Canakinumab in the Treatment of Acute Gout Flares and Prevention of New Flares in Patients Unable to Use Non-steroidal Anti-inflammatory Drugs (NSAIDs) and/or Colchicines Including a 12 Week Extension and a 1 Year Open-label Extension Study. (β-RELIEVED-II)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01080131
First received: March 2, 2010
Last updated: December 24, 2013
Last verified: April 2013
Results First Received: August 30, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Acute Gout
Interventions: Drug: Canakinumab 150 mg
Drug: Triamcinolone acetonide 40 mg
Drug: Placebo to canakinumab
Drug: Placebo to triamcinolone acetonide

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Canakinumab 150 mg

Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. In the first extension study participants completing the 12 week core study could continue to be treated on demand with the same treatment for another 12 weeks for any new gout flare.

In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc for any new flare for an additional year, for a total duration of 18 months.

Triamcinolone Acetonide 40 mg

Participants received 1 intramuscular injection of triamcinolone acetonide 40 mg and 1 sc injection of placebo to canakinumab on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose.

In the first extension study participants completing the 12 week core study could continue to be treated on demand with the same treatment for another 12 weeks for any new gout flare.

In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc for any new flare for an additional year. Triamcinolone acetonide was not to be administered in the second extension study.


Participant Flow for 3 periods

Period 1:   Core Study (0- 12 Weeks)
    Canakinumab 150 mg     Triamcinolone Acetonide 40 mg  
STARTED     112     114  
COMPLETED     99     103  
NOT COMPLETED     13     11  
Abnormal laboratory value(s)                 1                 1  
Patient withdrew consent                 6                 4  
Lost to Follow-up                 5                 3  
Administrative problems                 0                 1  
Death                 1                 0  
Protocol deviation                 0                 2  

Period 2:   Extension Study 1 (12 -24 Weeks)
    Canakinumab 150 mg     Triamcinolone Acetonide 40 mg  
STARTED     84     76  
COMPLETED     78     72  
NOT COMPLETED     6     4  
Adverse Event                 1                 0  
Unsatisfactory Therapeutic Effect                 0                 1  
Withdrawal by Subject                 4                 3  
Lost to Follow-up                 1                 0  

Period 3:   Extension Study 2 (25-72 Weeks)
    Canakinumab 150 mg     Triamcinolone Acetonide 40 mg  
STARTED     72     65  
Re-treated With or Switch to Canakinumab     62 [1]   41 [2]
COMPLETED     64     54  
NOT COMPLETED     8     11  
Adverse Event                 1                 2  
Withdrawal by Subject                 3                 4  
Lost to Follow-up                 4                 5  
[1] Includes patients re-treated with canakinumab at any time during the 72 weeks
[2] Includes patients switched to canakinumab from Week 25 - Week 72



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Canakinumab 150 mg

Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. In the first extension study participants completing the 12 week core study could continue to be treated on demand with the same treatment for another 12 weeks for any new gout flare.

In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc for any new flare for an additional year, for a total duration of 18 months.

Triamcinolone Acetonide 40 mg

Participants received 1 intramuscular injection of triamcinolone acetonide 40 mg and 1 sc injection of placebo to canakinumab on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose.

In the first extension study participants completing the 12 week core study could continue to be treated on demand with the same treatment for another 12 weeks for any new gout flare.

In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc for any new flare for an additional year. Triamcinolone acetonide was not to be administered in the second extension study.

