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)

Novartis

Status and phase: Completed; Phase 3

Conditions: Acute Gout

Treatments: Drug: Placebo to canakinumab; Drug: Placebo to triamcinolone acetonide; Drug: Canakinumab 150 mg; Drug: Triamcinolone acetonide 40 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01029652

CACZ885H2356E1 (Other Identifier)

2009-015018-23 (EudraCT Number)

CACZ885H2356

CACZ885H2356E2 (Other Identifier)

Details and patient eligibility

About

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.

Full description

Masking:

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

Enrollment: 230 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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230 participants in 2 patient groups

Canakinumab 150 mg

Experimental group

Description:

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

Treatment:

Drug: Canakinumab 150 mg

Drug: Placebo to triamcinolone acetonide

Triamcinolone acetonide 40 mg

Active Comparator group

Description:

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.

Treatment:

Drug: Triamcinolone acetonide 40 mg

Drug: Placebo to canakinumab