Acute GoutPhase 3β-RELIEVEDNCT01029652
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
A Phase 3 study testing Canakinumab 150 mg and Triamcinolone acetonide 40 mg in people with Acute Gout, run by Novartis Pharmaceuticals at 47 sites in 17 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Gout
- What is being tested?
- Canakinumab 150 mg and Triamcinolone acetonide 40 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 230 participants
- Where
- 47 sitesin 17 countries
- Study dates
- Dec 2009to Oct 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 15Show fewer
- 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.
- 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).
- -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.
Trial locations and contacts
47 sites in 17 countries.
47 sites in 17 countries
Germany6 sites
Novartis Investigative Site
Bayreuth
Novartis Investigative Site
Berlin
Novartis Investigative Site
Leipzig
Novartis Investigative Site
Löhne
Novartis Investigative Site
Magdeburg
Novartis Investigative site
Munich
Lithuania5 sites
Novartis Investigative Site
Kaunas
Novartis Investigative Site
Kėdainiai
Novartis Investigative site
Klaipėda
Novartis Investigative Site
Šiauliai
Novartis Investigative Site
Vilnius
Australia4 sites
Novartis Investigative Site
Darlinghurst, New South Wales
Novartis Investigative Site
Daw Park SA
Novartis Investigative Site
Fitzroy, Victoria
Novartis Investigative Site
Heidelberg, Victoria
Poland4 sites
Novartis Investigative site
Katowice
Novartis Investigative site
Kutno
Novartis Investigative site
Lublin
Novartis Investigative Site
Wroclaw
Ukraine4 sites
Novartis Investigative Site
Donetsk
Novartis Investigative Site
Kyiv
Novartis Investigative Site
Lviv
Novartis Investigative Site
Zaporizhzhya
Canada3 sites
Novartis Investigative site
Hamilton, Ontario
Novartis Investigative Site
Mount Pearl, Newfoundland and Labrador
Novartis Investigative site
St. John's, Newfoundland and Labrador
Colombia3 sites
Novartis Investigative site
Barranquilla
Novartis Investigative site
Bogotá
Novartis Investigative site
Bucaramanga
Estonia3 sites
Novartis Investigative site
Pärnu
Novartis Investigative site
Tallinn
Novartis Investigative site
Tartu
Mexico3 sites
Novartis Investigative site
Culiacán
Novartis Investigative site
Guadalajara
Novartis Investigative site
Mexicali
Russia3 sites
Novartis Investigative site
Moscow
Novartis Investigative site
Yaroslavl
Novartis Investigative site
Yekaterinburg
Latvia2 sites
Novartis Investigative Site
Riga
Novartis Investigative Site
Valmiera
Sweden2 sites
Novartis Investigative Site
Gothenburg
Novartis Investigative site
Stockholm
About this study
Official 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
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.
Read the detailed description
Masking:
Core: Double Blind (Subject, Investigator) Extension 1: Double Blind (Subject, Investigator) Extension 2: Open-label, terminated
- Conditions
- Acute Gout
- Being tested
- Canakinumab 150 mg, Triamcinolone acetonide 40 mg, Placebo to canakinumab, Placebo to triamcinolone acetonide
- Keywords
- frequent flares, gout, anti-interleukin-1β monoclonal antibody
- Medical subject headings
- Gout
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Canakinumab 150 mgDrug
Canakinumab 150 mg was supplied in 6 mL glass vials each containing nominally 150 mg canakinumab (plus 20% overfill).
Triamcinolone acetonide 40 mgDrug
Triamcinolone acetonide 40 mg was supplied as a suspension.
Placebo to canakinumabDrug
Placebo to canakinumab was supplied in 6 mL glass vials containing placebo powder as a lyophilized cake.
Placebo to triamcinolone acetonideDrug
Placebo triamcinolone acetonide was supplied as a lipid emulsion similar in appearance to triamcinolone acetonide.
| Study group | Role | What they receive |
|---|---|---|
| Canakinumab 150 mg | Experimental | 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 Receives: Drug: Canakinumab 150 mg; Drug: Placebo to triamcinolone acetonide |
| Triamcinolone acetonide 40 mg | Active comparator | 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. Receives: Drug: Triamcinolone acetonide 40 mg; Drug: Placebo to canakinumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
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.
Measured: 72 hours post-dose (randomization)
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.
Measured: 24 weeks overall
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.
Measured: 72 weeks overall
Secondary outcomes (29)
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.
