Osteoarthritis (OA) is a disease with a complex pathophysiology leading to the degeneration of articular cartilage and bone. It is characterized by pain, biochemical and enzymatic changes, cartilage loss, osteophyte formation and bone sclerosis. The pathological changes can be focal or more generalized and often correlate poorly with clinical symptoms and signs. Most available treatments act on symptoms (e.g. pain) without any benefits on the structural changes caused by OA.
Conditions
Interventions
Product Name: AAE581 10 mg coated tablets
Product Code: AAE581
Pharmaceutical Form: Coated tablet
INN or Proposed INN: balicatib
CAS Number: 354813-19-7
Current Sponsor code: AAE581
Other descriptive
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients with knee osteoarthritis aged from 40 to 80 years old. 2. Patients having at least one knee with OA with Kellgren and Lawrence grade 3. The other knee can be Kellgren and Lawrence grade 0 to 4. Patients should have significant OA pain in the knee (VAS > 40/100 mm) for most of the days in the past month. Patients who are controlled with analgesic medication are also allowed in the study provided their OA pain would be significant without this treatment. 3. Patients with elevated levels of CTX-II (value > 300 ng/mmol creatinine) 4. Patients suffering from osteoarthritis with at least one of the following risk facotrs: Obesity (BMI > 28) OA present at other sites, e.g. the hand, hip or spine Effusion in the target knee by clinical exam Family history of Total Joint Replacement 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: 1. Women with childbearing potential, e.g. post-menopausal for less than two years or with serum follicle stimulating hormone (FSH) level = 40 IU/ml, estradiol > 20 pg/mL or not surgically sterilized 2. Conditions causing secondary OA, primary fibromyalgia 3. Patients with current history or present signs of severe or uncontrolled renal insufficiency (serum creatinine >=125% ULN or presence of proteinuria (dipstick "+" or greater) not assosiated with urinary tract infection or evidence of sample contamination), hepatic (AST, ALT>= 150% ULN), hematological, cardiac, pulmonary, neurological, or cerebral disease. 4. Treatment with Intraarticular corticosteroids in the target knee within the past 3 months, Intraarticular hyaluronic acid injections in the target knee within the past 6 months 5. Knee surgery within the past 12 months and any planned knee surgery during the course of the study (including artheroscopy) 6. Patients with a BMI = 34
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of three different oral daily doses (10, 25 and 50 mg) of AAE581 versus placebo on the change in total cartilage volume of the target knee over time up to 12 months evaluated by MRI to obtain the dose for the phase III development program.;Secondary Objective: - To assess cartilage degradation by measuring change in cartilage lesion score measured by MRI, change in bone marrow edema score measured by MRI, and change in JSW narrowing measured by X-ray - To assess change in bone marker CTX-I, change in cartilage maker CTX-II and change in inflammation markers (hsCRP) - To assess the change in pain and function (Change in the mean number of days per month of analgesic consumption, Pain evaluation of the knee by pain VAS, patient’s global assessments (VAS), WOMAC® scores and response to treatment according to OMERACT-OARSI criteria) ;Primary end point(s): To assess the efficacy of 3 different oral daily doses (10, 25 and 50 mg) of AAE581 versus placebo on the change in total cartilage volume of the target knee after 12 months evaluated by MRI to obtain the dose for the phase III development program. | — |
Countries
Germany, Italy
Outcome results
None listed