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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00798369
First received: November 25, 2008
Last updated: April 9, 2012
Last verified: April 2012

November 25, 2008
April 9, 2012
November 2008
August 2009   (final data collection date for primary outcome measure)
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).
The dose of ACZ885 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 VAS [ Time Frame: at 72 hours post-dose ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00798369 on ClinicalTrials.gov Archive Site
  • 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.
  • The change in pain intensity in the target joint following ACZ885 administration compared to triamcinolone acetonide on Visual Analog Scale and via a 5-point Likert scale [ Time Frame: at 6, 12, 24, 48, 72 hours post-dose and 4, 5, 6, 7 days post-dose ] [ Designated as safety issue: No ]
  • The efficacy of ACZ885 as compare to triamcinolone acetonide with regards to the patient`s global assessment of response to treatment [ Time Frame: at 72 hours and 7 days post-dose ] [ Designated as safety issue: No ]
  • The efficacy of ACZ885 as compare to triamcinolone acetonide with regards to the time to 50% reduction of baseline pain intensity in the target joint [ Time Frame: within 7 days after randomization ] [ Designated as safety issue: No ]
  • The efficacy of ACZ885 as compare to triamcinolone acetonide with regards to the high sensitivity C-reactive protein and serum amyloid protein levels [ Time Frame: at 72 hours and 7 days, 4 and 8 weeks post-dose ] [ Designated as safety issue: No ]
  • The efficacy of ACZ885 as compare to triamcinolone acetonide with regards to the amount of rescue medication taken [ Time Frame: 7 days after study drug administration ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Targeted Dose Finding of Canakinumab (ACZ885) for Management of Acute Flare in Refractory or Contraindicated Gout Patients
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Acute Gout
  • 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.
  • 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.
  • Drug: Triamcinolone acetonide
    Randomized patients received triamcinolone acetonide 40 mg i.m. once and placebo matching canakinumab s.c. once, on Day 1.
  • 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.
    Intervention: Drug: Canakinumab
  • 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.
    Intervention: Drug: Canakinumab
  • 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.
    Intervention: Drug: Canakinumab
  • 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.
    Intervention: Drug: Canakinumab
  • 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.
    Intervention: Drug: Canakinumab
  • 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.
    Intervention: Drug: Triamcinolone acetonide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
200
August 2009
August 2009   (final data collection date for primary outcome measure)

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

Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Poland,   Turkey,   United Kingdom,   Argentina,   Belgium,   Canada,   France,   Germany,   Russian Federation,   Switzerland
 
NCT00798369
CACZ885H2255, EudraCT 2008-004666-61
Not Provided
External Affairs, Novartis Pharmaceuticals
Novartis
Not Provided
Not Provided
Novartis
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP