Targeted Dose Finding of Canakinumab (ACZ885) for Management of Acute Flare in Refractory or Contraindicated Gout Patients
- Registration Number
- NCT00798369
- Lead Sponsor
- Novartis
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 200
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Canakinumab 10 mg Canakinumab 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. Canakinumab 150 mg Canakinumab 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. Triamcinolone acetonide 40 mg Triamcinolone acetonide 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. Canakinumab 50 mg Canakinumab 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. Canakinumab 25 mg Canakinumab 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. Canakinumab 90 mg Canakinumab 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.
- Primary Outcome Measures
Name Time Method 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) at 24,48 and 72 hours post-baseline 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
Name Time Method 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 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 at 72 hours post-baseline 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 Baseline, within 7 days after randomization 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 at 72 hours and 7 days, 4 and 8 weeks post-dose 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 at 72 hours and 7 days, 4 and 8 weeks post-dose 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 7 days after study drug administration 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.
Trial Locations
- Locations (29)
Montana Medical Research
🇺🇸Missoula, Montana, United States
Northwest Clinical Trials
🇺🇸Boise, Idaho, United States
Novartis Investigative Site
🇬🇧Wellingborough, United Kingdom
Harbin Clinic
🇺🇸Rome, Georgia, United States
Tampa Medical Group, P.A.
🇺🇸Tampa, Florida, United States
The Arthritis Center
🇺🇸Springfield, Illinois, United States
Cotton O'Neil Clinic
🇺🇸Topeka, Kansas, United States
Comprehensive Rheumatology
🇺🇸Hendersonville, Tennessee, United States
Arthritis Consultants, Inc.
🇺🇸St. Louis, Missouri, United States
San Diego Arthritis & Osteoporosis Medical Clinic
🇺🇸San Diego, California, United States
Florida Medical Clinic, PA
🇺🇸Zephyrhills, Florida, United States
Billings Clinic Research Center
🇺🇸Billings, Montana, United States
Regional Clinical Research Rheumatology Assoc.
🇺🇸Binghamton, New York, United States
Intermountain Orthopedics
🇺🇸Boise, Idaho, United States
Novartis Investigative site
🇹🇷Sihhiye/Ankara, Turkey
Pinnacle Research Group, LLC
🇺🇸Anniston, Alabama, United States
Northern California Institute for Bone Health
🇺🇸Oakland, California, United States
Southwest Rheumatology
🇺🇸Mesquite, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Associated Pharmaceutical Research
🇺🇸Buena Park, California, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
New Mexico Clinical Research & Osteoporosis Center, Inc.
🇺🇸Albuquerque, New Mexico, United States
Center for Clinical Trials of San Gabriel
🇺🇸West Covina, California, United States
Arthritis and Diabetes Clinic
🇺🇸Monroe, Louisiana, United States
Heartland Clinical Research, Inc.
🇺🇸Omaha, Nebraska, United States
Community Research Partners, Inc.
🇺🇸Varnville, South Carolina, United States
MultiSpecialty Clinical Research
🇺🇸Johnson City, Tennessee, United States
Integrity Clinical Research, LLC
🇺🇸Milan, Tennessee, United States
Health Research of Hampton Roads
🇺🇸Newport News, Virginia, United States