Osteoarthritis
Conditions
Brief summary
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.
Interventions
BIOLOGICALbotulinum toxin Type A
A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
DRUGNormal Saline
A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 4 | Baseline, 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. |
| Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 8 | Baseline, 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. |
| Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 12 | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Western Ontario and McMaster Universities Arthritis (WOMAC™) Total Index Score | Baseline, Week 8 | 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. |
| Patient Global Impression of Change Score | Week 8 | 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. |
| Change From Baseline in WOMAC Pain Score | Baseline, Week 8 | 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. |
| Change From Baseline in WOMAC Physical Function Score | Baseline, Week 8 | 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. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin Type A A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1. | 61 |
| Placebo A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1. | 60 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other Miscellaneous Reason | 1 | 0 |
Baseline characteristics
| Characteristic | Botulinum Toxin Type A | Placebo | Total |
|---|---|---|---|
| Age, Customized 40 to 64 Years | 30 Participants | 31 Participants | 61 Participants |
| Age, Customized ≥ 65 Years | 31 Participants | 29 Participants | 60 Participants |
| Sex: Female, Male Female | 32 Participants | 30 Participants | 62 Participants |
| Sex: Female, Male Male | 29 Participants | 30 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 61 | 14 / 60 |
| serious Total, serious adverse events | 1 / 61 | 0 / 60 |
Outcome results
Primary
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.
Time frame: Baseline, Week 12
Population: Safety population included all treated participants based on the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 12 | Baseline | 6.4 Score on a scale | Standard Deviation 1.09 |
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 12 | Change from Baseline at Week 12 | -2.2 Score on a scale | Standard Deviation 1.97 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 12 | Baseline | 6.5 Score on a scale | Standard Deviation 1.28 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 12 | Change from Baseline at Week 12 | -2.5 Score on a scale | Standard Deviation 2.24 |
Primary
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.
Time frame: Baseline, Week 4
Population: Safety population included all treated participants based on the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 4 | Baseline | 6.4 Score on a scale | Standard Deviation 1.09 |
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 4 | Change from Baseline at Week 4 | -1.8 Score on a scale | Standard Deviation 1.66 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 4 | Baseline | 6.5 Score on a scale | Standard Deviation 1.28 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 4 | Change from Baseline at Week 4 | -1.8 Score on a scale | Standard Deviation 1.87 |
Primary
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.
Time frame: Baseline, Week 8
Population: Safety population included all treated participants based on the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 8 | Baseline | 6.4 Score on a scale | Standard Deviation 1.09 |
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 8 | Change from Baseline at Week 8 | -2.2 Score on a scale | Standard Deviation 1.96 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 8 | Baseline | 6.5 Score on a scale | Standard Deviation 1.28 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 8 | Change from Baseline at Week 8 | -2.3 Score on a scale | Standard Deviation 2.15 |
Secondary
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.
Time frame: Baseline, Week 8
Population: Safety population included all treated participants based on the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in Western Ontario and McMaster Universities Arthritis (WOMAC™) Total Index Score | Baseline | 104.5 Score on a scale | Standard Deviation 36.53 |
| Botulinum Toxin Type A | Change From Baseline in Western Ontario and McMaster Universities Arthritis (WOMAC™) Total Index Score | Change from Baseline at Week 8 (n=59,59) | -46.5 Score on a scale | Standard Deviation 35.21 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Arthritis (WOMAC™) Total Index Score | Baseline | 107.6 Score on a scale | Standard Deviation 37.44 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Arthritis (WOMAC™) Total Index Score | Change from Baseline at Week 8 (n=59,59) | -43.8 Score on a scale | Standard Deviation 47.25 |
Secondary
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.
Time frame: Baseline, Week 8
Population: Safety population included all treated participants based on the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in WOMAC Pain Score | Baseline | 23.9 Score on a scale | Standard Deviation 6.76 |
| Botulinum Toxin Type A | Change From Baseline in WOMAC Pain Score | Change from Baseline at Week 8 (n=59,59) | -10.7 Score on a scale | Standard Deviation 7.27 |
| Placebo | Change From Baseline in WOMAC Pain Score | Baseline | 24.3 Score on a scale | Standard Deviation 7.01 |
| Placebo | Change From Baseline in WOMAC Pain Score | Change from Baseline at Week 8 (n=59,59) | -11.0 Score on a scale | Standard Deviation 9.75 |
Secondary
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.
Time frame: Baseline, Week 8
Population: Safety population included all treated participants based on the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in WOMAC Physical Function Score | Baseline | 71.0 Score on a scale | Standard Deviation 28.43 |
| Botulinum Toxin Type A | Change From Baseline in WOMAC Physical Function Score | Change from Baseline at Week 8 (n=59,59 ) | -31.7 Score on a scale | Standard Deviation 26.41 |
| Placebo | Change From Baseline in WOMAC Physical Function Score | Baseline | 73.3 Score on a scale | Standard Deviation 29.77 |
| Placebo | Change From Baseline in WOMAC Physical Function Score | Change from Baseline at Week 8 (n=59,59 ) | -28.6 Score on a scale | Standard Deviation 35.26 |
Secondary
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.
Time frame: Week 8
Population: Participants from the Safety population (all treated participants based on the actual treatment received) with data available for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin Type A | Patient Global Impression of Change Score | 1.3 Score on a scale | Standard Deviation 1.28 |
| Placebo | Patient Global Impression of Change Score | 1.0 Score on a scale | Standard Deviation 1.38 |
Post Hoc
Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group
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.
Time frame: Baseline, Weeks 4, 8 and 12
Population: Participants from the Safety population (all treated participants based on the actual treatment received) in a subgroup of patients with nociceptive pain (pain that is caused by nerves that react to injury or damage) at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group | Baseline | 6.4 Score on a scale | Standard Deviation 1.01 |
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group | Change from Baseline at Week 4 | -1.9 Score on a scale | Standard Deviation 1.56 |
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group | Change from Baseline at Week 8 | -2.6 Score on a scale | Standard Deviation 2.01 |
| Botulinum Toxin Type A | Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group | Change from Baseline at Week 12 | -2.6 Score on a scale | Standard Deviation 1.79 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group | Change from Baseline at Week 12 | -2.0 Score on a scale | Standard Deviation 2.27 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group | Baseline | 6.4 Score on a scale | Standard Deviation 1.35 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group | Change from Baseline at Week 8 | -1.8 Score on a scale | Standard Deviation 2.01 |
| Placebo | Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group | Change from Baseline at Week 4 | -1.5 Score on a scale | Standard Deviation 1.58 |
Post Hoc
Change From Baseline in WOMAC Pain Score in the Nociceptive Pain Group
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.
Time frame: Baseline, Week 8
Population: Participants from the Safety population (all treated participants based on the actual treatment received) in a subgroup of patients with nociceptive pain (pain that is caused by nerves that react to injury or damage) at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in WOMAC Pain Score in the Nociceptive Pain Group | Baseline | 22.7 Score on a scale | Standard Deviation 5.95 |
| Botulinum Toxin Type A | Change From Baseline in WOMAC Pain Score in the Nociceptive Pain Group | Change from Baseline at Week 8 (n=35,31) | -11.0 Score on a scale | Standard Deviation 7.09 |
| Placebo | Change From Baseline in WOMAC Pain Score in the Nociceptive Pain Group | Baseline | 22.9 Score on a scale | Standard Deviation 6.98 |
| Placebo | Change From Baseline in WOMAC Pain Score in the Nociceptive Pain Group | Change from Baseline at Week 8 (n=35,31) | -7.5 Score on a scale | Standard Deviation 9 |