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

NCT01029652 | Completed Phase 3 Results

• 4 other identifiers: CACZ885H23562009-015018-23CACZ885H2356E1CACZ885H2356E2
• Study Type: interventional
• Target: 230
• Locations: 17 countries
• Sites: 47

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.

Conditions

Acute Gout

Keywords

frequent flares; gout; anti-interleukin-1β monoclonal antibody

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  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)

  From baseline to 7 days post dose (randomization)

• Time to Complete Resolution of Pain

  7 days post-dose (randomization)

• Percentage of Participants With Complete Resolution of Pain

  7 days post-dose (randomization)

• Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks

  12 weeks

• Mean Number of New Gout Flares Per Patient

  12 weeks

Study Arms (2)

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

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.

Drug: Triamcinolone acetonide 40 mg; Drug: Placebo to canakinumab

Interventions

Canakinumab 150 mg DRUG

Canakinumab 150 mg was supplied in 6 mL glass vials each containing nominally 150 mg canakinumab (plus 20% overfill).

Canakinumab 150 mg

Triamcinolone acetonide 40 mg DRUG

Triamcinolone acetonide 40 mg was supplied as a suspension.

Triamcinolone acetonide 40 mg

Placebo to canakinumab DRUG

Placebo to canakinumab was supplied in 6 mL glass vials containing placebo powder as a lyophilized cake.

Triamcinolone acetonide 40 mg

Placebo to triamcinolone acetonide DRUG

Placebo triamcinolone acetonide was supplied as a lipid emulsion similar in appearance to triamcinolone acetonide.

Canakinumab 150 mg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• \- Continuation in this extension study was considered inappropriate by the treating physician.
• Extension Study 2:
• Continuation in this extension study was considered inappropriate by the treating physician

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (47)

Novartis Investigative Site

Darlinghurst, New South Wales, Australia

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Novartis Investigative Site

Fitzroy, Victoria, Australia

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Heidelberg, Victoria, Australia

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Daw Park SA, Australia

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Gozée, Belgium

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Mount Pearl, Newfoundland and Labrador, Canada

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St. John's, Newfoundland and Labrador, Canada

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Hamilton, Ontario, Canada

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Barranquilla, Colombia

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Bogotá, Colombia

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Bucaramanga, Colombia

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Pärnu, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Bayreuth, Germany

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Berlin, Germany

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Leipzig, Germany

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Löhne, Germany

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Magdeburg, Germany

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Munich, Germany

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Guatemala City, Guatemala

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Riga, Latvia

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Valmiera, Latvia

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Kaunas, Lithuania

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Kėdainiai, Lithuania

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Klaipėda, Lithuania

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Šiauliai, Lithuania

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Vilnius, Lithuania

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Culiacán, Mexico

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Guadalajara, Mexico

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Mexicali, Mexico

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Oslo, Norway

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Katowice, Poland

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Kutno, Poland

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Lublin, Poland

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Wroclaw, Poland

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Moscow, Russia

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Yaroslavl, Russia

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Yekaterinburg, Russia

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Singapore, Singapore

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Gothenburg, Sweden

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Stockholm, Sweden

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Lausanne, Switzerland

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Donetsk, Ukraine

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Novartis Investigative Site

Kyiv, Ukraine

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Novartis Investigative Site

Lviv, Ukraine

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Novartis Investigative Site

Zaporizhzhya, Ukraine

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Related Publications (1)

• 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.

  PMID: 24122883 DERIVED

MeSH Terms

Conditions

Gout

Interventions

canakinumab; Triamcinolone Acetonide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

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

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2009
• First Posted: December 10, 2009
• Study Start: December 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: January 30, 2014
• Results First Posted: November 18, 2011

Record last verified: 2012-09

Locations

LI (5); GU (1); PL (4); RU (3); SE (2); UA (4); BE (1); CO (3); DE (6); CH (1); SG (1); ES (3); CA (3); AU (4); ME (3); LA (2); NO (1)