Safety and Efficacy Study of Botulinum Toxin Type A as Treatment for Osteoarthritis Knee Pain

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of a single intra-articular (IA) injection of botulinum toxin Type A compared with placebo as treatment for osteoarthritis (OA) knee pain.

Conditions
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Osteoarthritis

Intervention / Treatment
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* Biological: botulinum toxin Type A
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Painful osteoarthritis in the study knee Able to walk without assistive walking devices, able to perform usual daily activities, and agree to maintain similar activity level throughout the study Exclusion Criteria: Chronic pain conditions other than knee osteoarthritis Presence of bursitis, meniscus tear, ligament tear, or significant injury to the study knee within 1 year Surgery to the study knee within 24 weeks Treatment with hyaluronic acid in the study knee within 24 weeks Treatment with corticosteroids in the study knee within 12 weeks Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis Previous treatment with botulinum toxin of any serotype for any reason

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: botulinum toxin Type A<br>A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1. | Biological: botulinum toxin Type A<br>* A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.<br>* Other names: BOTOX®;|
| Placebo Comparator: Placebo<br>A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1. | Drug: Normal Saline<br>* A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 4 | The patient rated their daily worst pain intensity in the study knee using an 11-point scale where: 0=no pain to 10=worst pain possible. The daily scores over the previous 14-day period were averaged. A negative change from Baseline indicated improvement. | Baseline, Week 4 | 
| Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 8 | The patient rated their daily worst pain intensity in the study knee using an 11-point scale where: 0=no pain to 10=worst pain possible. The daily scores over the previous 14-day period were averaged. A negative change from Baseline indicated improvement. | Baseline, Week 8 | 
| Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 12 | The patient rated their daily worst pain intensity in the study knee using an 11-point scale where: 0=no pain to 10=worst pain possible. The daily scores over the previous 14-day period were averaged. A negative change from Baseline indicated improvement. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Western Ontario and McMaster Universities Arthritis (WOMAC™) Total Index Score | The WOMAC Total Index Score consisted of 24 components rated on a scale of 0 to 10. The Total Index Score included the WOMAC Pain Score (5 questions about pain where: 0=no pain to 10=extreme pain), the WOMAC Physical Function score (17 questions about the difficulty of daily activities where: 0=no difficulty to 10=extreme difficulty) and the WOMAC Stiffness Score (2 questions about stiffness where: 0=no stiffness to 10=extreme stiffness) for a total possible Index Score of 0 (best) to 240 (worst). A negative change from Baseline indicated improvement. | Baseline, Week 8 | 
| Change From Baseline in WOMAC Pain Score | The WOMAC Pain Score included 5 questions about pain where: 0=no pain to 10=extreme pain for a total possible score of 0 (best) to 50 (worst). A negative change from Baseline indicated improvement. | Baseline, Week 8 | 
| Change From Baseline in WOMAC Physical Function Score | The WOMAC Physical Function Score included 17 questions about the difficulty of daily activities where: 0=no difficulty to 10=extreme difficulty for a total possible score of 0 (best) to 170 (worst). A negative change from Baseline indicated improvement. | Baseline, Week 8 | 
| Patient Global Impression of Change Score | The participants rated the change in their health status since enrollment using a 7-point scale where: +3=very much improved, +2=much improved, +1=minimally improved, 0=no change, -1=minimally worse, -2=much worse and -3=very much worse. Negative scores indicated worsening and positive scores indicated improvement. | Week 8 |