Arthritis, Gouty
Conditions
Keywords
Arthritis Gouty, ACZ885, IL1B protein, Pain
Brief summary
This is an exploratory proof-of-concept study to evaluate the safety and efficacy of canakinumab (ACZ885) for inflammation and pain associated with acute gouty arthritis.
Interventions
BIOLOGICALcanakinumab
10 mg/kg intravenous infusion 250 mL over 2 hours.
DRUGdexamethasone
12 mg intravenous infusion 50 mL over 30 minutes.
5% glucose in water intravenous infusion.
OTHERplacebo matching dexamethasone
Placebo intravenous infusion.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* score over 50 on the 0-100 VAS pain scale * acute, confirmed gout flare for no longer than 3 days
Exclusion criteria
* Treatment with biological anti-tumor necrosis factor (anti-TNF) within the past 3 months * Anti-inflammatory medication for the treatment of acute gout within the previous 24 hours * Pregnant or breastfeeding women * Major surgery with high infection risk * History of severe allergy to food or drugs * History or risk of tuberculosis * Active infection Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Improvement in Gout at 72 Hours Post-dose Using a Likert Scale | 72 hours | 72 hours following treatment, patients were asked the question: How would you rate the improvement in your gout since receiving the study medication? Patients rated their improvement on the Likert 5-point scale: 1=Excellent, 2=Good, 3=Acceptable,4=Slight and 5=Poor. Improvement was assessed by determining patients who scored a good or excellent response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recurrence of the Symptoms of Acute Gout (if Applicable) During Treatment Period | 4 months | Time to recurrence is defined as from the point of improvement (good to excellent on Likert scale) to recurrence. |
| Time to Walk Independently (if Applicable) During Treatment Period | 4 months | — |
| Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study | 4 months | Additional safety information can be found in the Adverse Event section. |
| Change in C-reactive Protein (CRP) From Baseline at Month 4 | Baseline, Month 4 | Blood was collected at Baseline and Month 4 for CRP to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement. |
| Non-inferiority of a Single Dose of Canakinumab Compared to Dexamethasone During Treatment Period | 72 hours | — |
| ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Baseline, Days 0.25, 1, 3, 6, 20, 34, 55 and 119 | Blood was collected for ACZ885 (canakinumab) levels at baseline and Days 0.25, 1, 3, 6, 20, 34, 55 and 119. Serum was analyzed by means of a competitive Enzyme linked immunosorbant assay (ELISA). |
| Change From Baseline in Pain Using a Visual Analog Scale at Month 4 | Baseline, Month 4 | Patients rated their pain on a 100 millimeter (mm) visual analog scale, ranging from no pain (0) to unbearable pain (100). A negative change from baseline indicates improvement. |
| Number of Patients Who Took Rescue Medication | 4 months | Patients who did not improve by 72 hours post-dose (i.e. patients who show a pain Visual Analog (VAS) decrease of less than 50 % from baseline (Day 1, pre-dose) would have been treated with rescue medication of methylprednisolone 80 mg intravenous or intramuscular once at the discretion of the clinical investigator. |
| Change in Serum Amyloid A Protein (SAA) From Baseline at Month 4 | Baseline, Month 4 | Blood was collected at Baseline and Month 4 for SAA to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement. |
Countries
Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab Canakinumab 10 mg/kg intravenous infusion and placebo matching dexamethasone intravenous infusion on Day 1. | 3 |
| Dexamethasone Dexamethasone 12 mg intravenous infusion and placebo matching canakinumab on Day 1. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Canakinumab | Dexamethasone | Total |
|---|---|---|---|
| Age Continuous | 46.7 years STANDARD_DEVIATION 10.97 | 46.0 years STANDARD_DEVIATION 3.46 | 46.3 years STANDARD_DEVIATION 7.28 |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 |
Outcome results
Primary
Percentage of Participants With Improvement in Gout at 72 Hours Post-dose Using a Likert Scale
72 hours following treatment, patients were asked the question: How would you rate the improvement in your gout since receiving the study medication? Patients rated their improvement on the Likert 5-point scale: 1=Excellent, 2=Good, 3=Acceptable,4=Slight and 5=Poor. Improvement was assessed by determining patients who scored a good or excellent response.
Time frame: 72 hours
Population: Pharmacodynamic set included all randomized subjects with evaluable (or complete) pharmacodynamic parameter data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Percentage of Participants With Improvement in Gout at 72 Hours Post-dose Using a Likert Scale | 100 Percentage of participants |
| Dexamethasone | Percentage of Participants With Improvement in Gout at 72 Hours Post-dose Using a Likert Scale | 100 Percentage of participants |
Secondary
ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period
Blood was collected for ACZ885 (canakinumab) levels at baseline and Days 0.25, 1, 3, 6, 20, 34, 55 and 119. Serum was analyzed by means of a competitive Enzyme linked immunosorbant assay (ELISA).
