Phase 3
N=226
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 Colchicines Including a 12 Week Extension and a 1 Year Open-label Extension Study.
Acute Gout
Bottom Line
View on ClinicalTrials.gov: NCT01080131 ↗Enrolled (actual)
226
Serious AEs
5.8%
Results posted
Dec 2011
Primary outcome: Primary: Time to First New Flare: Survival Analysis During the 12 Weeks of Study — 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
- Nov 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to First New Flare: Survival Analysis During the 12 Weeks of Study |
NA; NA | — |
| PRIMARY Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose |
22.1; 31.9 | — |
| PRIMARY Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks |
78; 65; 1; 0; 7; 2 | — |
| PRIMARY Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) |
85; 44; 39; 70; 29; 27 | — |
| 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 (VAS) |
25.0; 48.0 | — |
| SECONDARY Time to Complete Resolution of Pain; Survival Analysis |
144.0; NA | — |
| SECONDARY SF 36 Physical Function Score at Week 12 |
81.46; 78.75 | — |
| SECONDARY Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study |
13.4; 36.8 | — |
| SECONDARY Pharmacokinetic Concentrations |
2.16 | — |
| SECONDARY Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) |
58.7; 60.3; 50.8; 52.0; 39.1; 45.0 | — |
| SECONDARY Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) |
57.4; 59.1; 50.7; 53.3; 46.2; 43.8 | — |
| SECONDARY Time to the First New Gout Flare During 24 Weeks |
NA; 146 | — |
| SECONDARY Mean Number of New Gout Flares Per Patient During 24 Weeks |
0.35; 0.80 | — |
| SECONDARY Time to First Intake of Rescue Medication |
NA; 37.5; 32; NA | — |
| SECONDARY Percentage of Participants Who Took Rescue Medication |
43.8; 57.0; 56.0; 41.3 | — |
| SECONDARY Amount of Rescue Medication Taken |
1375.0; 2526.5; 27.2; 60.6; 9.2; 19.3 | — |
| SECONDARY Physician's Global Assessment of Response to Treatment |
43.0; 25.7; 43.0; 35.8; 11.2; 26.6 | — |
| SECONDARY Patient's Global Assessment of Response to Treatment |
36.1; 19.4; 37.0; 32.4; 18.5; 13.9 | — |
| SECONDARY Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint |
47.7; 30.3; 43.9; 46.8; 4.7; 14.7 | — |
| SECONDARY Physician's Assessment of Range of Motion of the Most Affected Joint |
47.7; 28.4; 37.4; 45.9; 13.1; 20.2 | — |
| SECONDARY High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels |
3.84; 6.38; 6.31; 15.85; 3.69; 4.32 | — |
| SECONDARY Patient's Assessment of Gout Pain Intensity in the Most Affected Joint |
30.6; 18.0; 48.1; 45.0; 20.4; 27.0 | — |
| SECONDARY Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme |
66.7; 78.4; 64.0; 78.3 | — |
| SECONDARY Time to First New Flare: Survival Analysis by Treatment Over 72 Weeks |
254.0; 146.0 | — |
| SECONDARY Flare Rate Per Year |
1.18; 2.02 | — |
| SECONDARY Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab |
30.5; 25.0; 44.1; 62.5; 22.0; 12.5 | — |
| SECONDARY Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab |
41.4; 36.8; 32.8; 39.5; 12.1; 21.1 | — |
| SECONDARY Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab |
39.3; 42.1; 39.3; 39.5; 16.1; 18.4 | — |
| SECONDARY Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab |
51.8; 42.1; 37.5; 50.0; 5.4; 5.3 | — |
| SECONDARY Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab |
55.4; 47.4; 26.8; 34.2; 12.5; 15.8 | — |
| SECONDARY Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab |
73.2; 92.1; 26.8; 7.9; 84.5; 94.9 | — |
| SECONDARY High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab |
30.1; 39.4; 10.4; 12.6; 2.8; 3.5 | — |
| SECONDARY Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab |
129.0; 145.9; 45.6; 45.4; 5.7; 5.9 | — |
Summary
The purpose of this 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 CACZ885H2357.
The purpose of the second one year open-label extension study was to confirm the long-term safety and tolerability of canakinumab in patients who had completed the first extension study.
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, or intolerance, or lack of efficacy for non-steroidal anti-inflammatory drugs (NSAID) 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 Criteria
- Completion of the first extension study CACZ885H2357E1. A patient was defined as completing the first extension study if they completed the study up to and including Visit 10).
Exclusion Criteria
-Continuation in this second 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 (NCT01080131). 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.