A Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients With Knee Osteoarthritis

Study Overview
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Brief Summary
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A Phase 2a, multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the safety, tolerability, efficacy and pharmacokinetic/pharmacodynamic effect of ABT-981 in patients with symptomatic, radiographic, and inflammatory knee osteoarthritis.

Official Title
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A Phase 2a Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients With Knee Osteoarthritis

Conditions
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Knee Osteoarthritis, Medial Compartment Knee Osteoarthritis

Intervention / Treatment
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* Biological: ABT-981
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Radiographic knee osteoarthritis with Kellgren-Lawrence Grade 2 or 3 Body Mass Index (BMI) 18-34 kg/m2 One or more clinical signs and symptoms of active inflammation in the index knee Exclusion Criteria: History of allergic reaction to any constituents of the study drug, or to any Immunoglobulin G (IgG)-containing product History of anaphylactic reaction to any agent Significant trauma or surgery to the index knee Severe knee malalignment Any uncontrolled medical illness or an unstable treatment or therapy

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-981 low dose<br>25 mg ABT-981 subcutaneous (SC) every 2 weeks (E2W) | Biological: ABT-981<br> <br> * Other names: Lutikizumab;|
| Experimental: ABT-981 medium dose<br>100 mg ABT-981 SC E2W | Biological: ABT-981<br> <br> * Other names: Lutikizumab;|
| Experimental: ABT-981 high dose<br>200 mg ABT-981 SC E2W | Biological: ABT-981<br> <br> * Other names: Lutikizumab;|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scores of the Index Knee at Week 16 | The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement. | Baseline, Week 16 | 
| Change From Baseline in Quantitative Synovitis of the Index Knee at Week 26 | Change in synovitis of the index knee was evaluated using quantitative magnetic resonance imaging (MRI) measurements. MRI quantitative synovitis of the index knee was defined by mean synovial membrane thickness. | Baseline, Week 26 | 
| Change From Baseline in Effusion Volume of the Index Knee at Week 26 |  | Baseline, Week 26 | 
| Change From Baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) Semi-Quantitative Synovitis/Effusion Score of the Index Knee at Week 26 | Semi-quantitative synovitis/effusion volume WORMS scores were scored as normal (0), < 33% of maximum estimated distention (1), 33% - 66% of maximum estimated distention (2), or > 66% of maximum estimated distention (3). | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline In Index Knee Pain Intensity at Week 16 | The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded. | Baseline, Week 16 | 
| Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 16 | The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement. | Baseline, Week 16 | 
| Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 26 | The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 52 | The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement. | Baseline, Week 52 | 
| Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 26 | The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 52 | The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement. | Baseline, Week 52 | 
| Change From Baseline in Global Total Bone Marrow Lesion (BML) Score of the Index Knee Magnetic Resonance Imaging (MRI) at Week 26 | BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; < 25% of region), 2 (moderate; 25% - 50% of region), or 3 (severe; > 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe). | Baseline, Week 26 | 
| Change From Baseline in Global Total BML Score of the Index Knee MRI at Week 52 | BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; < 25% of region), 2 (moderate; 25% - 50% of region), or 3 (severe; > 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe). | Baseline, Week 52 | 
| Change From Baseline in Index Knee Intermittent and Constant Osteoarthritis Pain (ICOAP) Scores at Week 16 | The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain). | Baseline, Week 16 | 
| Change From Baseline in Index Knee ICOAP Scores at Week 26 | The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain). | Baseline, Week 26 | 
| Change From Baseline in Index Knee ICOAP Scores at Week 52 | The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain). | Baseline, Week 52 | 
| Change From Baseline In Index Knee Pain Intensity at Week 26 | The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded. | Baseline, Week 26 | 
| Change From Baseline In Index Knee Pain Intensity at Week 52 | The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded. | Baseline, Week 52 | 
| Change From Baseline in Patient Global Assessment (PGA) of Arthritis of the Index Knee at Week 16 | The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period. | Baseline, Week 16 | 
| Change From Baseline in PGA of Arthritis of the Index Knee at Week 26 | The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period. | Baseline, Week 26 | 
| Change From Baseline in PGA of Arthritis of the Index Knee at Week 52 | The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period. | Baseline, Week 52 | 
| Change From Baseline in Cartilage Volume of the Index Knee at Week 26 | Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI. | Baseline, Week 26 | 
| Change From Baseline in Cartilage Volume of the Index Knee at Week 52 | Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI. | Baseline, Week 52 | 
| Change From Baseline in Cartilage Thickness of the Index Knee at Week 26 | Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI. | Baseline, Week 26 | 
| Change From Baseline in Cartilage Thickness of the Index Knee at Week 52 | Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI. | Baseline, Week 52 | 
| Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 16 | Percentage of participants classified as OMERACT-OARSI responders at Week 16. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation. | Week 16 | 
| Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 26 | Percentage of participants classified as OMERACT-OARSI responders at Week 26. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation. | Week 26 | 
| Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 52 | Percentage of participants classified as OMERACT-OARSI responders at Week 52. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation. | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Synovitis, Knee, Pain