TriangleNCT01080131 · CITED IN SOURCE DOCUMENTS
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.
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2014-01-30
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.
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Time to First New Flare: Survival Analysis During the 12 Weeks of Study
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)
Time to Complete Resolution of Pain; Survival Analysis
SF 36 Physical Function Score at Week 12
Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose
Pharmacokinetic Concentrations
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS)
Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS)
Time to the First New Gout Flare During 24 Weeks
Mean Number of New Gout Flares Per Patient During 24 Weeks
Time to First Intake of Rescue Medication
Percentage of Participants Who Took Rescue Medication
Amount of Rescue Medication Taken
Physician's Global Assessment of Response to Treatment
Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks
Patient's Global Assessment of Response to Treatment
Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint
Physician's Assessment of Range of Motion of the Most Affected Joint
Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall)
High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint
Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme
Time to First New Flare: Survival Analysis by Treatment Over 72 Weeks
Flare Rate Per Year
Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab
Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab
Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab
Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab
Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab
Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab
High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab
Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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.
- healthy Volunteers
- false
- maximum Age
- 85 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year, for a total duration of 18 months.
- intervention Names
- Drug: Canakinumab 150 mg
- Drug: Placebo to triamcinolone acetonide
- label
- Canakinumab 150 mg
- type
- EXPERIMENTAL
- description
- Participants received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year. Triamcinolone acetonide was not to be administered in the second extension study.
- intervention Names
- Drug: Triamcinolone acetonide 40 mg
- Drug: Placebo to canakinumab
- label
- Triamcinolone acetonide 40 mg
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Canakinumab 150 mg
- description
- Canakinumab 150 mg was supplied in 6 mL glass vials each containing nominally 150 mg canakinumab (plus 20% overfill).
- name
- Canakinumab 150 mg
- type
- DRUG
- arm Group Labels
- Triamcinolone acetonide 40 mg
- description
- Triamcinolone acetonide 40 mg was supplied as a suspension.
- name
- Triamcinolone acetonide 40 mg
- type
- DRUG
- arm Group Labels
- Triamcinolone acetonide 40 mg
- description
- Placebo to canakinumab was supplied in 6 mL glass vials containing placebo powder as a lyophilized cake.
- name
- Placebo to canakinumab
- type
- DRUG
- arm Group Labels
- Canakinumab 150 mg
- description
- Placebo triamcinolone acetonide was supplied as a lipid emulsion similar in appearance to triamcinolone acetonide.
- name
- Placebo to triamcinolone acetonide
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 226
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1). Patients met definition of new flare if they had: •Flare in joint, not a previously affected joint (at baseline or during study) •Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: • Increasing/renewed gout pain in an affected joint before flare has resolved completely.
- measure
- Time to First New Flare: Survival Analysis During the 12 Weeks of Study
- time Frame
- Baseline to 12 weeks
- description
- Patients scored their pain intensity in the joint most affected at Baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), at 72 hours post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The analysis of covariance (ANCOVA) analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
- measure
- Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose
- time Frame
- 72 hours post-dose (randomization)
- description
- This was primary endpoint of extension study 1. Adverse event is defined as any unfavorable and unintended diagnosis, symptom sign including an abnormal laboratory finding, syndrome or disease which either occurs during the study, having been absent at baseline, or, if present at baseline, appears to worsen. A serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
- measure
- Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks
- time Frame
- During 24 weeks overall
- description
- This was the primary endpoint of extension study 2. An adverse event was defined as any unfavorable and unintended diagnosis, symptom sign including an abnormal laboratory finding, syndrome or disease which either occurs during the study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
- measure
- Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall)
- time Frame
- 72 weeks
- secondary Outcomes
- description
- Kaplan-Meier estimates of the time to at least a 50% reduction in self-assessed pain intensity in the joint most affected at Baseline and the confidence intervals were determined along with 95% confidence interval. Patients scored their pain intensity on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose.