Measured: From baseline to 7 days post dose (randomization)
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.
Measured: 7 days post-dose (randomization)
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.
Measured: 7 days post-dose (randomization)
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.
Measured: 12 weeks
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.
Measured: 12 weeks
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.
Measured: Week 12
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.
Measured: 24 weeks
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.
Measured: 24 weeks
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.
Measured: 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
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.
Measured: 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
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).
Measured: Last post-baseline flare (during 24 weeks overall)
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.
Measured: 7 days last post-baseline flare (during 24 weeks)
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.
Measured: during 12 weeks core, 24 weeks overall
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.
Measured: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
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).
Measured: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
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.
Measured: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
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.
Measured: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
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.
Measured: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (24 weeks overall)
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).
Measured: 7 days post dose (randomization), 24 weeks post-dose
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.
Measured: 72 weeks overall
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.
Measured: 72 weeks overall
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute GoutStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01029652
- Sponsor's protocol ID
- CACZ885H2356
- Other IDs
- 2009-015018-23, CACZ885H2356E1, CACZ885H2356E2, 2009
- Acronym
- β-RELIEVED
- Status last verified
- Sep 2012
- First submitted
- 9 Dec 2009
- Last updated
- 30 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 24122883
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01029652
- Acronym / sponsor ID
- β-RELIEVED / CACZ885H2356
- Conditions
- Acute Gout
- Keywords
- frequent flares, gout, anti-interleukin-1β monoclonal antibody
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 10 Dec 2009 (estimated)
- Results
- Posted 18 Nov 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Canakinumab 150 mg | Experimental | Drug: Canakinumab 150 mg, Drug: Placebo to triamcinolone acetonidePatients 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 |
| Triamcinolone acetonide 40 mg | Active comparator | Drug: Triamcinolone acetonide 40 mg, Drug: Placebo to canakinumabPatients 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Canakinumab 150 mgCanakinumab 150 mg was supplied in 6 mL glass vials each containing nominally 150 mg canakinumab (plus 20% overfill). | Drug | Canakinumab 150 mg |
| Triamcinolone acetonide 40 mgTriamcinolone acetonide 40 mg was supplied as a suspension. | Drug | Triamcinolone acetonide 40 mg |
| Placebo to canakinumabPlacebo to canakinumab was supplied in 6 mL glass vials containing placebo powder as a lyophilized cake. | Drug | Triamcinolone acetonide 40 mg |
| Placebo to triamcinolone acetonidePlacebo triamcinolone acetonide was supplied as a lipid emulsion similar in appearance to triamcinolone acetonide. | Drug | Canakinumab 150 mg |
Primary outcome
Time to First New Flare
Time frame: 12 weeks
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.
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)
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.
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall)
Time frame: 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.
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall)
Time frame: 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.
29 secondary outcomes
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)
Time to Complete Resolution of Pain
Time frame: 7 days post-dose (randomization)
Percentage of Participants With Complete Resolution of Pain
Time frame: 7 days post-dose (randomization)
Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks
Time frame: 12 weeks
Mean Number of New Gout Flares Per Patient
Time frame: 12 weeks
SF36 Physical Function Score at Week 12
Time frame: Week 12
Time to First New Flare
Time frame: 24 weeks
Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study
Time frame: 24 weeks
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)
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)
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)
Amount of Rescue Medication Taken
Time frame: 7 days last post-baseline flare (during 24 weeks)
Percentage of Participants Who Took Rescue Medication
Time frame: during 12 weeks core, 24 weeks overall
High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Physician's Global Assessment of Response to Treatment
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Patient's Global Assessment of Response to Treatment
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Physician's Assessment of Range of Motion of the Most Affected Joint
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (24 weeks overall)
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale)
Time frame: 7 days post dose (randomization), 24 weeks post-dose
Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall)
Time frame: 72 weeks overall
Flare Rate Per Year
Time frame: 72 weeks overall
High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab
Time frame: 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)
Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab
Time frame: 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)
Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab
Time frame: 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)
Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale)
Time frame: 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)
Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab
Time frame: 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)
Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab
Time frame: 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)
Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab
Time frame: 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)
Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24122883Chakraborty 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
47 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Canakinumab 150 mg and Triamcinolone acetonide 40 mg in people with Acute Gout, run by Novartis Pharmaceuticals at 47 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in Germany, Lithuania, Australia, Poland, Ukraine and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to First New Flare (time frame: 12 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01029652, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2014.