A Multicenter, Randomized, Double-blind, Placebo- and Active-Controlled Phase III Study on the Safety and Efficacy of a Single Intra-articular Administration of JTA-004 in Symptomatic Knee Osteoarthritis
Overview
- Phase
- Phase 3
- Intervention
- JTA-004
- Conditions
- Symptomatic Osteoarthritis of the Knee
- Sponsor
- Bone Therapeutics S.A
- Enrollment
- 746
- Locations
- 20
- Primary Endpoint
- knee pain
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Osteoarthritis is a degenerative, chronic, and progressive joint disease considered as the most common joint disorder worldwide. In healthy joints, there is a continuous process of natural breakdown and repair of cartilage. This process becomes disrupted in OA, leading to degeneration and loss of articular cartilage, along with other joint changes, including subchondral bone remodeling, osteophyte formation, thickening of the capsule and sometimes inflammation of the synovia. JTA-004 is a plasma protein solution supplemented with HA and clonidine developed as a single IA injection for the treatment of knee OA. Local administration of JTA-004 into the joint cavity is intended to relieve chronic pain in subjects suffering from knee OA and discomfort associated with the IA administration.
The JTA-004 Phase III study is a placebo and active-controlled, randomized, double-blind study to evaluate the potential of a single, intra-articular injection of JTA-004 to reduce osteoarthritic pain in the knee at 3 months compared to placebo or active comparator. The study is expected to enrol 742 patients with mild to moderate symptomatic knee osteoarthritis in 22 centres in 6 European countries and Hong Kong SAR.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ambulatory (able to walk unassisted, the use of a crutch or a walking stick (only one) is allowed if already used at screening but should be avoided during the study up to the 6-month follow-up visit)
- •Diagnosed with primary knee OA, fulfilling the following American College of Rheumatology (ACR) criteria at the target knee:
- •Pain present for most days of the preceding month
- •Morning stiffness \< 30 minutes
- •Kellgren-Lawrence grade II or III (confirmed by appropriate X-rays taken within 6 months prior to screening visit)
- •Target knee pain ≥ 200 mm and ≤ 400 mm out of 500 mm on the WOMAC® VA3.1 pain questionnaire (sum of 5 questions) at screening and baseline
- •Insufficient/failed response or intolerance to analgesics and/or non-steroidal anti-inflammatory drugs (NSAIDs) as reported by the subject
- •Willing and able to abstain from initiation of physical therapy and of use of knee braces at the target knee up to the 6-month follow-up visit (a subject undergoing physical therapy or using knee braces at a stable frequency for at least 2 weeks prior to screening is allowed to continue at same frequency (frequency increase is not allowed))
- •Capable to understand and comply with study requirements and to provide a written, dated, and signed informed consent prior to any study procedure for participation in the study and transmission of personal "pseudo-anonymized" data
Exclusion Criteria
- •History of trauma or surgery or arthroscopy at the target knee within 12 months before inclusion
- •Concomitant inflammatory disease or other conditions affecting the joints (e.g., infectious arthritis, rheumatoid arthritis, psoriatic arthritis or spondyloarthropathy, Paget's disease, hemochromatosis...)
- •Any target knee abnormality that could impact safety or efficacy assessment
- •Microcrystalline arthropathies: chondrocalcinosis/calcium pyrophosphate dihydrate disease (pseudo-gout) or gout if believed likely to interfere with the study endpoints, in the opinion of the Investigator
- •Clinically significant valgus/varus deformities at the Investigator's discretion
- •Any musculoskeletal condition (such as symptomatic hip OA, amputation, neurologic disorder, chronic back pain with or without radiculopathy, sciatica) that would impede measurement of efficacy at target knee
- •Contralateral knee pain equal to or exceeding the pain in the target knee (on the WOMAC® VA3.1 pain questionnaire) at screening and/or baseline
- •Knee arthroplasty planned within 12 months after the screening visit Current or previous diagnoses, signs and/or symptoms
- •Uncontrolled diabetes mellitus (hemoglobin A1c \[HbA1c\] \> 10% or \> 86 mmol/mol), end-stage hepatic or renal disease (severe and clinically significant abnormalities according to local laboratory ranges) documented in the subject's file
- •Any relevant cardiovascular disease (severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease) or any clinically significant electrocardiogram (ECG) abnormality as judged by the Investigator
Arms & Interventions
JTA-004
single knee intra-articular injection of JTA-004 solution (2ml)
Intervention: JTA-004
placebo
single knee intra-articular injection of saline solution (2ml)
Intervention: placebo
Hylan G-F 20
single knee intra-articular injection of Hylan G-F 20 (6ml)
Intervention: Hylan G-F 20
Outcomes
Primary Outcomes
knee pain
Time Frame: 3 months
Difference between JTA-004 and placebo in mean change from baseline in knee pain at Month 3 using the Western Ontario McMaster University (WOMAC®) Visual Analogue 3.1 pain subscale (subscale A; score 0 (no-pain)-100 (worst imaginable pain) mm).
Secondary Outcomes
- knee pain(6 months)
- Knee pain(3 months)
- knee physical function(3 months)
- Patient Global assessment(3 months)
- physical function(6 months)
- subject global health and well-being(3 months)
- responder rate(3 months)