Total Total of all reporting groups

Baseline Measures
    Canakinumab 150 mg     Triamcinolone Acetonide 40 mg     Total  
Number of Participants  
[units: participants]
  112     114     226  
Age  
[units: years]
Mean ± Standard Deviation
  50.6  ± 12.10     52.6  ± 12.28     51.6  ± 12.21  
Gender  
[units: participants]
     
Female     12     9     21  
Male     100     105     205  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to First New Flare: Survival Analysis During the 12 Weeks of Study   [ Time Frame: Baseline to 12 weeks ]

2.  Primary:   Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose   [ Time Frame: 72 hours post-dose (randomization) ]

3.  Primary:   Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks   [ Time Frame: During 24 weeks overall ]

4.  Primary:   Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall)   [ Time Frame: 72 weeks ]

5.  Secondary:   Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS)   [ Time Frame: Baseline to 7 days post-dose (randomization) ]

6.  Secondary:   Time to Complete Resolution of Pain; Survival Analysis   [ Time Frame: Baseline to 7 days post-dose (randomization) ]

7.  Secondary:   SF 36 Physical Function Score at Week 12   [ Time Frame: Week 12 ]

8.  Secondary:   Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study   [ Time Frame: Baseline to Week 12 ]

9.  Secondary:   Pharmacokinetic Concentrations   [ Time Frame: 12 weeks post-dose ]

10.  Secondary:   Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS)   [ Time Frame: 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose (randomization) ]

11.  Secondary:   Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS)   [ Time Frame: 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose for last post-baseline flare that occurred up until the end of the first extension study (24 weeks). ]

12.  Secondary:   Time to the First New Gout Flare During 24 Weeks   [ Time Frame: From randomization to the end of the first extension period (24 weeks). ]

13.  Secondary:   Mean Number of New Gout Flares Per Patient During 24 Weeks   [ Time Frame: 24 weeks ]

14.  Secondary:   Time to First Intake of Rescue Medication   [ Time Frame: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). ]

15.  Secondary:   Percentage of Participants Who Took Rescue Medication   [ Time Frame: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). ]

16.  Secondary:   Amount of Rescue Medication Taken   [ Time Frame: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). ]

17.  Secondary:   Physician’s Global Assessment of Response to Treatment   [ Time Frame: 72 hours post-dose and 24-weeks post-dose. ]

18.  Secondary:   Patient’s Global Assessment of Response to Treatment   [ Time Frame: 72 hours post-dose and 24 weeks post-dose ]

19.  Secondary:   Physician’s Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint   [ Time Frame: 72 hours post-dose and 24 weeks post-dose ]

20.  Secondary:   Physician’s Assessment of Range of Motion of the Most Affected Joint   [ Time Frame: 72 hours post-dose and 24 weeks post-dose ]

21.  Secondary:   High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels   [ Time Frame: 72 hours after the first dose for the baseline flare and 72 hours post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). ]

22.  Secondary:   Patient's Assessment of Gout Pain Intensity in the Most Affected Joint   [ Time Frame: 72 hours post-dose and 24 weeks post-dose ]

23.  Secondary:   Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme   [ Time Frame: From the onset of a new flare until re-dosing. First post-baseline new flare during 12 week core study and the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). ]

24.  Secondary:   Time to First New Flare: Survival Analysis by Treatment Over 72 Weeks   [ Time Frame: From randomization to the end of the second extension period (72 weeks). ]

25.  Secondary:   Flare Rate Per Year   [ Time Frame: From randomization to the end of the second extension period (72 weeks). ]

26.  Secondary:   Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab   [ Time Frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. ]

27.  Secondary:   Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab   [ Time Frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. ]

28.  Secondary:   Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab   [ Time Frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. ]

29.  Secondary:   Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab   [ Time Frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. ]

30.  Secondary:   Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab   [ Time Frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. ]

31.  Secondary:   Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab   [ Time Frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. ]

32.  Secondary:   High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab   [ Time Frame: 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. ]

33.  Secondary:   Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab   [ Time Frame: 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862 778-8300


No publications provided


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01080131     History of Changes
Obsolete Identifiers: NCT01137344, NCT01194921
Other Study ID Numbers: CACZ885H2357, 2010-018913-32, CACZ885H2357E1
Study First Received: March 2, 2010
Results First Received: August 30, 2011
Last Updated: December 24, 2013
Health Authority: Canada: Health Canada
Netherlands: Dutch Health Care Inspectorate
Russia: Pharmacological Committee, Ministry of Health
United States: Food and Drug Administration
Taiwan: Taiwan Food and Drug Administration