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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01029652




Registration number
NCT01029652
Ethics application status
Date submitted
9/12/2009
Date registered
10/12/2009
Date last updated
30/01/2014

Titles & IDs
Public title
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
Scientific title
A 12 Weeks Randomized, Controlled Core Study of ACZ885 (Canakinumab) on the Treatment and Prevention of Gout Flares in Patients With Frequent Flares for Whom NSAIDs and/or Colchicine Are Contraindicated, Not Tolerated or Ineffective, Including a 12-week Double-blind Extension Study and an Open-label 48 Week Extension Study
Secondary ID [1] 0 0
2009-015018-23
Secondary ID [2] 0 0
CACZ885H2356
Universal Trial Number (UTN)
Trial acronym
ß-RELIEVED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Gout 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Canakinumab 150 mg
Treatment: Drugs - Triamcinolone acetonide 40 mg
Treatment: Drugs - Placebo to canakinumab
Treatment: Drugs - Placebo to triamcinolone acetonide

Experimental: Canakinumab 150 mg - 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

Active Comparator: Triamcinolone acetonide 40 mg - 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.


Treatment: Drugs: Canakinumab 150 mg
Canakinumab 150 mg was supplied in 6 mL glass vials each containing nominally 150 mg canakinumab (plus 20% overfill).

Treatment: Drugs: Triamcinolone acetonide 40 mg
Triamcinolone acetonide 40 mg was supplied as a suspension.

Treatment: Drugs: Placebo to canakinumab
Placebo to canakinumab was supplied in 6 mL glass vials containing placebo powder as a lyophilized cake.

