A Phase 2a Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients with Knee Osteoarthritis
- Conditions
- ostheoarthritispain10023213
- Registration Number
- NL-OMON41808
- Lead Sponsor
- AbbVie B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 17
1.Subject must have radiographic evidence of knee osteoarthritis in the medial compartment of the index knee with Kellgren-Lawrence Grade 2 or 3 (with minimum 2 mm joint space width) during Screening as evaluated by a qualified central imaging reader. Prior radiographs taken
no more than 3 months before Study Day 1 with Synaflexer* can be submitted for centralized eligibility reading.
2. Subject must have either constant or intermittent index knee pain at least 14 days (regardless of the intensity) over the past 30 days at the initial screening visit. The intensity of index knee pain is between 4 and 8, inclusive, at the initial Screening Visit and Study Day 1 (as recorded on Question 1 of the Index Knee Pain Intensity Questionnaire).
3.Subject has one or more clinical signs and symptoms of active inflammation in the index knee as defined by (but not limited to) localized pain, joint stiffness, swelling and effusion during Screening Period and Study Day 1.
4.Presence of synovitis in the index knee confirmed either by ultrasound or MRI during Screening.
5.Subject discontinued analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and nutraceuticals (e.g., glucosamine, chondroitin sulfate, shark cartilage, diacerein, soy extract). The washout period will be at least 5 half-lives of the longest acting analgesic used, or 48 hours, whichever is longer prior to first dose of study drug.
1.History of major allergic reaction or significant sensitivity to any constituents of the study drug; or history of anaphylactic reaction to any agent (e.g., food products or bee stings) or history of a major reaction to any Immunoglobulin G (IgG) containing product.
2.Significant trauma or surgery to the index knee within the last year or arthroscopy of the index knee within 6 months of the initial Screening Visit.
3.Kellgren-Lawrence Grade 1 or 4 in the index knee.
4.Severe knee malalignment, either greater than 4.0° in varus; or greater than 8.0° in valgus angulation in the index knee.
5.Diagnosis of one or more of the following:
a.Inflammatory arthritis such as rheumatoid arthritis, autoimmune disorder, seronegative spondyloarthropathy, gout, or pseudogout (defined as acute episodic attacks of swollen , painful joints in a subject with X-Ray chondrocalcinosis or CPPD crystals);
b.Other chronic painful syndromes (such as Paget's disease and fibromyalgia) and clinically significant non-articular musculoskeletal pain that could interfere with assessment of pain at the index knee.
6. History or evidence of active tuberculosis (TB)
7. Any uncontrolled medical illness or unstable treatment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy:<br /><br>The primary efficacy comparisons will be between each of the ABT-981 treatment<br /><br>groups and the placebo treatment group for the primary efficacy measurement.<br /><br><br /><br>Safety:<br /><br>Safety analyses will be carried out using the safety population, which includes<br /><br>all patients who received at least one dose of study drug. Treatment-emergent<br /><br>adverse events and serious adverse events, which include pre- and<br /><br>post-treatment serious adverse events, will be summarized and reported.<br /><br><br /><br>Pharmacodynamic:<br /><br>Assessment of pharmacodynamic effects of ABT-981 on knee osteoarthritis will be<br /><br>explored by measuring several panels of biomarkers, such as MRI imaging<br /><br>biomarkers, biochemistry biomarkers, and clinical biomarkers.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Pharmacokinetic:<br /><br>Individual ABT-981 serum concentrations will be tabulated for each patient and<br /><br>treatment group and summarized with appropriate statistical methods.<br /><br>Immunogenicity data will be tabulated and summarized as appropriate. Synovial<br /><br>fluid ABT-981 concentrations will be compared to measurements in serum to<br /><br>determine the extent of synovial fluid distribution at steady-state.<br /><br><br /><br>Biomarkers:<br /><br>Summary statistics for all biomarkers at baseline and post-treatment time<br /><br>points, in addition to change from baseline at each time will be provided.</p><br>