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 (β-RELIEVED)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

ClinicalTrials.gov Identifier:

NCT01029652

First received: December 9, 2009

Last updated: September 26, 2012

Last verified: September 2012

History of Changes

Results First Received: July 26, 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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Two patients randomized to canakinumab did not receive any study medication and were discontinued from the core study on the day of randomization, with the reason for discontinuation listed as Administrative Problems.

Reporting Groups

	Description
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 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. After completing the first extension study, patients were offered to enter the 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 the core study
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. No patient received triamcinolone acetonide in second extension Study .

Description

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 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.

After completing the first extension study, patients were offered to enter the 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 the core study

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. No patient received triamcinolone acetonide in second extension Study .

Participant Flow for 3 periods

Period 1: Core Study (0-12 Weeks)

	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
STARTED	115	115
Full Analysis Set (FAS), Safety Set	113	115
COMPLETED	109	105
NOT COMPLETED	6	10
Unsatisfactory therapeutic effect	0	4
Patient Withdrew Consent	1	3
Lost to Follow-up	3	1
Administrative problems	2	1
Death	0	1

Period 2: Extension Study 1 (12-24 Weeks)

	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
STARTED	90	85
COMPLETED	87	80
NOT COMPLETED	3	5
Unsatisfactory therapeutic effect	0	1
Lost to Follow-up	2	3
Protocol Deviation	1	0
Withdrawal by Subject	0	1

Period 3: Extension Study 2 (25-72 Weeks)

	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
STARTED	69	66
Re-treated With or Switch to Canakinumab	69 ^[1]	39 ^[2]
COMPLETED	68	63
NOT COMPLETED	1	3
Death	1	1
Unsatisfactory therapeutic effect	0	1
Withdrawal by Subject	0	1

[1]	Includes patients re-treated with canakinumab over 72 weeks study duration overall
[2]	Includes patients switched to canakinumab from Week 25 - Week 72

Baseline Characteristics

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Reporting Groups

	Description
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 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.
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.
Total	Total of all reporting groups

Baseline Measures

	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg	Total
Number of Participants [units: participants]	113	115	228
Age ^[1] [units: years] Mean ± Standard Deviation	54 ± 11.18	54.6 ± 10.71	54.3 ± 10.93
Age, Customized [units: participants]
< 65 years	92	92	184
≥ 65 - 74 years	16	21	37
≥ 75 years	5	2	7
Gender [units: participants]
Female	12	7	19
Male	101	108	209

[1]	Two patients randomized to canakinumab were not included in the data set (safety set) used to calculate demographic data as they did not receive any study medication and were discontinued from the study on the day of randomization.

Outcome Measures

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1. Primary:

Time to First New Flare [ Time Frame: 12 weeks ]

Show Outcome Measure 1

2. Primary:

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) ]

Show Outcome Measure 2

3. Primary:

Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) [ Time Frame: 24 weeks overall ]

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4. Primary:

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

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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 (0-100mm VAS) [ Time Frame: From baseline to 7 days post dose (randomization) ]

Show Outcome Measure 5

6. Secondary:

Time to Complete Resolution of Pain [ Time Frame: 7 days post-dose (randomization) ]

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7. Secondary:

Percentage of Participants With Complete Resolution of Pain [ Time Frame: 7 days post-dose (randomization) ]

Show Outcome Measure 7

8. Secondary:

Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks [ Time Frame: 12 weeks ]

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9. Secondary:

Mean Number of New Gout Flares Per Patient [ Time Frame: 12 weeks ]

Show Outcome Measure 9

10. Secondary:

SF36 Physical Function Score at Week 12 [ Time Frame: Week 12 ]

Show Outcome Measure 10

11. Secondary:

Time to First New Flare [ Time Frame: 24 weeks ]

Show Outcome Measure 11

12. Secondary:

Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study [ Time Frame: 24 weeks ]

Show Outcome Measure 12

13. Secondary:

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) ]

Show Outcome Measure 13

14. Secondary:

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) ]

Show Outcome Measure 14

15. Secondary:

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) ]

Show Outcome Measure 15

16. Secondary:

Amount of Rescue Medication Taken [ Time Frame: 7 days last post-baseline flare (during 24 weeks) ]

Show Outcome Measure 16

17. Secondary:

Percentage of Participants Who Took Rescue Medication [ Time Frame: during 12 weeks core, 24 weeks overall ]

Show Outcome Measure 17

18. Secondary:

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) ]

Show Outcome Measure 18

19. Secondary:

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) ]

Show Outcome Measure 19

20. Secondary:

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) ]

Show Outcome Measure 20

21. Secondary:

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) ]

Show Outcome Measure 21

22. Secondary:

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) ]

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23. Secondary:

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 ]

Show Outcome Measure 23

24. Secondary:

Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall) [ Time Frame: 72 weeks overall ]

Show Outcome Measure 24

25. Secondary:

Flare Rate Per Year [ Time Frame: 72 weeks overall ]

Show Outcome Measure 25

26. Secondary:

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) ]

Show Outcome Measure 26

27. Secondary:

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) ]

Show Outcome Measure 27

28. Secondary:

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) ]

Show Outcome Measure 28

29. Secondary:

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) ]

Show Outcome Measure 29

30. Secondary:

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) ]

Show Outcome Measure 30

31. Secondary:

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) ]

Show Outcome Measure 31

32. Secondary:

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) ]

Show Outcome Measure 32

33. Secondary:

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) ]

Show Outcome Measure 33

Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

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
Bioanalytical results: With analytical method used, anti-canakinumab antibodies were detected in 10 patients. However, no patients showed any unexpected PK/ PD profile nor had adverse events suggestive of immunogenicity.

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:	NCT01029652 History of Changes
Obsolete Identifiers:	NCT01071213, NCT01160016
Other Study ID Numbers:	CACZ885H2356, 2009-015018-23
Study First Received:	December 9, 2009
Results First Received:	July 26, 2011
Last Updated:	September 26, 2012
Health Authority:	United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Lithuania: State Medicine Control Agency - Ministry of Health Belgium: Federal Agency for Medicinal Products and Health Products Canada: Health Canada Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Estonia: The State Agency of Medicine Germany: Paul-Ehrlich-Institut Guatemala: Ministry of Public Health and Social Assistance Mexico: Ministry of Health Norway: Norwegian Medicines Agency Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Russia: Pharmacological Committee, Ministry of Health Singapore: Health Sciences Authority Sweden: Medical Products Agency Switzerland: Swissmedic Ukraine: Ministry of Health

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