Osteoarthritis MedDRA version: 8.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis
Conditions
Sponsors
Genzyme Europe BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient may be enrolled in this study if he/she meets all of the following criteria: Screening: 1. Provides signed written informed consent. 2. Is able to read and understand the language and content of the study material, understand the requirements for follow-up visits, and is willing to provide information at the scheduled evaluations. 3. Is a male or female patient aged 40 years or older 4. Is ambulatory (assistive devices are allowed if used 3 months or more prior to Screening) with an active lifestyle and in good general health 5. Has documented diagnosis of OA of the target knee where the disease has existed for at least 3 months prior to Screening. Radiographic evidence of OA of the target knee at screening is considered adequate 6. Currently meets American College of Rheumatology (ACR) Criteria for OA as noted below: o Knee pain for most days of prior month, and o Osteophytes at joint margins (radiograph) OR o Knee pain for most days of prior month, and o Synovial fluid typical of OA (laboratory), and o Morning stiffness = 30 minutes in duration, and o Crepitus on active joint motion OR o Knee pain for most days of prior month, and o Age = 40 years, and o Morning stiffness = 30 minutes in duration, and o Crepitus on active joint motion 7. Has continued target knee OA pain despite conservative treatment (e.g., weight reduction, physical therapy, analgesics) 8. Is willing to withhold intake of NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors) and analgesics, for a washout period of up to 21 days (depending on medication). 9. Is willing to discontinue prohibited treatments and medications throughout the study duration 10. Is willing to withhold intake of pain medications for 48 hours prior to all study visits Baseline: 11. If female, must have a negative serum pregnancy test (at Screening) and use a medically acceptable form of contraception for at least 1 month prior to Screening and continue use for the duration of the study. Otherwise, females must be surgically sterile, or postmenopausal (as documented in medical history) for at least 1 year. 12. Continues to meet all Screening inclusion/exclusion criteria 13. Has completed the pain and OA medication washout period 14. Has pain in the target knee as demonstrated by a score of 2 or 3 on the WOMAC LK 3.1 A1 15. Has a mean score of 1.5 to 3.5 on the WOMAC LK 3.1 A at Baseline (Day 0) 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: A patient will be excluded from this study if he/she does not meet the specific inclusion criteria, or if he/she is/has: 1. Modified Kellgren-Lawrence Numerical Grading System of grade 0 or grade IV for the target knee confirmed by radiographs performed within 3 months prior to Screening (see definitions below): (0) None: No Features of OA (IV) Severe: Joint space greatly impaired, with sclerosis of subchondral bone 2. Clinically apparent tense effusion of the target knee 3. Significant valgus/varus deformities, ligamentous laxity, or meniscal instability as assessed by the Investigator 4. Acute disease or trauma leading to secondary OA of the target knee within 10 years prior to screening 5. Viscosupplementation in any joint including the target knee within 12 months prior to Screening 6. Had arthroplasty at the target knee at any time or any other previous surgery in the target knee within the 6 months prior to Screening, or planned surgery throughout the duration of the study 7. Receiving physical therapy (at an outpatient/clinic setting) for the target knee that was initiated within 1 month before Screening 8. History of septic arthritis in any joint 9. Concomitant inflammatory disease or other condition that affects the joints (e.g., rheumatoid arthritis, metabolic bone disease, psoriasis, gout, chondrocalcinosis and active infection, etc.) 10. Symptomatic peripheral vascular disease of the study leg (prior or current) 11. Clinically significant venous or lymphatic stasis present in the study leg 12. Using protocol-prohibited medication/treatments for chronic pain that patient cannot be withdrawn from prior to study treatment at Baseline and throughout the duration of the study 13. Any musculoskeletal condition that would impede measurement of efficacy at the target knee 14. Symptomatic OA of the contralateral knee or of the ipsilateral hip, or symptomatic patello-femoral OA of the target knee, that is not responsive to acetaminophen / paracetamol (APAP) and requires other therapy 15. Systemic, or IA injection of corticosteroids in any joint within 3 months prior to Screening 16. Active infection, or history of an infection within the past 12 months, in the area to be injected 17. Any significant chronic skin disorder that could interfere with evaluation of the injection site 18. Heparin or crystalline warfarin (i.e., Coumadin®) anticoagulant therapy 19. Any known contraindication to acetaminophen/paracetamol (APAP 20. Any known contraindication to IA corticosteroids 21. Started the use of glucosamine, chondroitin sulfate, diacerhein, or avocado/soya extracts within 2 months prior to Screening 22. Uncontrolled diabetes mellitus, diabetic neuropathy, or infectious complications; end-stage hepatic or renal disease; or patients on immunosuppressive therapy 23. Current malignancy or treatment for malignancy within the past 5 years, except non-melanoma skin cancer 24. Active asthma that may require periodic treatment with systemic steroids during the study period (note: inhaled steroids for this condition are allowed)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study has two primary objectives: The first objective of this study is to compare the safety and efficacy of 1 x 4-mL and 2 x 4-mL IA injections of AVS-beta against 1 x 1-mL (40 mg/mL) IA injection of methylprednisolone acetate in treating patients with symptomatic knee OA. Secondly, to demonstrate that the odds of positive response to treatment for symptomatic knee OA over 26 weeks (where positive response is defined with the OMERACT-OARSI [Pham et al., 2003, J Rheum] set of criteria) is higher in patients treated with a 1 x 4-mL and/or 2 x 4-mL IA injections of AVS-beta compared to patients treated with a course of methylprednisolone acetate ; Secondary Objective: Odds of positive response to treatment for symptomatic knee OA with a 1 and/or 2 x 4-mL IA injections AVS-beta compared to methylprednisolone acetate The differences between - WOMAC LK 3.1 A change from Baseline to Week 26 in AVS-beta and methylprednisolone acetate groups WOMAC LK 3.1 A1 over 26 weeks and from Baseline to Week 26 in AVS beta and methylprednisolone acetate groups WOMAC LK 3.1 A1 change from Baseline to Week 26 in AVS-beta and methylprednisolone acetate groups WOMAC LK 3.1 C (physical function subscale) over 26 weeks and from Baseline to Week 26 in AVS-beta and the methylprednisolone acetate groups Total WOMAC over 26 weeks and from Baseline to Week 26 in the AVS-beta and methylprednisolone acetate groups PTGA over 26 weeks and from Baseline to Week 26 in AVS-beta and methylprednisolone acetate group COGA over 26 weeks and from Baseline to Week 26 in AVS-beta and the methylprednisolone acetate groups ; Primary end point(s): Performances : Primary Efficacy Objective; This study has two primary objectives: | — |
Countries
United Kingdom
Outcome results
None listed