Efficacy and Safety of a Single Dose of Canakinumab (ACZ885) in Hospitalized Patients With Acute Gout

A Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group Study of a Single Dose of ACZ885 in Hospitalized Patients With Acute Gout

This is an exploratory proof-of-concept study to evaluate the safety and efficacy of canakinumab (ACZ885) for inflammation and pain associated with acute gouty arthritis.

Study Overview

• Status: Completed
• Conditions: Arthritis, Gouty
• Intervention / Treatment: Biological: canakinumab; Other: placebo matching dexamethasone; Drug: dexamethasone; Other: placebo matching canakinumab

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Lausanne, Switzerland
    • Novartis Investigator Site
• United Kingdom
  • Glasgow, United Kingdom
    • Novartis Investigator Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Novartis Investigator Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• score over 50 on the 0-100 VAS pain scale
• acute, confirmed gout flare for no longer than 3 days

Exclusion Criteria:

• Treatment with biological anti-tumor necrosis factor (anti-TNF) within the past 3 months
• Anti-inflammatory medication for the treatment of acute gout within the previous 24 hours
• Pregnant or breastfeeding women
• Major surgery with high infection risk
• History of severe allergy to food or drugs
• History or risk of tuberculosis
• Active infection

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canakinumab; Canakinumab 10 mg/kg intravenous infusion and placebo matching dexamethasone intravenous infusion on Day 1.	Biological: canakinumab; 10 mg/kg intravenous infusion 250 mL over 2 hours.; Other Names: ACZ885; Ilaris®; Other: placebo matching dexamethasone; Placebo intravenous infusion.
Active Comparator: Dexamethasone; Dexamethasone 12 mg intravenous infusion and placebo matching canakinumab on Day 1.	Drug: dexamethasone; 12 mg intravenous infusion 50 mL over 30 minutes.; Other: placebo matching canakinumab; 5% glucose in water intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Improvement in Gout at 72 Hours Post-dose Using a Likert Scale	72 hours following treatment, patients were asked the question: "How would you rate the improvement in your gout since receiving the study medication?" Patients rated their improvement on the Likert 5-point scale: 1=Excellent, 2=Good, 3=Acceptable,4=Slight and 5=Poor. Improvement was assessed by determining patients who scored a "good" or "excellent" response.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority of a Single Dose of Canakinumab Compared to Dexamethasone During Treatment Period		72 hours
Time to Recurrence of the Symptoms of Acute Gout (if Applicable) During Treatment Period	Time to recurrence is defined as from the point of improvement (good to excellent on Likert scale) to recurrence.	4 months
Time to Walk Independently (if Applicable) During Treatment Period		4 months
Number of Participants With Discontinuation of Treatment Due to Adverse Events, Deaths or Serious Adverse Events During the Study	Additional safety information can be found in the Adverse Event section.	4 months
Change in C-reactive Protein (CRP) From Baseline at Month 4	Blood was collected at Baseline and Month 4 for CRP to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement.	Baseline, Month 4
Change in Serum Amyloid A Protein (SAA) From Baseline at Month 4	Blood was collected at Baseline and Month 4 for SAA to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement.	Baseline, Month 4
ACZ885 (Canakinumab) Pharmacokinetics (PK) Serum Concentration During the Treatment Period	Blood was collected for ACZ885 (canakinumab) levels at baseline and Days 0.25, 1, 3, 6, 20, 34, 55 and 119. Serum was analyzed by means of a competitive Enzyme linked immunosorbant assay (ELISA).	Baseline, Days 0.25, 1, 3, 6, 20, 34, 55 and 119
Change From Baseline in Pain Using a Visual Analog Scale at Month 4	Patients rated their pain on a 100 millimeter (mm) visual analog scale, ranging from no pain (0) to unbearable pain (100). A negative change from baseline indicates improvement.	Baseline, Month 4
Number of Patients Who Took Rescue Medication	Patients who did not improve by 72 hours post-dose (i.e. patients who show a pain Visual Analog (VAS) decrease of less than 50 % from baseline (Day 1, pre-dose) would have been treated with rescue medication of methylprednisolone 80 mg intravenous or intramuscular once at the discretion of the clinical investigator.	4 months

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: April 18, 2008
• First Submitted That Met QC Criteria: April 21, 2008
• First Posted (Estimate): April 22, 2008

Study Record Updates

• Last Update Posted (Estimate): January 7, 2013
• Last Update Submitted That Met QC Criteria: December 4, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Pain; ACZ885; Arthritis Gouty; IL1B protein
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Arthritis; Arthritis, Gouty; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Antibodies, Monoclonal
• Other Study ID Numbers: CACZ885A2212