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 Colchicines Including a 12 Week Extension and a 1 Year Open-label Extension Study. (β-RELIEVED-II)

Novartis

Status and phase: Completed; Phase 3

Conditions: Acute Gout

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01080131

CACZ885H2357

2010-018913-32 (EudraCT Number)

CACZ885H2357E1 (Other Identifier)

Details and patient eligibility

About

The purpose of this 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 CACZ885H2357.

The purpose of the second one year open-label extension study was to confirm the long-term safety and tolerability of canakinumab in patients who had completed the first extension study.

Enrollment: 226 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, or intolerance, or lack of efficacy for non-steroidal anti-inflammatory drugs (NSAID) 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 Criteria:

• Completion of the first extension study CACZ885H2357E1. A patient was defined as completing the first extension study if they completed the study up to and including Visit 10).

Exclusion Criteria:

-Continuation in this second 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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226 participants in 2 patient groups

Canakinumab 150 mg

Experimental group

Description:

Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants 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. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year, for a total duration of 18 months.

Treatment:

Drug: Canakinumab 150 mg

Drug: Placebo to triamcinolone acetonide

Triamcinolone acetonide 40 mg

Active Comparator group

Description:

Participants received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Participants 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. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year. Triamcinolone acetonide was not to be administered in the second extension study.

Treatment:

Drug: Placebo to canakinumab

Drug: Triamcinolone acetonide 40 mg