Treatment: Drugs: Placebo to triamcinolone acetonide
Placebo triamcinolone acetonide was supplied as a lipid emulsion similar in appearance to triamcinolone acetonide.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to First New Flare - 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.
Timepoint [1] 0 0
12 weeks
Primary outcome [2] 0 0
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) - 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.
Timepoint [2] 0 0
72 hours post-dose (randomization)
Primary outcome [3] 0 0
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) - 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.
Timepoint [3] 0 0
24 weeks overall
Primary outcome [4] 0 0
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) - 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.
Timepoint [4] 0 0
72 weeks overall
Secondary outcome [1] 0 0
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) - 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.
Timepoint [1] 0 0
From baseline to 7 days post dose (randomization)
Secondary outcome [2] 0 0
Time to Complete Resolution of Pain - 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.
Timepoint [2] 0 0
7 days post-dose (randomization)
Secondary outcome [3] 0 0
Percentage of Participants With Complete Resolution of Pain - 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.
Timepoint [3] 0 0
7 days post-dose (randomization)
Secondary outcome [4] 0 0
Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks - 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.
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Mean Number of New Gout Flares Per Patient - 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.
Timepoint [5] 0 0
12 weeks
Secondary outcome [6] 0 0
SF36 Physical Function Score at Week 12 - 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.
Timepoint [6] 0 0
Week 12
Secondary outcome [7] 0 0
Time to First New Flare - 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.
Timepoint [7] 0 0
24 weeks
Secondary outcome [8] 0 0
Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study - 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.
Timepoint [8] 0 0
24 weeks
Secondary outcome [9] 0 0
Time to First Intake of Rescue Medication After the Last Post Baseline Flare. - The Kaplan-Meier estimates of medians and 95% confidence intervals were used to calculate the endpoint.
Timepoint [9] 0 0
72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Secondary outcome [10] 0 0
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension - 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.
Timepoint [10] 0 0
72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Secondary outcome [11] 0 0
Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) - 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).
Timepoint [11] 0 0
Last post-baseline flare (during 24 weeks overall)
Secondary outcome [12] 0 0
Amount of Rescue Medication Taken - 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.
Timepoint [12] 0 0
7 days last post-baseline flare (during 24 weeks)
Secondary outcome [13] 0 0
Percentage of Participants Who Took Rescue Medication - Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments. Permitted rescue medications included acetaminophen 500 mg and/ or codeine 30 mg as needed. If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolone as needed per day for 2 days followed by up to 20 mg of prednisolone as needed per day for 3 subsequent days within 7 days after randomization or after re-dose/injection administration.
Timepoint [13] 0 0
during 12 weeks core, 24 weeks overall
Secondary outcome [14] 0 0
High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall - High sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The analysis included treatment group, log-transformed protein level at baseline, and body mass index (BMI) at baseline as covariates.
Timepoint [14] 0 0
72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Secondary outcome [15] 0 0
Physician's Global Assessment of Response to Treatment - The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's assessments (pain intensity [Visual Analog Scale and Likert scale] and patient's global assessment of response to treatment).
Timepoint [15] 0 0
72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Secondary outcome [16] 0 0
Patient's Global Assessment of Response to Treatment - Patients made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. Percentage of participants in each category for both core and extension periods were measured.
Timepoint [16] 0 0
72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Secondary outcome [17] 0 0
Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint - The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that "there is pain", patient states "there is pain and winces", and patient states "there is pain, winces, and withdraws" on palpation or passive movement of the affected study joint; Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; and Erythema: Present or absent. The percentage of patients in each category is reported.
Timepoint [17] 0 0
72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Secondary outcome [18] 0 0
Physician's Assessment of Range of Motion of the Most Affected Joint - The study physician assessed the range of motion of the most affected joint for range of motion on a 5-point Likert scale: Normal, mildly restricted, moderately restricted, severely restricted, immobilized. The percentage of patients in each category is reported.
Timepoint [18] 0 0
72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (24 weeks overall)
Secondary outcome [19] 0 0
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) - 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).
Timepoint [19] 0 0
7 days post dose (randomization), 24 weeks post-dose
Secondary outcome [20] 0 0
Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall) - 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.
Timepoint [20] 0 0
72 weeks overall
Secondary outcome [21] 0 0
Flare Rate Per Year - Flare rate was calculated as the number of new flares over the period of observation in years. Flare rate was calculated using only those new flares before switching to canakinumab.
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.
Timepoint [21] 0 0
72 weeks overall
Secondary outcome [22] 0 0
High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab - High sensitivity C-reactive protein (hsCRP) levels were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Timepoint [22] 0 0
24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)
Secondary outcome [23] 0 0
Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab - Serum Amyloid A Protein (SAA) levels were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Timepoint [23] 0 0
24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)
Secondary outcome [24] 0 0
Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab - The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's assessments (pain intensity [Visual Analog Scale and Likert scale] and patient's global assessment of response to treatment). The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Timepoint [24] 0 0
72 hours post-dose , 7 days post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)
Secondary outcome [25] 0 0
Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) - 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). The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Timepoint [25] 0 0
72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Secondary outcome [26] 0 0
Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab - Patients made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. Percentage of participants in each category for both core and extension periods were measured. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Timepoint [26] 0 0
72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Secondary outcome [27] 0 0
Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab - The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that "there is pain", patient states "there is pain and winces", and patient states "there is pain, winces, and withdraws" on palpation or passive movement of the affected study joint; The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Timepoint [27] 0 0
72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Secondary outcome [28] 0 0
Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab - The study physician assessed the most affected joint for: Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Timepoint [28] 0 0
72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Secondary outcome [29] 0 0
Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab - The study physician assessed the most affected joint for Erythema: Present or absent. The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Timepoint [29] 0 0
72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
Recruitment hospital [2] 0 0
Novartis Investigative Site - Fitzroy
Recruitment hospital [3] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [4] 0 0
Novartis Investigative Site - Daw Park SA
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
- Fitzroy
Recruitment postcode(s) [3] 0 0
- Heidelberg
Recruitment postcode(s) [4] 0 0
- Daw Park SA
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Gozee
Country [2] 0 0
Canada
State/province [2] 0 0
Newfoundland and Labrador
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Colombia
State/province [4] 0 0
Barranquilla
Country [5] 0 0
Colombia
State/province [5] 0 0
Bogota
Country [6] 0 0
Colombia
State/province [6] 0 0
Bucaramanga
Country [7] 0 0
Estonia
State/province [7] 0 0
Parnu
Country [8] 0 0
Estonia
State/province [8] 0 0
Tallinn
Country [9] 0 0
Estonia
State/province [9] 0 0
Tartu
Country [10] 0 0
Germany
State/province [10] 0 0
Bayreuth
Country [11] 0 0
Germany
State/province [11] 0 0
Berlin
Country [12] 0 0
Germany
State/province [12] 0 0
Leipzig
Country [13] 0 0
Germany
State/province [13] 0 0
Loehne
Country [14] 0 0
Germany
State/province [14] 0 0
Magdeburg
Country [15] 0 0
Germany
State/province [15] 0 0
Munich
Country [16] 0 0
Guatemala
State/province [16] 0 0
Guatemala City
Country [17] 0 0
Latvia
State/province [17] 0 0
Riga
Country [18] 0 0
Latvia
State/province [18] 0 0
Valmiera
Country [19] 0 0
Lithuania
State/province [19] 0 0
Kaunas
Country [20] 0 0
Lithuania
State/province [20] 0 0
Kedainiai
Country [21] 0 0
Lithuania
State/province [21] 0 0
Klaipeda
Country [22] 0 0
Lithuania
State/province [22] 0 0
Siauliai
Country [23] 0 0
Lithuania
State/province [23] 0 0
Vilnius
Country [24] 0 0
Mexico
State/province [24] 0 0
Culiacan
Country [25] 0 0
Mexico
State/province [25] 0 0
Guadalajara
Country [26] 0 0
Mexico
State/province [26] 0 0
Mexicali
Country [27] 0 0
Norway
State/province [27] 0 0
Oslo
Country [28] 0 0
Poland
State/province [28] 0 0
Katowice
Country [29] 0 0
Poland
State/province [29] 0 0
Kutno
Country [30] 0 0
Poland
State/province [30] 0 0
Lublin
Country [31] 0 0
Poland
State/province [31] 0 0
Wroclaw
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Moscow
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Yaroslavl
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Yekaterinburg
Country [35] 0 0
Singapore
State/province [35] 0 0
Singapore
Country [36] 0 0
Sweden
State/province [36] 0 0
Goeteborg
Country [37] 0 0
Sweden
State/province [37] 0 0
Stockholm
Country [38] 0 0
Switzerland
State/province [38] 0 0
Lausanne
Country [39] 0 0
Ukraine
State/province [39] 0 0
Donetsk
Country [40] 0 0
Ukraine
State/province [40] 0 0
Kyiv
Country [41] 0 0
Ukraine
State/province [41] 0 0
Lviv
Country [42] 0 0
Ukraine
State/province [42] 0 0
Zaporizhzhya

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01029652
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications