Targeted Dose Finding of Canakinumab (ACZ885) for Management of Acute Flare in Refractory or Contraindicated Gout Patients - Full Text View

Purpose

This 8-week study is designed to determine the target dose of canakinumab (ACZ885) for the management of acute flare in gout patients who are contraindicated to Non-Steroidal anti-inflammatory drugs and/or colchicine. The efficacy of ACZ885 will be compared to the corticosteroid triamcinolone acetonide.

Condition	Intervention	Phase
Acute Gout	Drug: Canakinumab Drug: Triamcinolone acetonide	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	An Adaptive Dose-ranging, Multi-center, Single-blind, Double-dummy, Active-controlled Trial to Determine the Target Dose of Canakinumab (ACZ885) in the Treatment of Acute Flares in Gout Patients Who Are Refractory or Contraindicated to NSAIDs and/or Colchicine

Resource links provided by NLM:

MedlinePlus related topics: Gout

Drug Information available for: Colchicine Triamcinolone diacetate Triamcinolone acetonide Triamcinolone Triamcinolone hexacetonide Sodium chloride Chlorine Canakinumab

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) [ Time Frame: at 24,48 and 72 hours post-baseline ] [ Designated as safety issue: No ]
Mean target dose at 24, 48 and 72 hours. Four models: Emax, Logistic, Linear in log-dose, Linear were selected to describe the potential dose-response curve and hence estimate the target dose of canakinumab using baseline Visual Analog Scale (VAS) and Body Mass Index (BMI) as covariates. Target dose was defined as the dose for which the efficacy is equivalent to the efficacy of triamcinolone acetonide 40 mg and was identified by assessing the dose response relationship with regards to the pain intensity in the target joint measured on a 0- 100 mm VAS (0= no pain and 100= unbearable pain).

Secondary Outcome Measures:

The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide [ Time Frame: Baseline,at 72 hrs post-dose and 7 days post-dose ] [ Designated as safety issue: No ]
The change in pain intensity from baseline to 72 hours and 7 days post dose as measured on a 0-100 mm Visual Analog Scale(VAS): 0= no pain and 100= severe pain. Analysis of Covariance (ANCOVA) with treatment group, VAS at baseline and Body mass Index (BMI) at baseline as covariates. Change from baseline = (post-baseline measurement - baseline).
Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment [ Time Frame: at 72 hours post-baseline ] [ Designated as safety issue: No ]
Participants scored their global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Slight and Poor.
The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint [ Time Frame: Baseline, within 7 days after randomization ] [ Designated as safety issue: No ]
The median time in days to at least 50% reduction in Pain intensity from baseline as measured by Visual Analog Scale (VAS) for each treatment group. Participants scored their pain intensity in the target joint on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100).
High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group [ Time Frame: at 72 hours and 7 days, 4 and 8 weeks post-dose ] [ Designated as safety issue: No ]
High sensitivity C-reactive protein (hsCRP) was determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.

ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates.
Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group [ Time Frame: at 72 hours and 7 days, 4 and 8 weeks post-dose ] [ Designated as safety issue: No ]
Serum amyloid A (SAA) were determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.

ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates.
Amount of Rescue Medication Taken for Each Treatment Group [ Time Frame: 7 days after study drug administration ] [ Designated as safety issue: No ]
Participants who had difficulty in tolerating their pain after the 6-hour post-dose pain assessments and during the first 7 study days were allowed to take a maximum of 30 mg prednisolone (or equivalent dose of prednisone [30 mg]) orally once a day for a maximum of 5 days. In addition, participants could use 500 mg acetaminophen (paracetamol) and/or 30 mg codeine as needed during the first 7 study days. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/dose or 180 mg/day of codeine was allowed during the first 7 days of the study.

Enrollment:	200
Study Start Date:	November 2008
Study Completion Date:	August 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Canakinumab 10 mg Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.
Experimental: Canakinumab 25 mg Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1.
Experimental: Canakinumab 50 mg Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1.
Experimental: Canakinumab 90 mg Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1.
Experimental: Canakinumab 150 mg Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1.
Active Comparator: Triamcinolone acetonide 40 mg Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once and placebo matching canakinumab s.c. once, on Day 1.	Drug: Triamcinolone acetonide Randomized patients received triamcinolone acetonide 40 mg i.m. once and placebo matching canakinumab s.c. once, on Day 1.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

History of at least 1 gout flare prior to the Screening Visit
Meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout.
Presence of acute gout flare for no longer than 5 days.
Baseline pain intensity > or = to 50 mm on the 0-100 mm VAS.
Contraindicated for, intolerant or unresponsive to NSAIDs, colchicine or both.

Exclusion Criteria:

Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis.
Presence of severe renal function impairment
Contraindication to intramuscular injection
Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment
Evidence of active pulmonary disease
Live vaccinations within 3 months prior to the start of the study
Use of forbidden therapy

Other protocol-defined inclusion/exclusion criteria applied

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00798369

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Sponsors and Collaborators

Novartis

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schlesinger N, De Meulemeester M, Pikhlak A, Yücel AE, Richard D, Murphy V, Arulmani U, Sallstig P, So A. Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study. Arthritis Res Ther. 2011 Mar 25;13(2):R53.

So A, De Meulemeester M, Pikhlak A, Yücel AE, Richard D, Murphy V, Arulmani U, Sallstig P, Schlesinger N. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. Arthritis Rheum. 2010 Oct;62(10):3064-76.

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00798369 History of Changes
Other Study ID Numbers:	CACZ885H2255, EudraCT 2008-004666-61
Study First Received:	November 25, 2008
Results First Received:	January 20, 2011
Last Updated:	April 9, 2012
Health Authority:	Argentina: Ministry of Health Belgium: Federal Agency for Medicinal Products and Health Products Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Russia: Pharmacological Committee, Ministry of Health Switzerland: Federal Office of Public Health Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

Keywords provided by Novartis:

Acute flares
Gout
Anti-interleukin-1β monoclonal antibody
Colchicine
Triamcinolone acetonide

Additional relevant MeSH terms:

Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Colchicine
Triamcinolone hexacetonide
Triamcinolone
Triamcinolone Acetonide
Antibodies, Monoclonal
Triamcinolone diacetate

Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Immunosuppressive Agents

ClinicalTrials.gov processed this record on May 16, 2013