER BIOLOGICS OR INVESTIGATIONAL DRUGS AT THE TIME OF ENROLLMENT, OR WITHIN 30 DAYS OR 5 HALF-LIVES OF ENROLLMENT, WHICHEVER IS LONGER, OR INSTRUCTED BY LOCAL REGULATIONS. • SUBJECTS WITH KNOWN HYPERSENSITIVITY TO ANY BIOLOGICAL AGENTS (ANTIBODY OR SOLUBLE RECEPTOR), INCLUDING CANAKINUMAB. • PATIENTS WITH CONTRAINDICATIONS TO KNEE INJECTIONS (E.G. CUTANEOUS INFECTIONS AT THE KNEE, PSORIASIS AROUND THE KNEE, SEVERE COAGULOPATHY) ARE EXCLUDED. • PATIENTS WITH JOINT EFFUSION WHERE THERE IS SUSPICION OF AN INFECTED JOINT (E.G., FEVER, SUDDEN CHANGE IN EFFUSION SIZE OR JOINT PAIN, ETC.), SHOULD HAVE THE INFUSION ASPIRATED AND CULTURED PRIOR TO INCLUSION IN THE STUDY. IF THE CULTURE IS NEGATIVE, PATIENTS WOULD BE ELIGIBLE FOR PARTICIPATION. • Presence or history of underlying metabolic, endocrine, hematologic, pulmonary, cardiac, blood, renal, hepatic, infectious, psychiatric or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in a study of an immunomodulatory therapy. • Evidence of tuberculosis (TB) as as DEFINED BY LOCAL GUIDELINES/ LOCAL MEDICAL PRACTICE (at screening). • Subjects with evidence of hepatic (ALT, AST AST = 150% ULN or blood coagulation disorders (i.e. hemophilia, etc), anemia, idiopathic thrombocytopenic purpura, or gastrointestinal disorder: severe hepatic disease (Child-Pugh >9), history of alcohol and drug abuse; disease of gall bladder and pancreas; active peptic ulceration within the previous 6 months, gastrointestinal bleeding within the last 1 year (except history of minor lower gastro-intestinal tract bleeding, such as from hemorrhoids or anal fissures) or history of severe gastro-esophageal reflux disease or severe hiatus hernia; inflammatory bowel disease. • Hemoglobin less than 10 g/dl (women) or 12 g/dl (men) at screening. • Presence of severe renal function impairment (e.g. Estimated GFR (eGFR) using Modification of Diet in Renal Disease (MDRD) formula as of < 30 ml/min within past 6 months). History of renal trauma, glomerulonephritis, patients with one kidney, or renal failure requiring regular dialysis treatment. • History of malignancy within the previous 5 years (other than basal cell carcinoma or adequately treated carcinoma-in-situ of the cervix). REGARDLESS OF WHETHER THERE IS EVIDENCE OF LOCAL RECURRENCE OF METASTASES. • A positive HIV (ELISA and Western blot) test result, Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive pregnancy test (serum or urine).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. ;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. [...] ;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 | — |
Countries
Finland, France, Germany, United Kingdom
Outcome results
None listed