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

NCT00798369 | Completed Phase 2 Results

• 2 other identifiers: CACZ885H2255EudraCT 2008-004666-61
• Study Type: interventional
• Target: 200
• Locations: 11 countries
• Sites: 75

Brief Summary

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.

Conditions

Acute Gout

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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)

  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).

  at 24,48 and 72 hours post-baseline

Secondary Outcomes (6)

• The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide

  Baseline,at 72 hrs post-dose and 7 days post-dose

• Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment

  at 72 hours post-baseline

• The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint

  Baseline, within 7 days after randomization

• High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group

  at 72 hours and 7 days, 4 and 8 weeks post-dose

• Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group

  at 72 hours and 7 days, 4 and 8 weeks post-dose

Study Arms (6)

Canakinumab 10 mg

EXPERIMENTAL

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

Canakinumab 25 mg

EXPERIMENTAL

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

Canakinumab 50 mg

EXPERIMENTAL

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

Canakinumab 90 mg

EXPERIMENTAL

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

Canakinumab 150 mg

EXPERIMENTAL

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

Triamcinolone acetonide 40 mg

ACTIVE COMPARATOR

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

Interventions

Canakinumab DRUG

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.

Canakinumab 10 mg

Triamcinolone acetonide DRUG

Randomized patients received triamcinolone acetonide 40 mg i.m. once and placebo matching canakinumab s.c. once, on Day 1.

Triamcinolone acetonide 40 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (75)

Pinnacle Research Group, LLC

Anniston, Alabama, 36207-5710, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Associated Pharmaceutical Research

Buena Park, California, 90620, United States

Location

Northern California Institute for Bone Health

Oakland, California, 94609, United States

Location

San Diego Arthritis & Osteoporosis Medical Clinic

San Diego, California, 92108, United States

Location

Center for Clinical Trials of San Gabriel

West Covina, California, 91790, United States

Location

Tampa Medical Group, P.A.

Tampa, Florida, 33614, United States

Location

Florida Medical Clinic, PA

Zephyrhills, Florida, 33542, United States

Location

Harbin Clinic

Rome, Georgia, 30165, United States

Location

Intermountain Orthopedics

Boise, Idaho, 83702, United States

Location

Northwest Clinical Trials

Boise, Idaho, 83704, United States

Location

The Arthritis Center

Springfield, Illinois, 62704, United States

Location

Cotton O'Neil Clinic

Topeka, Kansas, 66606, United States

Location

Arthritis and Diabetes Clinic

Monroe, Louisiana, 71203, United States

Location

Arthritis Consultants, Inc.

St Louis, Missouri, 63141, United States

Location

Billings Clinic Research Center

Billings, Montana, 59101, United States

Location

Montana Medical Research

Missoula, Montana, 59804, United States

Location

Heartland Clinical Research, Inc.

Omaha, Nebraska, 68134, United States

Location

New Mexico Clinical Research & Osteoporosis Center, Inc.

Albuquerque, New Mexico, 87106, United States

Location

Regional Clinical Research Rheumatology Assoc.

Binghamton, New York, 13905, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Community Research Partners, Inc.

Varnville, South Carolina, 29944, United States

Location

Comprehensive Rheumatology

Hendersonville, Tennessee, 37075, United States

Location

MultiSpecialty Clinical Research

Johnson City, Tennessee, 37601, United States

Location

Integrity Clinical Research, LLC

Milan, Tennessee, 38358, United States

Location

Southwest Rheumatology

Mesquite, Texas, 75150, United States

Location

Health Research of Hampton Roads

Newport News, Virginia, 23606, United States

Location

Novartis Investigative site

Rosario, Argentina

Location

Novartis Investigative site

Gozée, Belgium

Location

Novartis Investigative site

Moncton, Canada

Location

Novartis Investigative site

Mount Pearl, Canada

Location

Novartis Investigative site

St. John's, Canada

Location

Novartis Investigative site

Paris, France

Location

Novartis Investigative Site

Bad Nauheim, Germany

Location

Novartis Investigative Site

Bautzen, Germany

Location

Novartis Investigative Site

Berlin, Germany

Location

Novartis Investigative Site

Chemnitz, Germany

Location

Novartis Investigative Site

Dachau, Germany

Location

Novartis Investigative Site

Dresden, Germany

Location

Novartis Investigative Site

Frankfurt, Germany

Location

Novartis Investigative Site

Georgensgmünd, Germany

Location

Novartis Investigative Site

Hamburg, Germany

Location

Novartis Investigative Site

Leipzig, Germany

Location

Novartis Investigative Site

Löhne, Germany

Location

Novartis Investigative Site

Magdeburg, Germany

Location

Novartis Investigative Site

Messkirch, Germany

Location

Novartis Investigative Site

Munich, Germany

Location

Novartis Investigative Site

Schwabach, Germany

Location

Novartis Investigative Site

Zerbst, Germany

Location

Novartis Investigative site

Poznan, Poland

Location

Novartis Investigative site

Szczecin, Poland

Location

Novartis Investigative site

Wroclaw, Poland

Location

Novartis Investigative site

Chelyabinsk, Russia

Location

Novartis Investigative Site

Moscow, Russia

Location

Novartis Investigative Site

Saint Petersburg, Russia

Location

Novartis Investigative site

Tyumen, Russia

Location

Novartis Investigative Site

Yaroslavl, Russia

Location

Novartis Investigative site

Yekaterinburg, Russia

Location

Novartis Investigative site

Baden, Switzerland

Location

Novartis Investigative site

Basel, Switzerland

Location

Novartis Investigative site

Bern, Switzerland

Location

Novartis Investigative site

Lausanne, Switzerland

Location

Novartis Investigative Site

Adana, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, Turkey (Türkiye)

Location

Novartis Investigative Site

Antalya, Turkey (Türkiye)

Location

Novartis Investigative Site

Aydin, Turkey (Türkiye)

Location

Novartis Investigative Site

Gaziantep, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, Turkey (Türkiye)

Location

Novartis Investigative Site

Manisa, Turkey (Türkiye)

Location

Novartis Investigative site

Sihhiye/Ankara, Turkey (Türkiye)

Location

Novartis Investigative Site

Antrim, United Kingdom

Location

Novartis Investigative Site

Coventry, United Kingdom

Location

Novartis Investigative Site

Lancashire, United Kingdom

Location

Novartis Investigative Site

Wellingborough, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 24122883 DERIVED

• Schlesinger N, De Meulemeester M, Pikhlak A, Yucel 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. doi: 10.1186/ar3297.

  PMID: 21439048 DERIVED

• So A, De Meulemeester M, Pikhlak A, Yucel 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. doi: 10.1002/art.27600.

  PMID: 20533546 DERIVED

MeSH Terms

Conditions

Gout

Interventions

canakinumab; Triamcinolone Acetonide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 25, 2008
• First Posted: November 26, 2008
• Study Start: November 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: April 10, 2012
• Results First Posted: May 16, 2011

Record last verified: 2012-04

Locations

TU (9); DE (16); US (27); GB (4); AR (1); CA (3); BE (1); FR (1); RU (6); PL (3); CH (4)