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

Acute Gout Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00798369
• Other study ID #: CACZ885H2255
• Secondary ID: EudraCT 2008-004
• Status: Completed
• Phase: Phase 2
• First received: November 25, 2008
• Last updated: April 9, 2012
• Start date: November 2008
• Est. completion date: August 2009

Study information

• Verified date: April 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Pharmacological Committee, Ministry of HealthSwitzerland: Federal Office of Public HealthTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Gout
• Gout

Intervention

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

Locations

Country	Name	City	State
Argentina	Novartis Investigative site	Rosario
Belgium	Novartis Investigative site	Gozée
Canada	Novartis Investigative site	Moncton
Canada	Novartis Investigative site	Mount Pearl
Canada	Novartis Investigative site	St. John's
France	Novartis Investigative site	Paris cedex 10
Germany	Novartis Investigative Site	Bad Nauheim
Germany	Novartis Investigative Site	Bautzen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Dachau
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Georgensgmuend
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Loehne
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Messkirch
Germany	Novartis Investigative Site	Munich
Germany	Novartis Investigative Site	Schwabach
Germany	Novartis Investigative Site	Zerbst
Poland	Novartis Investigative site	Poznan
Poland	Novartis Investigative site	Szczecin
Poland	Novartis Investigative site	Wroclaw
Russian Federation	Novartis Investigative site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative site	Tyumen
Russian Federation	Novartis Investigative Site	Yaroslavl
Russian Federation	Novartis Investigative site	Yekaterinburg
Switzerland	Novartis Investigative site	Baden
Switzerland	Novartis Investigative site	Basel
Switzerland	Novartis Investigative site	Bern
Switzerland	Novartis Investigative site	Lausanne
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Antalya
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Gaziantep
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Manisa
Turkey	Novartis Investigative site	Sihhiye/Ankara
United Kingdom	Novartis Investigative Site	Antrim
United Kingdom	Novartis Investigative Site	Coventry
United Kingdom	Novartis Investigative Site	Lancashire
United Kingdom	Novartis Investigative Site	Wellingborough
United States	New Mexico Clinical Research & Osteoporosis Center, Inc.	Albuquerque	New Mexico
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	Billings Clinic Research Center	Billings	Montana
United States	Regional Clinical Research Rheumatology Assoc.	Binghamton	New York
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Intermountain Orthopedics	Boise	Idaho
United States	Northwest Clinical Trials	Boise	Idaho
United States	Associated Pharmaceutical Research	Buena Park	California
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Comprehensive Rheumatology	Hendersonville	Tennessee
United States	MultiSpecialty Clinical Research	Johnson City	Tennessee
United States	Southwest Rheumatology	Mesquite	Texas
United States	Integrity Clinical Research, LLC	Milan	Tennessee
United States	Montana Medical Research	Missoula	Montana
United States	Arthritis and Diabetes Clinic	Monroe	Louisiana
United States	Health Research of Hampton Roads	Newport News	Virginia
United States	Northern California Institute for Bone Health	Oakland	California
United States	Heartland Clinical Research, Inc.	Omaha	Nebraska
United States	Harbin Clinic	Rome	Georgia
United States	San Diego Arthritis & Osteoporosis Medical Clinic	San Diego	California
United States	The Arthritis Center	Springfield	Illinois
United States	Arthritis Consultants, Inc.	St. Louis	Missouri
United States	Tampa Medical Group, P.A.	Tampa	Florida
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	Community Research Partners, Inc.	Varnville	South Carolina
United States	Center for Clinical Trials of San Gabriel	West Covina	California
United States	Florida Medical Clinic, PA	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  France,  Germany,  Poland,  Russian Federation,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide	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).	Baseline,at 72 hrs post-dose and 7 days post-dose	No
Secondary	Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment	Participants scored their global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Slight and Poor.	at 72 hours post-baseline	No
Secondary	The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint	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).	Baseline, within 7 days after randomization	No
Secondary	High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group	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.	at 72 hours and 7 days, 4 and 8 weeks post-dose	No
Secondary	Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group	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.	at 72 hours and 7 days, 4 and 8 weeks post-dose	No
Secondary	Amount of Rescue Medication Taken for Each Treatment Group	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.	7 days after study drug administration	No