TriangleNCT01029652 · 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 Colchicine Including a 12 Weeks Extension and an Open-label 48 Weeks 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 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.
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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
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)
Time to Complete Resolution of Pain
Percentage of Participants With Complete Resolution of Pain
Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks
Mean Number of New Gout Flares Per Patient
SF36 Physical Function Score at Week 12
Time to First New Flare
Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study
Time to First Intake of Rescue Medication After the Last Post Baseline Flare.
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension
Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale)
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS)
Amount of Rescue Medication Taken
Percentage of Participants Who Took Rescue Medication
High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall
Physician's Global Assessment of Response to Treatment
Patient's Global Assessment of Response to Treatment
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall)
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
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale)
Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall)
Flare Rate Per Year
High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab
Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall)
Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab
Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale)
Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab
Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab
Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab
Physician's Assessment of Erythema for Patients Re-treated 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, 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.
- 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
- Patients received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Patients could receive re-dose of study drug on demand upon occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after previous dose. Patients completing 12 weeks core study were allowed to continue treatment in another 12-week extension for any new gout flare on demand with same treatment as assigned in core study. After completing the first extension, patients were offered to enter second extension study, whereby all patients were treated open-label "on demand" with canakinumab 150 mg sc upon new flare for 1 year for a total duration of 18 months following randomization in core study. Patients completing first 12 weeks extension study were allowed to continue to be treated in another single-arm, open-label 48 weeks extension when all patients from both treatment arms received canakinumab on demand
- intervention Names
- Drug: Canakinumab 150 mg
- Drug: Placebo to triamcinolone acetonide
- label
- Canakinumab 150 mg
- type
- EXPERIMENTAL
- description
- Patients received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Patients 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. Patients completing the 12 weeks core study were allowed to continue to be treated in another 12 weeks extension study for any new gout flare on demand with the same treatment as assigned in the core study. Patients under this arm who agreed to continue to 2nd extension period of 12 months, were switched to canakinumab 150 mg sc for any new gout flare during this period Triamcinolone acetonide was not to be administered in the 48-week session.
- 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
- 230
- 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
- time Frame
- 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 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 (0-100mm VAS)
- time Frame
- 72 hours post-dose (randomization)
- description
- This was the primary endpoint of both extension studies. 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. 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 (AE), Death and Serious Adverse Events (24 Weeks Overall)
- time Frame
- 24 weeks overall
- description
- This was the primary endpoint of both extension studies. 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. 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 (AE), Death and Serious Adverse Events (72 Weeks Overall)
- time Frame
- 72 weeks overall
- secondary Outcomes
- description
- The Kaplan-Meier estimates of the time to at least a 50% reduction in self-assessed pain intensity in the joint most affected at baseline was determined along with the 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 (0-100mm VAS)
- time Frame
- From baseline to 7 days post dose (randomization)
- description
- Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Complete Resolution of Pain is defined as no pain (None) on the Likert Scale. 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. The Kaplan-Meier estimates of time to complete resolution of self-assessed pain intensity in the joint most affected and their confidence intervals were determined.
- measure
- Time to Complete Resolution of Pain
- time Frame
- 7 days post-dose (randomization)
- description
- Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). 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. Complete Resolution of Pain is defined as no pain (None) on the Likert Scale. The Kaplan-Meier estimates of cumulative event rate = percentage of participants with event up to the end of the time interval.
- measure
- Percentage of Participants With Complete Resolution of Pain
- time Frame
- 7 days post-dose (randomization)
- 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. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
- measure
- Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks
- time Frame
- 12 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. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
- measure
- Mean Number of New Gout Flares Per Patient
- time Frame
- 12 weeks
- description
- The SF-36 measures the impact of disease on overall quality of life (QoL). This 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 an 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. A negative change score indicates improvement. An ANCOVA model was used with treatment group and baseline SF-36 physical function subscore as covariates.
- measure
- SF36 Physical Function Score at Week 12
- time Frame
- Week 12
- description
- Kaplan-Meier (KM) estimates of time to first new flare and confidence intervals were determined. 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 the flare has resolved completely.
- measure
- Time to First New Flare
- time Frame
- 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. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
- measure
- Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study
- time Frame
- 24 weeks
- description
- The Kaplan-Meier estimates of medians and 95% confidence intervals were used to calculate the endpoint.
- measure
- Time to First Intake of Rescue Medication After the Last Post Baseline Flare.
- time Frame
- 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
- 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). 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
- Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension
- time Frame
- 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
- description
- Maximum severity is the maximum Likert score recorded after the start of the flare. Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme).
- measure
- Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale)
- time Frame
- Last post-baseline flare (during 24 weeks overall)
- 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 prednisolon 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
- 7 days last post-baseline flare (during 24 weeks)
Full study description
- brief 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.
- detailed Description
- Masking: Core: Double Blind (Subject, Investigator) Extension 1: Double Blind (Subject, Investigator) Extension 2: Open-label, terminated
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
- 24122883
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- a third open-label extension (combined for both studies) up to a maximum of 36 months where all patients were treated with ILARIS upon a new flare. In Study 1 (NCT01029652), patients were randomized to receive ILARIS 150 mg subcutaneous (N = 115) or triamcinolone acetonide 40 mg intramuscular (N = 115) at baseline and thereafter
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Preserved source evidence · Not medical advice