Time frame: Baseline, Days 0.25, 1, 3, 6, 20, 34, 55 and 119
Population: Pharmacodynamic set included all randomized subjects with evaluable (or complete) pharmacodynamic parameter data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Baseline | 0.0 μg/mL | Standard Deviation 0 |
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Day 0.25 | 221.5 μg/mL | Standard Deviation 143.58 |
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Day 1 (n=2) | 276.5 μg/mL | Standard Deviation 26.163 |
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Day 6 | 136.6 μg/mL | — |
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Day 3 (n=1) | 92.3 μg/mL | — |
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Day 20 | 72.37 μg/mL | Standard Deviation 11.154 |
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Day 34 | 52.87 μg/mL | Standard Deviation 13.194 |
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Day 55 | 31.67 μg/mL | Standard Deviation 8.4884 |
| Canakinumab | ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period | Day 119 | 7.643 μg/mL | Standard Deviation 4.6151 |
Secondary
Change From Baseline in Pain Using a Visual Analog Scale at Month 4
Patients rated their pain on a 100 millimeter (mm) visual analog scale, ranging from no pain (0) to unbearable pain (100). A negative change from baseline indicates improvement.
Time frame: Baseline, Month 4
Population: Pharmacodynamic set included all randomized subjects with evaluable (or complete) pharmacodynamic parameter data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab | Change From Baseline in Pain Using a Visual Analog Scale at Month 4 | -62.0 Score on a scale | Standard Deviation 3.61 |
| Dexamethasone | Change From Baseline in Pain Using a Visual Analog Scale at Month 4 | -65.7 Score on a scale | Standard Deviation 17.62 |
Secondary
Change in C-reactive Protein (CRP) From Baseline at Month 4
Blood was collected at Baseline and Month 4 for CRP to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement.
Time frame: Baseline, Month 4
Population: Pharmacodynamic set included all randomized patients with evaluable (or complete) pharmacodynamic parameter data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab | Change in C-reactive Protein (CRP) From Baseline at Month 4 | -22.23 mg/L | Standard Deviation 16.822 |
| Dexamethasone | Change in C-reactive Protein (CRP) From Baseline at Month 4 | -30.30 mg/L | Standard Deviation 51.963 |
Secondary
Change in Serum Amyloid A Protein (SAA) From Baseline at Month 4
Blood was collected at Baseline and Month 4 for SAA to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement.
Time frame: Baseline, Month 4
Population: Pharmacodynamic set included all randomized patients with evaluable (or complete) pharmacodynamic parameter data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab | Change in Serum Amyloid A Protein (SAA) From Baseline at Month 4 | -579.980 mg/L | Standard Deviation 563.7449 |
| Dexamethasone | Change in Serum Amyloid A Protein (SAA) From Baseline at Month 4 | -260.327 mg/L | Standard Deviation 463.86 |
Secondary
Non-inferiority of a Single Dose of Canakinumab Compared to Dexamethasone During Treatment Period
Time frame: 72 hours
Population: Since the study only recruited 6 subjects this analysis was not done.
Secondary
Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study
Additional safety information can be found in the Adverse Event section.
Time frame: 4 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study | Discontinuation from treatment | 0 Participants |
| Canakinumab | Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study | Death | 0 Participants |
| Canakinumab | Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study | Serious Adverse Event | 0 Participants |
| Dexamethasone | Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study | Discontinuation from treatment | 0 Participants |
| Dexamethasone | Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study | Death | 0 Participants |
| Dexamethasone | Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study | Serious Adverse Event | 1 Participants |
Secondary
Number of Patients Who Took Rescue Medication
Patients who did not improve by 72 hours post-dose (i.e. patients who show a pain Visual Analog (VAS) decrease of less than 50 % from baseline (Day 1, pre-dose) would have been treated with rescue medication of methylprednisolone 80 mg intravenous or intramuscular once at the discretion of the clinical investigator.
Time frame: 4 months
Population: All participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Number of Patients Who Took Rescue Medication | 0 Participants |
| Dexamethasone | Number of Patients Who Took Rescue Medication | 0 Participants |
Secondary
Time to Recurrence of the Symptoms of Acute Gout (if Applicable) During Treatment Period
Time to recurrence is defined as from the point of improvement (good to excellent on Likert scale) to recurrence.
Time frame: 4 months
Population: Since the study recruited only 6 subjects this analysis was not done.
Secondary
Time to Walk Independently (if Applicable) During Treatment Period
Time frame: 4 months
Population: Since the study recruited only 6 subjects this analysis was not done.