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

NCT ID: NCT01029652

Last Updated: 2014-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2010-10-31

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

Conditions

Acute Gout

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Canakinumab 150 mg

Intervention Type: DRUG

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

Placebo to triamcinolone acetonide

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Triamcinolone acetonide 40 mg

Intervention Type: DRUG

Triamcinolone acetonide 40 mg was supplied as a suspension.

Placebo to canakinumab

Intervention Type: DRUG

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

Interventions

Canakinumab 150 mg

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

Intervention Type: DRUG

Triamcinolone acetonide 40 mg

Triamcinolone acetonide 40 mg was supplied as a suspension.

Intervention Type: DRUG

Placebo to canakinumab

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

Intervention Type: DRUG

Placebo to triamcinolone acetonide

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Darlinghurst, New South Wales, Australia

Novartis Investigative Site

Fitzroy, Victoria, Australia

Novartis Investigative Site

Heidelberg, Victoria, Australia

Novartis Investigative Site

Daw Park SA, , Australia

Novartis Investigative site

Gozée, , Belgium

Novartis Investigative Site

Mount Pearl, Newfoundland and Labrador, Canada

Novartis Investigative site

St. John's, Newfoundland and Labrador, Canada

Novartis Investigative site

Hamilton, Ontario, Canada

Novartis Investigative site

Barranquilla, , Colombia

Novartis Investigative site

Bogotá, , Colombia

Novartis Investigative site

Bucaramanga, , Colombia

Novartis Investigative site

Pärnu, , Estonia

Novartis Investigative site

Tallinn, , Estonia

Novartis Investigative site

Tartu, , Estonia

Novartis Investigative Site

Bayreuth, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Löhne, , Germany

Novartis Investigative Site

Magdeburg, , Germany

Novartis Investigative site

Munich, , Germany

Novartis Investigative Site

Guatemala City, , Guatemala

Novartis Investigative Site

Riga, , Latvia

Novartis Investigative Site

Valmiera, , Latvia

Novartis Investigative Site

Kaunas, , Lithuania

Novartis Investigative Site

Kėdainiai, , Lithuania

Novartis Investigative site

Klaipėda, , Lithuania

Novartis Investigative Site

Šiauliai, , Lithuania

Novartis Investigative Site

Vilnius, , Lithuania

Novartis Investigative site

Culiacán, , Mexico

Novartis Investigative site

Guadalajara, , Mexico

Novartis Investigative site

Mexicali, , Mexico

Novartis Investigative site

Oslo, , Norway

Novartis Investigative site

Katowice, , Poland

Novartis Investigative site

Kutno, , Poland

Novartis Investigative site

Lublin, , Poland

Novartis Investigative Site

Wroclaw, , Poland

Novartis Investigative site

Moscow, , Russia

Novartis Investigative site

Yaroslavl, , Russia

Novartis Investigative site

Yekaterinburg, , Russia

Novartis Investigative site

Singapore, , Singapore

Novartis Investigative Site

Gothenburg, , Sweden

Novartis Investigative site

Stockholm, , Sweden

Novartis Investigative Site

Lausanne, , Switzerland

Novartis Investigative Site

Donetsk, , Ukraine

Novartis Investigative Site

Kyiv, , Ukraine

Novartis Investigative Site

Lviv, , Ukraine

Novartis Investigative Site

Zaporizhzhya, , Ukraine

Countries

Australia; Belgium; Canada; Colombia; Estonia; Germany; Guatemala; Latvia; Lithuania; Mexico; Norway; Poland; Russia; Singapore; Sweden; Switzerland; Ukraine

References

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.

Reference Type: DERIVED

PMID: 24122883 (View on PubMed)

Other Identifiers

2009-015018-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CACZ885H2356E1

Identifier Type: OTHER

Identifier Source: secondary_id

CACZ885H2356E2

Identifier Type: OTHER

Identifier Source: secondary_id

CACZ885H2356

Identifier Type: -

Identifier Source: org_study_id

NCT01071213

Identifier Type: -

Identifier Source: nct_alias

NCT01160016

Identifier Type: -

Identifier Source: nct_alias