Phase 3
N=230
Canakinumab in the Treatment of Acute Gout Flares and Prevention of New Flares in Patients Unable to Use Non-steroidal Anti-inflammatory Drugs (NSAIDs) and/or Colchicine Including a 12 Weeks Extension and an Open-label 48 Weeks Extension Study
Acute Gout
Bottom Line
View on ClinicalTrials.gov: NCT01029652 ↗Enrolled (actual)
230
Serious AEs
10.4%
Results posted
Nov 2011
Primary outcome: Primary: Time to First New Flare — NA; NA Days
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Canakinumab 150 mg (Drug); Triamcinolone acetonide 40 mg (Drug); Placebo to canakinumab (Drug); Placebo to triamcinolone acetonide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Oct 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to First New Flare |
NA; 119 | — |
| PRIMARY Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) |
28.1; 39.5 | — |
| PRIMARY Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) |
71; 56; 0; 1; 11; 6 | — |
| PRIMARY Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) |
76; 41; 38; 60; 20; 19 | — |
| SECONDARY Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) |
48.0; 72.0 | — |
| SECONDARY Time to Complete Resolution of Pain |
NA; NA | — |
| SECONDARY Percentage of Participants With Complete Resolution of Pain |
34.5; 31.3 | — |
| SECONDARY Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks |
18.6; 34.8 | — |
| SECONDARY Mean Number of New Gout Flares Per Patient |
0.21; 0.53 | — |
| SECONDARY SF36 Physical Function Score at Week 12 |
71.76; 71.48 | — |
| SECONDARY Time to First New Flare |
NA; 119 | — |
| SECONDARY Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study |
0.40; 0.87 | — |
| SECONDARY Time to First Intake of Rescue Medication After the Last Post Baseline Flare. |
NA; NA | — |
| SECONDARY Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension |
34.6; 44.9 | — |
| SECONDARY Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) |
0.0; 0.0; 0.0; 2.3; 14.3; 16.3 | — |
| SECONDARY Amount of Rescue Medication Taken |
1931.4; 2058.1; 7.7; 46.0; 4.1; 21.6 | — |
| SECONDARY Percentage of Participants Who Took Rescue Medication |
31.0; 52.2; 48.6; 44.2 | — |
| SECONDARY High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall |
4.50; 7.08; 6.77; 17.00; 5.18; 7.18 | — |
| SECONDARY Physician's Global Assessment of Response to Treatment |
16.8; 15.5; 47.8; 30.0; 26.5; 32.7 | — |
| SECONDARY Patient's Global Assessment of Response to Treatment |
12.4; 12.6; 38.9; 28.8; 37.2; 30.6 | — |
| SECONDARY Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint |
33.6; 26.4; 56.6; 51.8; 8.0; 17.3 | — |
| SECONDARY Physician's Assessment of Range of Motion of the Most Affected Joint |
25.7; 31.5; 50.4; 29.7; 21.2; 27.0 | — |
| SECONDARY Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) |
32.7; 28.0; 48.2; 41.1; 16.4; 16.8 | — |
| SECONDARY Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall) |
222.0; 119.0 | — |
| SECONDARY Flare Rate Per Year |
1.16; 2.81 | — |
| SECONDARY High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab |
28.9; 26.0; 10.6; 7.0; 3.3; 3.2 | — |
| SECONDARY Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab |
151.4; 86.5; 42.5; 26.9; 5.4; 4.9 | — |
| SECONDARY Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab |
21.3; 22.9; 41.0; 57.1; 31.1; 17.1 | — |
| SECONDARY Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) |
19.7; 20.5; 30.0; 61.5; 45.5; 15.4 | — |
| SECONDARY Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab |
15.0; 19.4; 26.7; 44.4; 50.0; 27.8 | — |
| SECONDARY Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab |
27.9; 28.6; 54.1; 68.6; 16.4; 2.9 | — |
| SECONDARY Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab |
29.5; 42.9; 42.6; 48.6; 24.6; 8.6 | — |
| SECONDARY Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab |
82.0; 80.0; 18.0; 20.0; 95.5; 94.4 | — |
Summary
The purpose of the 12-week core study was to demonstrate that canakinumab given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares in patients with frequent flares of gout for whom non-steroidal anti-inflammatory drugs (NSAIDs) and/ or colchicine are contraindicated, not tolerated, or ineffective. The efficacy of canakinumab was compared to the corticosteroid triamcinolone acetonide.
The purpose of the first 12-week extension study was to collect additional safety, tolerability and efficacy data in patients who have completed the core study CACZ885H2356.
The purpose of the second 48 week open-label extension study was to collect additional long-term safety and tolerability data in patients who have completed the first extension study CACZ885H2356E1.
Eligibility Criteria
Core Study:
Inclusion criteria
- Meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout
- Onset of current acute gout flare within 5 days prior to study entry
- Baseline pain intensity ≥ 50 mm on the 0-100 mm visual analog scale (VAS)
- History of ≥ 3 gout flares within the 12 months prior to study entry
- Contraindication, intolerance, or lack of efficacy for non-steroidal anti-inflammatory drugs (NSAIDs) and/or colchicine
Exclusion criteria
- Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis
- Presence of severe renal function impairment
- Use of specified pain relief medications or biologics ( corticosteroids, narcotics, paracetamol/acetominophen, ibuprofen, colchicine, IL-blocker, and tumor necrosis factor inhibitor) within specified periods prior to study entry
- Live vaccinations within 3 months prior to randomization
- Requirement for administration of antibiotics against latent tuberculosis (TB)
- Refractory heart failure (Stage D)
- Unstable cardiac arrhythmias or unstable symptomatic coronary ischemia
- Any active or recurrent bacterial, fungal, or viral infection
Extension Study 1:
Inclusion Completion of the Core study. A patient was defined as completing the core study if they completed the study up to and including visit 7.
Exclusion
- Continuation in this extension study was considered inappropriate by the treating physician.
Extension Study 2:
Inclusion Completed of the first extension study CACZ885H2356E1. A patient was defined as completing the first extension study if they completed the study up to and including Visit 10).
Exclusion
-Continuation in this extension study was considered inappropriate by the treating physician
Other protocol-defined inclusion-exclusion criteria applied to the core and extension studies.
Data sourced from ClinicalTrials.gov (NCT01029652). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.