- measure
- 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)
- time Frame
- Baseline to 7 days post-dose (randomization)
- description
- Kaplan-Meier estimates of the time to complete resolution of self-assessed pain intensity in the joint most affected and the confidence interval was determined. Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Pain was scored at Baseline; 6 and 12 hours; 1, 2, 3, 4, 5, 6, and 7 days post-dose.
- measure
- Time to Complete Resolution of Pain; Survival Analysis
- time Frame
- Baseline to 7 days post-dose (randomization)
- description
- SF-36 measures impact of disease on overall quality of life (QoL). 36-item survey has 8 subscales that can be aggregated into physical and mental component summary scores. Scores are standardized with the use of norm-based methods based on assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL. Analysis of covariance (ANCOVA) model was used with treatment group and baseline SF-36 physical function subscore as covariates.
- measure
- SF 36 Physical Function Score at Week 12
- time Frame
- Week 12
- description
- The percentage of participants who experienced at least 1 new gout flare during the 12 week study treatment period.
- measure
- Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study
- time Frame
- Baseline to Week 12
- description
- Canakinumab concentration was analyzed in serum by means of a competitive Enzyme-linked immunosorbent assay (ELISA) assay with a lower limit of quantification (LOQ) at 100 ng/mL.
- measure
- Pharmacokinetic Concentrations
- time Frame
- 12 weeks post-dose
- description
- Patients scored their pain intensity in the joint most affected at Baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), from 6 hours to 7 days post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
- measure
- Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS)
- time Frame
- 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose (randomization)
- description
- Patient's assessment of gout pain intensity in the most affected joint (on a 0-100 mm VAS) for the last post-baseline flare, ranging from no pain (0) to unbearable pain (100), was summarized up to 7 days after receiving a re-dose of study drug by time point. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The covariance analysis included treatment group, Baseline VAS score at that flare, and body mass index (BMI) at Baseline as covariates.
- measure
- Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS)
- time Frame
- 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose for last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
- description
- Kaplan-Meier (KM) estimates of the time to first new flare and confidence intervals were determined. Participants met the definition of a new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Participants did not meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely.
- measure
- Time to the First New Gout Flare During 24 Weeks
- time Frame
- From randomization to the end of the first extension period (24 weeks).
- description
- Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint(at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Participants did not meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely.
- measure
- Mean Number of New Gout Flares Per Patient During 24 Weeks
- time Frame
- 24 weeks
- description
- Participants who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows: * Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed. * If they had insufficient pain relief, participants were allowed to take a maximum of 30 mg of oral prednisolone as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare. Use of these treatments during the first 7 days of a gout flare was recorded as rescue medication. Kaplan-Meier estimates of the time to first intake of rescue medication, in hours, and the confidence interval were determined for the flare experienced at study entry (Baseline flare) and the last new flare (last post-baseline flare) that occurred up until the end of the first extension period (24 weeks).
- measure
- Time to First Intake of Rescue Medication
- time Frame
- For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
- description
- Participants who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows: * Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed. * If they had insufficient pain relief, participants were allowed to take a maximum of 30 mg of oral prednisolone as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare. Use of these treatments during the first 7 days of a gout flare was recorded as rescue medication.
- measure
- Percentage of Participants Who Took Rescue Medication
- time Frame
- For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
- description
- Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows: * Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed. * If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolone as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare.
- measure
- Amount of Rescue Medication Taken
- time Frame
- For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
Full study description
- brief 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.
Source references
- references
- citation
- Chakraborty A, Van LM, Skerjanec A, Floch D, Klein UR, Krammer G, Sunkara G, Howard D. Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis. J Clin Pharmacol. 2013 Dec;53(12):1240-51. doi: 10.1002/jcph.162. Epub 2013 Sep 30.
- pmid
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Source notices and limitations
Discovery and provenance
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- er treated upon a new flare. Two patients randomized to canakinumab were not included in the analysis as they did not receive any study medication. In Study 2 (NCT01080131), patients were randomized to receive ILARIS 150 mg subcutaneous (N =112) or triamcinolone acetonide 40 mg intramuscular (N =114) at baseline and thereafter tr
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Preserved source evidence · Not medical advice