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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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)
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)
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)
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)
Timepoint [1] 0 0
From baseline to 7 days post dose (randomization)
Secondary outcome [2] 0 0
Time to Complete Resolution of Pain
Timepoint [2] 0 0
7 days post-dose (randomization)
Secondary outcome [3] 0 0
Percentage of Participants With Complete Resolution of Pain
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
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Mean Number of New Gout Flares Per Patient
Timepoint [5] 0 0
12 weeks
Secondary outcome [6] 0 0
SF36 Physical Function Score at Week 12
Timepoint [6] 0 0
Week 12
Secondary outcome [7] 0 0
Time to First New Flare
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
Timepoint [8] 0 0
24 weeks
Secondary outcome [9] 0 0
Time to First Intake of Rescue Medication After the Last Post Baseline Flare.
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
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)
Timepoint [11] 0 0
Last post-baseline flare (during 24 weeks overall)
Secondary outcome [12] 0 0
Amount of Rescue Medication Taken
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
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
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
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
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
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
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)
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)
Timepoint [20] 0 0
72 weeks overall
Secondary outcome [21] 0 0
Flare Rate Per Year
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
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
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
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)
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
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
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
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
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
Sex
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.