Clinical trial NCT01029652: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Gout
Keywords: frequent flares
gout
anti-interleukin-1β monoclonal antibody
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-12-10
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the 12-week core study was to demonstrate that canakinumab given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares in patients with frequent flares of gout for whom non-steroidal anti-inflammatory drugs (NSAIDs) and/ or colchicine are contraindicated, not tolerated, or ineffective. The efficacy of canakinumab was compared to the corticosteroid triamcinolone acetonide.

The purpose of the first 12-week extension study was to collect additional safety, tolerability and efficacy data in patients who have completed the core study CACZ885H2356.

The purpose of the second 48 week open-label extension study was to collect additional long-term safety and tolerability data in patients who have completed the first extension study CACZ885H2356E1.

Detailed description: Masking:

Core: Double Blind (Subject, Investigator) Extension 1: Double Blind (Subject, Investigator) Extension 2: Open-label, terminated

Eligibility 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

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.

Primary outcomes:
measure: Time to First New Flare
timeFrame: 12 weeks
measure: Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS)
timeFrame: 72 hours post-dose (randomization)
measure: Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall)
timeFrame: 24 weeks overall
measure: Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall)
timeFrame: 72 weeks overall
Secondary outcomes:
measure: 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)
timeFrame: From baseline to 7 days post dose (randomization)
measure: Time to Complete Resolution of Pain
timeFrame: 7 days post-dose (randomization)
measure: Percentage of Participants With Complete Resolution of Pain
timeFrame: 7 days post-dose (randomization)
measure: Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks
timeFrame: 12 weeks
measure: Mean Number of New Gout Flares Per Patient
timeFrame: 12 weeks
measure: SF36 Physical Function Score at Week 12
timeFrame: Week 12
measure: Time to First New Flare
timeFrame: 24 weeks
measure: Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study
timeFrame: 24 weeks
measure: Time to First Intake of Rescue Medication After the Last Post Baseline Flare.
timeFrame: 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
measure: Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension
timeFrame: 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
measure: Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale)
timeFrame: Last post-baseline flare (during 24 weeks overall)
measure: Amount of Rescue Medication Taken
timeFrame: 7 days last post-baseline flare (during 24 weeks)
measure: Percentage of Participants Who Took Rescue Medication
timeFrame: during 12 weeks core, 24 weeks overall
measure: High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall
timeFrame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
measure: Physician's Global Assessment of Response to Treatment
timeFrame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
measure: Patient's Global Assessment of Response to Treatment
timeFrame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
measure: Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint
timeFrame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
measure: Physician's Assessment of Range of Motion of the Most Affected Joint
timeFrame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (24 weeks overall)
measure: Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale)
timeFrame: 7 days post dose (randomization), 24 weeks post-dose
measure: Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall)
timeFrame: 72 weeks overall
measure: Flare Rate Per Year
timeFrame: 72 weeks overall
measure: High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab
timeFrame: 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)
measure: Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab
timeFrame: 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)
measure: Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab
timeFrame: 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)
measure: Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale)
timeFrame: 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)
measure: Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab
timeFrame: 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)
measure: Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab
timeFrame: 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)
measure: Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab
timeFrame: 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)
measure: Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab
timeFrame: 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)
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Fitzroy
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Daw Park SA
country: Australia
facility: Novartis Investigative Site
city: Gozee
country: Belgium
facility: Novartis Investigative site
city: Mount Pearl
country: Canada
facility: Novartis Investigative Site
state: Newfoundland and Labrador
city: St-John's
country: Canada
facility: Novartis Investigative site
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Novartis Investigative site
state: Ontario
city: Barranquilla
country: Colombia
facility: Novartis Investigative site
city: Bogota
country: Colombia
facility: Novartis Investigative site
city: Bucaramanga
country: Colombia
facility: Novartis Investigative site
city: Parnu
country: Estonia
facility: Novartis Investigative site
city: Tallinn
country: Estonia
facility: Novartis Investigative site
city: Tartu
country: Estonia
facility: Novartis Investigative site
city: Bayreuth
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Loehne
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Munich
country: Germany
facility: Novartis Investigative site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Valmiera
country: Latvia
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
city: Kedainiai
country: Lithuania
facility: Novartis Investigative Site
city: Klaipeda
country: Lithuania
facility: Novartis Investigative site
city: Siauliai
country: Lithuania
facility: Novartis Investigative Site
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Culiacan
country: Mexico
facility: Novartis Investigative site
city: Guadalajara
country: Mexico
facility: Novartis Investigative site
city: Mexicali
country: Mexico
facility: Novartis Investigative site
city: Oslo
country: Norway
facility: Novartis Investigative site
city: Katowice
country: Poland
facility: Novartis Investigative site
city: Kutno
country: Poland
facility: Novartis Investigative site
city: Lublin
country: Poland
facility: Novartis Investigative site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative site
city: Yekaterinburg
country: Russian Federation
facility: Novartis Investigative site
city: Singapore
country: Singapore
facility: Novartis Investigative site
city: Goeteborg
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Donetsk
country: Ukraine
facility: Novartis Investigative Site
city: Kyiv
country: Ukraine
facility: Novartis Investigative Site
city: Lviv
country: Ukraine
facility: Novartis Investigative Site
city: Zaporizhzhya
country: Ukraine
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.